1 Introduction
Sulfur oxides of divalent sulfur occupy an important position in organic sulfur chemistry. Sulfones and sulfoxides, as well as sulfonamides and sulfinamides, are often used in organic synthesis as building blocks or synthesis AIDS for biologically active compounds
[1,2]. Correspondingly, the reaction of S-dioxides of thiocarbonyl compounds (thiones), namely olefinic sulfones, has also been studied in depth
[3]. In this process, our group deeply studied the reactivity of vinyl sulfone, such as the reaction mechanism of vinyl sulfone generated by elimination of sulfonyl chloride and imine to synthesize β-sultam, the selectivity of cyclization and the stereoselectivity of its products, and also studied the reaction of vinyl sulphone with different cyclic imines
[4][5⇓⇓~8][5,6,9,10][11]. In addition, Peters' group has also studied the asymmetric reaction of sulfonyl chloride with electron-deficient imines and aldehydes to synthesize optically active β-sultam and β-sultone
[12,13]. In addition to the reaction of vinyl sulfones, the reaction of phosphinoketones with similar structures to vinyl sulfones has also been studied, which can also undergo cyclization with aldehydes, ketones and imines to produce phosphonolactones and lactam derivatives
[14⇓⇓⇓~18]. Olefin sulfoxides, which are structurally similar to olefin sulfones, have also been extensively studied, and sulfur center heterodienes, which can be represented by the general formula X (Y) C = S = O, are called olefin sulfoxides. Originally prepared and named by Sheppard and Diekmann, vinyl sulfoxide is also known as thiocarbonyl S-monoxide to distinguish it from the unstable active compound thiocarbonyl S-dioxide (vinyl sulfone), which has a similar structure
[19]. There are relatively few examples of alkene sulfoxides occurring as single compounds in natural products. For example, the ethyl olefin sulfoxide in onion is the main factor leading to its lacrimation
[20]. In addition, it has been reported that olefin sulfoxides are key intermediates in the metabolism of synthetic drugs
[21]. The first stable vinyl sulfoxide that could be isolated was obtained by Wedekind et al. In 1923 by treating camphor-10-sulfonyl chloride with pyridine or triethylamine
[22]. However, its precise structure was determined 40 years later by King and Durst through spectral analysis
[23].
The structure of olefin sulfoxide can be formally considered as replacing an O atom in SO
2 with a C atom, and then it is speculated that the structure of olefin sulfoxide is similar to that of SO
2. In contrast to the SO
2, the S atom of both enesulfoxide and triplet SO
2 has a lone pair of electrons, which makes both nonlinear. However, there is also a singlet form of SO
2, that is, after the SO
2 is excited to the active state, the electrons can be transferred to the empty orbital, and then the diradical form, which is not found in olefin sulfoxide compounds
[24]. The nonlinear structure of olefin sulfoxide has been determined by dipole moment measurement, 1H NMR analysis and XRD single crystal diffraction
[25][26][27]. Therefore, the olefin sulfoxides X (Y) C = S = O of X X Y have cis-trans stereoisomers, which can be generally divided into E- and Z-isomers. The stability of olefin sulfoxides depends on their substituent species. Aryl-substituted ene sulfoxides are more stable than their aliphatic counterparts. Aliphatic substituted ene sulfoxides are readily decomposed at very low temperatures, although they can also be isolated by suitable methods. When the carbon atom of the olefin sulfoxide is directly connected with a heteroatom, such as Cl, S, SO, SO
2, P, NHR, its stability can be increased
[28].
Olefin sulfoxide compounds are generally prepared by oxidation of thiocarbonyl compounds. Sulfinyl derivatives β-elimination of readily leaving groups (halogen, trichloromethyl, methoxy, etc.) and re-elimination of sulfinylation of compounds containing active methylene groups. Alkenyl sulfoxides can also be obtained by the modified Peterson oxidation reaction, in which the α-silyl carbanion reacts with SO2 followed by elimination. Heteroatom-Wolff rearrangement of α-sulfinyl diazo compounds. In addition, there are some uncommon methods, such as allyl vinyl sulfoxide compound rearrangement or retro-Diels-Alder reaction, which can also obtain vinyl sulfoxide compounds.
For olefin sulfoxide, according to the resonance formula of its structure, it can be found that the O atom is electronegative and the S and C atoms are electropositive (Fig. 1). Therefore, the olefin sulfoxide can either be attacked by other nucleophiles to undergo a nucleophilic type addition reaction or act as a nucleophile to attack other electrophiles to undergo an electrophilic type reaction. In addition, vinyl sulfoxides can also act as dienophiles to undergo [4 + 2] Diels-Alder reactions, and acyl or alkenyl-substituted vinyl sulfoxides can act as dienophiles to undergo [4 + 2] Diels-Alder reactions with reverse electron requirements. And the ene sulfoxide can also act as a dipolarophile to undergo dipolar cycloaddition reactions with other 1,3-dipolarophiles, and itself can also act as a 1,3-dipole to undergo dipolar cycloaddition reactions with other dipolarophiles. Due to the high activity of olefin sulfoxide itself, it is easy to dimerize or desulfurize.
2 Synthesis and Preparation of Olefin Sulfoxide
2.1 Oxidation of thiocarbonyl compound
2.1.1 Hydrogen peroxide oxidation
The oxidation of thiocarbonyl compounds to prepare olefin sulfoxides is an early and widely used method for the preparation of olefin sulfoxides. As early as 1938, Kitamura reported the reaction of thiourea under hydrogen peroxide oxidation, and its structure was speculated to be imine sulfenic acid at that time
[29]. It was not until 1960, when Walter studied it again, that the correct structure of the product obtained from the oxidation of thioamide 1 by hydrogen peroxide was determined to be thioamide S-oxide, that is, amino ene sulfoxide, and it was speculated that the reason for the relatively stable structure of product 2 was the formation of intramolecular hydrogen bonds (Scheme 1)
[30].
The oxidation of thiocarbonyl compounds is a very efficient method for the preparation of olefin sulfoxides. Most of them use peracids as oxidants, which can be divided into thione oxidation, xanthate oxidation, dithiocarboxylate oxidation, dithiocarbamate oxidation and trithiocarbonate oxidation according to the types of raw thiocarbonyl compounds (Figure 2)
[31][32][33][34][35].
2.2 Preparation of olefin sulfoxides by β-elimination of sulfinyl derivatives
2.2.1 Sulfinyl chloride elimination to prepare olefin sulfoxide
In 1964, Diekmann's group reported that fluorenyl sulfoxide 4 was obtained from fluorenylsulfinyl chloride 3 in the presence of triethylamine as a base, and its structure was determined by NMR, IR and MS
[19]. For aliphatic isopropylsulfinyl chloride 5, dimethyl sulfoxide 6 can also be formed under triethylamine conditions (Scheme 2-1). Soon after, Zwanenburg et al. Used this method to prepare the brilliant yellow thioaldehyde S-oxidation product (2-methoxynaphthalen-1-yl) ene sulfoxide 7 (Scheme 2-2)
[36].
2.2.2 Preparation of vinyl sulfoxides by β-elimination of chloroform from trichloromethyl sulfoxide
Braverman's group reported that allyl or benzyl trichloromethyl sulfoxide β-eliminates chloroform to give monosubstituted alkenyl sulfoxides
[37]. Mechanistic studies have shown that the elimination reaction is mainly a stepwise reversible E1cb-type elimination, rather than a concerted E2-type elimination. Because in the mechanistic study experiment, it was found that the rate of H-D exchange was faster than that of olefin sulfoxide formation when cinnamyl trichloromethyl sulfoxide was treated with triethylamine in the presence of D
2O (Scheme 3).
2.2.3 Preparation of olefin sulfoxides by elimination of methyl diarylmethylsulfinate
Kice et al. Studied the base-induced elimination of methyl diarylmethylsulfinate 8 to give a series of olefin sulfoxide products 9, and used deuterium experiments to prove that the elimination reaction of sulfinate was faster than the nucleophilic substitution reaction at the sulfinyl group during the reaction
[38]. The yield of olefin sulfoxide obtained by this method is 70% ~ 80% (Figure 4).
2.2.4 Preparation of olefin sulfoxides by β-elimination of aromatic heterocycle
Morita's group selected β-carbonyl sulfinyl heteroaromatic ring (tetrazole, triazole, thiadiazole) compounds 10 as ene sulfoxide precursors, which underwent pyrolysis elimination to produce acyl ene sulfoxides, and the formation of ene sulfoxide intermediates was proved by the capture of 2,3-dimethylbuta-1,3-diene to obtain 6-substituted-5,6-dihydro-3,4-dimethyl-2H-thiopyran-1-oxide 11 (Scheme 5)
[39].
2.2.5 Sulfinylation and β-elimination of active methylene compounds
Olefin sulfoxide compounds can be prepared by reacting a compound containing active methylene with thionyl chloride under alkaline conditions. On the basis of Oka et al.'s Research on the reaction of compounds containing active methylene groups with thionyl chloride, Hull's group reported that the reaction of dihydrothiophenone with thionyl chloride in dimethoxyethane gave a yellow needle-like olefin sulfoxide product in 91% yield
[40][41]. However, due to the high activity of the olefin sulfoxide compound, it is easy to decompose in dimethyl sulfoxide, and its NMR data can not be obtained. Only through the comparison of elemental analysis, mass spectrometry and infrared characteristic peaks, the structure of the olefin sulfoxide compound can be obtained (Figure 6). Since the NMR data of the olefin sulfoxide product was not available in this work, Zwanenburg et al. Repeated the work of Oka and Hull, using 2,3-dimethylbuta-1,3-diene to capture the formed olefin sulfoxide, and indirectly proved the formation of the olefin sulfoxide compound by determining the single crystal structure of the cycloaddition product
[42][41].
In addition to using dihydrothiophenone as an active methylene-containing compound as an olefin sulfoxide precursor, Zwanenburg's group has also studied other active methylene-containing compounds as olefin sulfoxide precursors
[43]. In these reactions, the addition of a base is not necessary for ketones that can be enolized well. However, if this is not the case, triethylamine or 2,6-lutidine is added as a base to initiate the reaction. In addition, the enol structure is fixed in the form of silyl enol ether, which is used to react with thionyl chloride to form sulfinyl chloride, and then eliminated to obtain α-oxoalkene sulfoxide compounds (Table 1).
Black et al. Reported that γ-nitroketone 12 could be used as a precursor of olefin sulfoxide to prepare olefin sulfoxide 13 by reaction with thionyl chloride, and designed different types of reaction substrates
[44]. According to the results of the reaction, the presence of the nitro group was considered to play a decisive role in the formation of this type of ene sulfoxide, and the key intermediate was identified by NMR spectroscopy (Scheme 7).
Bergman et al. Also obtained olefin sulfoxide compound 15 by the reaction of indolylalkanone 14 with thionyl chloride
[45]. Using acetonitrile as solvent, indolidinone reacts with thionyl chloride at 30 ~ 35 ℃ to obtain intermediate sulfinyl chloride, and one molecule of hydrogen chloride is quickly removed to obtain α-oxoalkene sulfoxide (Figure 8).
In addition to compounds with an active methylene group in the presence of a carbonyl group at the α-position, which can be used as olefin sulfoxide precursors, compounds with an active methylene group in the presence of a cyano group at the α-position have also been reported as olefin sulfoxide precursors. Ohoka et al. Found that phenylacetonitrile could react with thionyl chloride in the presence of trace HCl to obtain 5% olefin sulfoxide compound, which was characterized by infrared spectroscopy, elemental analysis and nuclear magnetic resonance spectroscopy
[46]. In the infrared spectrum, the characteristic peak positions of C = S = O are at 1140 and 998 cm
-1.
In addition, there are some reports on the preparation of olefin sulfoxides by elimination reaction. As reported by Menichetti's group, in the presence of a catalytic amount of pyridine, the sulfinamide can be eliminated to give an α-oxoalkene sulfoxide, which is captured by the 2,3-dimethylbuta-1,3-diene present in the system to give a dihydrothiopyran compound
[47]. The method is simple and practical, and alkyl, aryl and heteroaryl substituted thiophthalimides can be well reacted.
2.3 Modified Peterson oxidation
Zwanenburg et al. First developed the use of a more active phosphorus ylide to react with sulfur dioxide to remove a molecule of triphenylphosphine oxide through a four-membered ring transition state through a Wittig type reaction and produce the corresponding olefin sulfoxide compound (Figure 9)
[48]. On the basis of this work, the research group started from compound 16 containing methylene, and reacted with trimethylchlorosilane to obtain the corresponding silane compound.After treatment with strong base n-butyllithium or lithium diisopropylamide, excess sulfur dioxide was introduced to remove trimethylsilica through Peterson reaction to obtain the corresponding olefin sulfoxide compound 17 (fig. 10)
[49]. In this process, the control of reaction temperature plays an important role in the formation of anions in the system and the reaction rate with SO
2. In addition, excess SO
2 also plays an important role in the elimination of trimethyl silica to form vinyl sulfoxide.
In addition, a suitable nucleophile was selected in this work, and the β-addition of vinylsilane 18 occurred, and then the newly formed α-silyl carbanion underwent a similar process, that is, the reaction with SO
2 followed by the removal of trimethylsilica could also give the olefin sulfoxide product 19 (Figure 11)
[49].
2.4 Preparation of vinyl sulfoxides by Wolff rearrangement
Enones can be obtained from α-carbonyl diazo compounds via Wolff rearrangement, while α-sulfoxide diazo compounds or other carbene precursors can also be obtained via Wolff rearrangement. In 1979, Franck-Neumann et al. First reported that the corresponding olefin sulfoxide product could be obtained by Wolff rearrangement of vinyl sulfoxide carbene obtained from 5-sulfoxyl-3,3-dimethylpyrazole by removing nitrogen under illumination (Figure 12)
[50].
Rosati et al. Also reported that 2-diazosulfoxide compounds prepared from cephalosporins were subjected to heteroatom-Wolff rearrangement by irradiation to obtain ene sulfoxide intermediates, and carbapenem ring compounds were obtained by further irradiation-induced desulfurization
[51]. Unfortunately, they failed to isolate the intermediate olefin sulfoxide, probably due to its high activity.
Until 1998, Maguire et al. Developed a series of relatively stable α-diazo-β-oxo sulfoxide cyclic compounds by analyzing the molecular structure of diazosulfoxide compounds containing cephalosporin compound skeleton, which were assembled by Rosati
[52][51]. On this basis, the decomposition reaction of α-diazosulfoxide compounds catalyzed by rhodium was studied, and it was found that α-diazosulfoxide compounds could be rearranged to olefin sulfoxide compounds catalyzed by rhodium, and the corresponding six-membered ring products could be obtained by using the active olefin sulfoxide generated in the 2,3-dimethylbuta-1,3-diene or cyclopentadiene capture system (Figure 13)
[53].
In 2008, Rosati's team found that olefin sulfoxide compounds could also be obtained by microwave irradiation of α-diazo-β-oxo sulfoxide cyclic compounds, and the olefin sulfoxide was captured by 2,3-dimethylbuta-1,3-diene, and the stereoconfiguration of the product was analyzed.It was found that after microwave irradiation, the diazosulfoxide underwent heteroatom-Wolff rearrangement, and the kinetic product of Z-configuration vinyl sulfoxide was obtained first, and with the change of time, the kinetic product would gradually transform into E-configuration vinyl sulfoxide with more thermodynamic stability
[54].
Developed by Aitken et al., the sulfoxide stabilized phosphorus ylide 20 reacts under flash vacuum pyrolysis (FVP) conditions to remove triphenylphosphine to obtain sulfoxide carbene, and after further Wolff rearrangement, olefin sulfoxide 21 can be obtained.In addition, the olefin sulfoxide compound further undergoes 1,2-oxygen migration and desulfurization under the reaction conditions to form a ketone compound 22, and the formation of the olefin sulfoxide during the reaction is proved by the detection of the ketone compound 22 (Figure 14)
[55].
2.5 Other methods for preparing olefin sulfoxide
In addition to the methods mentioned above for the preparation of olefin sulfoxides, there are some methods that are not very common.
2.5.1 Allyl vinyl sulfoxide compound rearrangement
In 1985, Block et al. Proposed that the sulfoxide compound obtained from the oxidation of allyl vinyl sulfide 23 was rearranged via thia-Claisen [3,3] sigmatropic migration to form homoallylic ene sulfoxide compound 24 (Scheme 15)
[56].
After that, Baudin et al. Used allyl Grignard reagent to undergo addition substitution with vinyl sulfinate to obtain allyl vinyl sulfoxide compound, and soon underwent similar [3,3] sigmatropic rearrangement to obtain γ-unsaturated substituted vinyl sulfoxide product (Scheme 16)
[57].
2.5.2 Synthesis of vinyl sulfoxides by retro-Diels-Alder reaction
Capozzi's group started from 1,4-oxathiocyclohexene, which was produced by the reverse electron demand Diels-Alder reaction of α, α '-dioxothione with electron-rich dienophile enol ether or activated styrene, and oxidized it to the corresponding sulfoxide compound, followed by the reverse Diels-Alder reaction to remove a molecule of alkenyl alkyl ether and obtain α, α' -dioxene sulfoxide compound
[55]. The generated olefin sulfoxide can be used as an electron-deficient diene to be captured by a dienophile to generate [4 + 2] 1,4-oxathiane-S-oxide, and can also be used as a dienophile to react with the diene to obtain [4 + 2] dihydrothiopyrane-S-oxide (Scheme 17).
3 Olefin sulfoxide reaction
There are many reports on the reaction of olefin sulfoxide, such as the carbonophilic or thiophilic attack of nucleophilic reagent on olefin sulfoxide, the reaction of olefin sulfoxide as nucleophilic reagent with other electrophilic reagents, Diels-Alder cycloaddition, 1,3-dipolar cycloaddition, etc. In addition, olefin sulfoxide itself can also undergo desulfurization, deoxygenation, dimerization and other reactions, which are described in detail below.
3.1 Olefin sulfoxide autoreaction
3.1.1 Olefin sulfoxide desulfurization to carbonyl compound
Desulfurization of olefin sulfoxides can proceed via several different reaction pathways. Schlessinger et al. Found that fluorenyl sulfoxide 25 can first generate fluorenylmethyl sulfoxide anion 26 under the attack of methyl lithium reagent, and then attack another molecule of fluorenyl sulfoxide 25.The resulting intermediate 27 is stripped of a molecule of dimethyl sulfoxide under the action of methyllithium to form a sulfoxide dianion 28 followed by thiirane, which can be desulfurized under the action of methyllithium to form an olefin 29 (Scheme 18)
[59].
King and Durst synthesized chloro (phenyl) ene sulfoxides. In order to study their properties, they found that these ene sulfoxides could be desulfurized to benzoyl chloride by ultraviolet irradiation
[25]. Subsequently, Zwanenburg et al. Obtained the desulfurization product (2-methoxynaphthalen-1-yl) formaldehyde and sulfur by irradiating (2-methoxynaphthalen-1-yl) ene sulfoxide
[36].
Schlessinger and Schultz used a variety of characterization methods to study the photolysis mechanism of olefin sulfoxides, and considered that the difference in the concentration of the reaction system would lead to two different reaction pathways: in relatively dilute chloroform or benzene solutions, the reaction involved a unimolecular oxathiocyclopropane process
[60]; In higher concentrations, there is evidence of photodimer formation followed by decomposition to ketones. However, the structure of the dimer in this process has not been well determined. It is worth noting that Holm et al. Used electronic absorption spectroscopy and phosphorescence spectroscopy to confirm the existence of oxathiirane in the diphenyl ene sulfoxide reaction at 85 K and under illumination
[61].
Karlstroem and Carlsen, in their study of the photocatalytic formation and decomposition of oxathiiranes, used theoretical calculations to propose that olefin sulfoxides first rearrange to oxathiiranes under photocatalysis,Then, under photocatalysis, the oxygen-sulfur bond undergoes homolytic cleavage to form a singlet diradical intermediate, which undergoes vibrational relaxation to remove the sulfur atom to form the corresponding carbonyl compound (Figure 19)
[62].
After that, Mloston and Schreiner et al. analyzed the decomposition products of thioformaldehyde sulfoxide (monosubstituted olefin sulfoxide) under irradiation, and compared the experimental infrared spectra with the theoretical simulated infrared spectra to confirm the formation of oxathiridine compounds in the decomposition products of the olefin sulfoxide
[63]. In order to further explore the desulfurization mechanism of olefin sulfoxide under illumination, they used infrared and calculation to study the decomposition of olefin sulfoxide in argon system in detail. The results show that the olefin sulfoxide first rearranges to oxathiirane at low temperature and under light irradiation, but it is different from the diradical intermediate process. It is found that the desulfurization of oxathiirane is mainly through the bimolecular process, and the activation enthalpy of this process is close to 0 kcal/mol. In the case of 3,3-dimethyloxathiirane, for example, two molecules of oxathiirane interact to form a new S — S bond and remove one molecule of acetone, which is then cleaved to give another molecule of acetone and S
2 (Fig. 3)
[64].
Mart Martínez and Curchod et al. Reported the study on the photodecomposition reaction of sulfoxides in 2016. Through a large number of in-depth calculation studies on the excited state dynamics in the reaction, it was speculated that the non-thermal ground state reaction caused by the conversion of high-energy photons into vibrational energy after electronic transition was the reason for the diversity of photodecomposition products of sulfoxides
[65]. In addition to the studies on the photodecomposition of olefin sulfoxides, there are also some reports on the thermal decomposition of olefin sulfoxides. Carlsen and Stilkerieg et al. Studied the decomposition of diphenyl sulfoxide in argon atmosphere at 130 ℃ in the absence of light, and considered that the process could occur through both monomolecular and bimolecular pathways: for monomolecular reaction, oxathiirane was first rearranged into oxathiirane under argon condition, and then desulfurization occurred; For the bimolecular reaction, it is likely that the dimer “(PhCSO)
2” is formed first from two molecules of olefin sulfoxide under argon condition, and then the dimer is decomposed. However, no evidence has been found to prove this process. In addition, it was found that the desulfurization reaction was more likely to occur in oxygen atmosphere. First, the olefin sulfoxide was oxidized by molecular oxygen to form the intermediate “Ph
2CSO
3”, which was decomposed to form the desulfurization products benzophenone and sulfur dioxide. In addition, at higher temperatures, the olefin sulfoxide can first decompose to give a carbene intermediate, which then reacts with the resulting SO, but there is no conclusive experimental evidence for this process (Scheme 20)
[66].
Metzner et al., in the study of the oxidation of thione with m-chloroperbenzoic acid to prepare the corresponding olefin sulfoxide, placed the relatively stable olefin sulfoxide product at room temperature for several days.The formation of elemental sulfur can be observed, and it is considered that this process starts from the olefin sulfoxide and undergoes a thermodynamically allowed electrocyclization reaction to obtain the oxathiirane, followed by the extrusion of elemental sulfur to obtain the corresponding carbonyl compound
[67]. In addition, Adam et al. Used the oxathiirane intermediate produced in the olefin sulfoxide desulfurization process as a sulfur source to realize the direct ring sulfurization of tensional cycloolefins, which not only verified the olefin sulfoxide desulfurization mechanism, but also provided a new method for the synthesis of thiiranes (Figure 21)
[68].
Different from the desulfurization under irradiation or heating conditions mentioned above, Block can also obtain the desulfurized enal product by reacting the prepared enal S-oxide (alkenyl monosubstituted olefin sulfoxide) with HgO/BF
3·Et
2O at room temperature for 30 min
[56].
3.2 Reaction of olefin sulfoxides with nucleophiles
Olefin sulfoxides act as both electrophiles and nucleophiles. Because of its structure, nucleophilic reactions at different positions on the sulfur and carbon atoms of the alkene sulfoxide can occur. In general, the nucleophile mainly attacks the sulfur atom site, while when Z is an easy leaving group, the nucleophilic substitution reaction to the carbon atom site can occur (Scheme 22).
3.2.1 Nucleophilic reaction occurring at the sulfur atom of an alkene sulfoxide
3.2.1.1 Reaction of alkali-metal organic reagents as thiophilic reagents
Schlessinger et al. Found that methyl lithium or phenyl lithium reagents can nucleophilically attack the sulfur atom in diaryl ene sulfoxides and undergo addition reactions to obtain the corresponding alkyl sulfoxide compounds in good yields
[59]. When Venier et al studied the reaction of dihalocarbene with diaryl olefin sulfoxide, they found that the trichloromethyl anion generated by the thermal decomposition of sodium trichloroacetate could directly attack the sulfur atom in the olefin sulfoxide, and intramolecular substitution, ring closure and Ramberg-B Bäcklund reaction occurred to remove SO and generate gem-dichloro terminal olefin (Figure 23)
[69].
Later, Zwanenburg et al. Studied in detail the reaction of alkyllithium reagents with dithiocarboxylate olefin sulfoxides 30, using electrophilic reagents to capture the resulting intermediate to obtain the protected carbonyl compound precursor 31, and further deprotection to obtain the corresponding carbonyl compound 32 (Scheme 24)
[70].
Different from the reaction results of aryl ene sulfoxides, Ohno et al. Used the reaction of di-tert-butyl ene sulfoxide with methyl lithium or ethyl lithium reagents to produce thiirane compounds rather than the corresponding sulfoxide compounds, and considered that alkyl lithium reagents nucleophilically attacked the sulfur atom of ene sulfoxides.At the same time, the electron is transferred to the oxygen atom to obtain the oxygen anion instead of the carbanion, because the presence of the aryl group can stabilize the generated carbanion through the conjugation effect, while the alkyl olefin sulfoxide has no such stabilizing effect, so it tends to generate a more stable oxygen anion
[71].
In order to further broaden the diversity of carbanion functional groups, Zwanenburg et al. Have tried the reaction of different kinds of alkali metal organic reagents with olefin sulfoxides, but this kind of reaction can only occur in the presence of excess alkali (Figure 25)
[72].
For the anionic addition product of the first step, the pKa value of the conjugate acid is similar to that of the nucleophile, so the addition reaction is in equilibrium, and the addition of excess base to the system can shift the equilibrium to the right, forming a dianion. This process occurs because of the very strong acidity of the methylene group in the anion formed in the first step.
It is worth noting that when the metal ion species of the nucleophile is changed from sodium and potassium to lithium, completely different reactions occur, resulting in alkenyl sulfones and olefins, respectively (Scheme 26)
[72].
Zwanenburg's group has also studied the reaction of phosphonyl-substituted olefinic sulfoxides 33 with organolithium nucleophiles. In the first step, alkyllithium reagents attack the sulfur atom in olefinic sulfoxides 33, resulting in nucleophilic addition. After hydrolysis, α-phosphonyl sulfoxide compounds 34 are formed, which then react with aldehydes under Wittig-Horner olefination conditions to form α, β-unsaturated sulfoxide compounds 35
[73]. This two-step reaction can also be combined into one step to directly achieve the conversion of α-phosphonoalkene sulfoxides to α, β-unsaturated sulfoxide compounds (Scheme 27).
Different from the work of Ohno et al., which used the reaction of di-tert-butyl olefin sulfoxide with organolithium reagents to produce thiiranes, Metzner's group studied the reaction of organolithium reagents with aliphatic methylthio olefin sulfoxide 36.In this process, the attack of organolithium reagent on the sulfur atom of alkene sulfoxide occurs first, and then the generated carbanion is captured by the electrophile to obtain α-methylthio sulfoxide compound 37, which can be treated with HBF
4/THF/H
2O to obtain new carbonyl compound 38 (Scheme 28)
[71][74]. A year later, Metzner et al. Published a similar thiophilic addition reaction of trithiocarbonate vinyl sulfoxide with organolithium reagents
[35].
3.2.1.2 Reaction of alkaline earth organometallic reagents as thiophiles
Ohno et al. First attempted the reaction of Grignard reagents with bis-aliphatic substituted olefin sulfoxides. According to the steric hindrance difference of the substituents of Grignard reagents, the reaction can undergo different reaction processes: (1) the reaction of primary alkyl Grignard reagent with di-tert-butyl sulfoxide,The carbanion in the Grignard reagent first attacks the sulfur atom in the olefin sulfoxide, and then another molecule of Grignard reagent pulls out the hydrogen in the methylene group and undergoes an intramolecular addition reaction to obtain the thiirane compound; (2) The reaction of secondary alkyl Grignard reagent with di-tert-butyl sulfoxide, the first step also involves nucleophilic attack on the sulfur atom, but the second step is a single electron transfer with another molecular Grignard reagent, and the final protonation produces a sulfide; (3) For the tertiary alkyl-substituted Grignard reagent, the first step does not attack the sulfur atom due to steric hindrance, but directly deoxygenates the thione compound after single electron transfer. The course of the reaction shows that the reaction is intermediate between a single electron transfer and a nucleophilic addition reaction (Scheme 29)
[71].
3.2.1.3 Reaction of organosilicon reagent as thiophilic reagent
In addition to the nucleophilic reactions of alkali-metal and alkaline-earth metal organic reagents on olefin sulfoxides, there are also reported reactions involving organosilicon reagents. This work is mainly from the research group of Leriverend and Metzner, who used fluoride ions to induce the regiospecific nucleophilic attack of organosilicon reagents on the sulfur atom of alkene sulfoxides, and after treatment, allyl and benzyl sulfoxides were obtained (Figure 30)
[75].
3.2.1.4 Reaction of heteroatom as thiophilic reagent
In addition to the reactions involving carbanions as nucleophiles, there are also some thiophilic reactions involving heteroatoms.
When Phillips et al. Studied the reaction properties of the newly synthesized carbamoyl-substituted olefin sulfoxide 39, the olefin sulfoxide was treated with an aqueous solution of strong base KOH to obtain α-chloroamide compound 40, which was considered to be the nucleophilic addition of hydroxyl to the sulfur atom site of the olefin sulfoxide to obtain sulfinic acid and quickly remove the SO
2 to generate α-chloroamide (Figure 31)
[76].
When Zwanenburg et al studied the reductive substitution reaction of p-tolylsulfinate and chloroolefin sulfoxide, they found that at the beginning, a molecule of p-tolylsulfinate attacked the carbon atom site of chloroolefin sulfoxide 41, and a new substitution product p-toluenesulfonyl olefin sulfoxide 42 was formed by addition elimination
[77]. Nucleophilic addition of another molecule of p-tolylsulfinate to the newly formed alkene sulfoxide sulfur atom site, followed by hydrolysis, gave sulfone 43 (Scheme 32).
In addition, alkene sulfoxides with a leaving group at the alpha position of the alkene sulfoxide can also undergo nucleophilic reactions with heteroatom nucleophiles or organometallic reagents at the sulfur atom site of the alkene sulfoxide
[78]. For this type of ene sulfoxide, the presence of the α-geminal dimethyl group can inhibit the competitive dehydrogenation reaction of the basic nucleophile (Scheme 33).
3.2.2 Nucleophilic reaction occurring at the carbon atom of alkene sulfoxide
Compared with the reactions occurring at the sulfur atom, there are relatively few reports on the nucleophilic reactions occurring at the carbon atom of alkene sulfoxides, mainly including the reactions of alkene sulfoxides with easily leaving groups on the carbon atom or the reactions involving special nucleophiles.
Zwanenburg et al. Found that thiophenol and potassium thiocyanate could replace the chlorine in chloroolefin sulfoxide to obtain thiophenyl or thiocyanate substituted olefin sulfoxide, respectively, and the substitution occurred regiospecifically on the carbon atom of chloroolefin sulfoxide (Scheme 34)
[79].
The reaction mainly produces configuration-preserving products, and the reason for the formation of a small amount of configuration-inverting products may be that at the beginning of the reaction, the nucleophile first attacks the plane of the double bond vertically, and at the same time, the chloride ion leaves in the same way. In the anionic intermediate, the energy barrier to rotate the chloride ion to the departure position is not large, which can drive the reaction from one path to another, so a small amount of configuration conversion products will be produced (Scheme 35).
Soon, Zwanenburg et al. Used the reaction of chloroolefin sulfoxide with sodium p-toluenesulfonate to realize the attack of sulfur anion on the carbon atom in olefin sulfoxide, and after the removal of chlorine anion, the reductive substitution reaction of olefin sulfoxide could be realized
[77]. Holm et al. Can also use azide anion to replace chlorine in chloroalkenyl sulfoxide to obtain azidoalkenyl sulfoxide, but the product will quickly decompose into benzonitrile, nitrogen, sulfur and sulfur dioxide at -40 ℃
[80]. Similarly, for this kind of ene sulfoxide with leaving group, such as dichloroene sulfoxide, Jochims et al. Used ammonium thiocyanate as a nucleophile to realize the nucleophilic substitution reaction at the carbon atom site of dichloroene sulfoxide
[81].
Zwanenburg et al. Studied the addition reaction of cyclohexanone enol anion lithium salt 44 to arylthio-substituted ene sulfoxide 45, which is different from the addition reaction of aliphatic lithium reagent to the thiophilic site of ene sulfoxide mentioned above. From the structure of the product, it was inferred that the process occurred at the carbon atom in the ene sulfoxide
[82]. Analogous to the chlorine as a leaving group in chloroalkene sulfoxides, the thiophenyl group can act as a leaving group in thiophenyl-substituted alkene sulfoxides to promote the reaction to achieve nucleophilic substitution at the carbon site. The generated thiophenol anion can be used as a base to react with the product to obtain thiophenol and unsaturated lithium sulfenate, and the thiophenol and the unsaturated lithium sulfenate react with methyl iodide to obtain methyl sulfoxide; And react with thiophenol to give that alkenyl persulfide (scheme 36).
Metzner et al. Found that for simple aliphatic substituted olefin sulfoxides, thioamides can be obtained by using secondary amines as nucleophiles, and imines can be obtained by using primary amines as nucleophiles
[83]. According to the analysis of the experimental results, amines as nucleophiles attack the olefin sulfoxide, first by attacking the carbon atom in the olefin sulfoxide, and then by rearrangement to remove the sulfinic acid to obtain thioamides and imines (Figure 37).
3.3 Reaction of olefin sulfoxide with electrophilic reagent
Since the oxygen atom in the olefin sulfoxide has a certain nucleophilicity, the olefin sulfoxide can act as a nucleophile to react with some electrophiles.
Aminoalkene sulfoxides 46 can be reacted with Meerwein reagent to give imine sulfenates 47 (Scheme 38), which are difficult to prepare by other methods
[84].
3.4 Cycloaddition of olefin sulfoxides
Olefin sulfoxides, as a class of heteroaccumulative diene compounds, can undergo a series of cycloaddition reactions, such as Diels-Alder cycloaddition and 1,3-dipolar cycloaddition. In the Diels-Alder cycloaddition reaction, olefin sulfoxide compounds are relatively active, and 1,3-diene is often used as a trapping agent to verify the formation of olefin sulfoxide. In addition, the configuration of the olefin sulfoxide and the stereoselectivity of the reaction were deduced by analyzing the configuration of the cycloaddition product.
3.4.1 Diels-Alder Cycloaddition of Olefin Sulfoxide
In 1967, Zwanenburg et al. Found that Diels-Alder reaction could occur between olefin sulfoxide and tetrachloro-o-quinone, and o-quinone was used as a diene. The structure of the final product was determined by elemental analysis and infrared spectrum analysis. In the infrared spectrum, the carbonyl absorption peak disappeared, and the S = O absorption peak appeared at the 1150 cm
-1 (Figure 39)
[85].
In 1972, Zwanenburg's group studied the [4 + 2] cycloaddition reaction of ene sulfoxide as a dienophile and 1,3-diene as a diene
[86]. The corresponding [4 + 2] Diels-Alder cycloaddition products (Scheme 40) were obtained in 75% and 56% yields, respectively, by the reaction of fluorenyl sulfoxide with 2,3-dimethylbuta-1,3-diene and by the reaction of fluorenyl sulfoxide with 2,3-dimethylbutane-1,3-diene and buta-1,3-diene.
When fluorenyl sulfoxide was reacted with cyclopentadiene, the cycloaddition product was obtained with an exo: endo ratio of 4:1, but the reason for this stereoselectivity was not explained. When xanthenethione-S-oxide was used to react with 2,3-dimethylbuta-1,3-diene, only 17% of the product was obtained even if the reaction time was prolonged.
Dichloroene sulfoxides are used as dienophiles, which can undergo cycloaddition reactions with dienes more easily than diaryl ene sulfoxides due to their reduced LUMO energy. The stereochemical study of the cycloaddition reaction showed that the reaction of unsymmetrical phenyl chlorovinyl sulfoxide with 2,3-dimethylbuta-1,3-diene could give the product with Z/E configuration, and the difference in configuration of the starting materials was well reflected in the product. Kinetic studies showed that the reaction was found to be a concerted cycloaddition process (Scheme 41).
Zwanenburg et al. Used optically active ene sulfoxides 48 and 49 to react with 1,3-dienes, and the results showed that only a single stereoisomer of the product was produced, proving that chiral ene sulfoxides can achieve asymmetric induction in Diels-Alder reactions (Fig. 4)
[87].
In addition, Zwanenburg et al. Reacted the olefin sulfoxide prepared by the modified Peterson reaction with 2,3-dimethylbuta-1,3-diene to obtain the [4 + 2] Diels-Alder cycloaddition products indenspiro dihydrothiopyran S-oxide and dihydrothiopyran S-oxide
[88][89]. Alkenyl sulfoxides prepared from active methylene containing dihydrothiophenone compounds or active methylene containing compounds protected by silyl enol ether and SOCl
2 can also react with 2,3-dimethylbuta-1,3-diene to obtain dihydrothiopyran S-oxides
[42][90]. It is worth noting that Zwanenburg et al. Found that 3-oxo-2,3-dihydrobenzo [B] thiophene was prepared as an α-oxo olefin sulfoxide starting material with the carbonyl group on the same side as the carbon-sulfur double bond in the olefin sulfoxide by the above method.The ene sulfoxide can be used as an electron-deficient diene, and can undergo a reverse electron demand Diels-Alder cycloaddition reaction with an electron-rich dienophile vinyl ethyl ether to obtain a thiophanone compound (Scheme 42)
[42].
They also used the same method to prepare α-oxo olefin sulfoxide 50 with the carbonyl group on the opposite side of the carbon-sulfur double bond in the olefin sulfoxide, and used it to react with 2,3-dimethylbuta-1,3-diene. The results showed that the reaction used olefin sulfoxide as the dienophile.3-Dimethylbuta-1,3-diene as a diene undergoes a Diels-Alder cycloaddition reaction with normal electron demand, resulting in dihydrothiopyran S-oxide 51, which can be treated in multiple steps to give thiophene compound 52 (Scheme 43)
[91].
Nearly 30 years later, Bergman et al. Used indole series compounds containing active methylene groups to react with SOCl
2 and convert them into α-oxo ene sulfoxides with carbonyl groups on the same side as the carbon-sulfur double bonds in the ene sulfoxides, which were also reacted with 2,3-dimethylbutane-1,3-diene reaction and [4 + 2] cycloaddition to give six-membered ring products, but unfortunately, it has not been verified whether this kind of α-oxoalkene sulfoxide can undergo Diels-Alder reaction with electron-rich alkenes with reverse electron demand
[45].
On the basis of the two chiral ene sulfoxides designed before, Zwanenburg et al. Designed an ene sulfoxide 53 derived from proline by using the modified Peterson reaction again, and studied its asymmetric induction in the Diels-Alder cycloaddition reaction with 2,3-dimethylbuta-1,3-diene
[87][92]. The DE value of the product dihydrothiopyran S-oxide was determined by nuclear magnetic resonance spectroscopy and high performance liquid chromatography (HPLC), and the results showed that the induction effect of this chiral ene sulfoxide was not obvious, which may be due to the fact that the chiral center was too far away from the reaction center, and it was inferred that if the chiral center was closer to the ene sulfoxide group, the induction effect might be better (Figure 5).
Later, Block et al. Used fluoride to induce trimethylsilylmethanesulfinyl chloride to generate ene sulfoxide in situ and react with cyclopentadiene to obtain [4 + 2] cycloaddition product 2-thiabicyclo [2.2.1] hept-5-ene endo-2-oxide. The π-stacking effect between the sulfinyl group and the forming carbon-carbon double bond is the reason for the stereospecific generation of endo type products
[93].
Battaglia et al. studied in detail the cycloaddition reaction of monosubstituted olefin sulfoxides with dienes under heating and Lewis acid induction. Through a large number of experiments, it was found that the interconversion between Z/E of the parent olefin sulfoxides during the reaction process resulted in no good stereoselectivity in the reaction of monoaryl-substituted olefin sulfoxide with butadiene and 2,3-dimethylbuta-1,3-diene
[94]. In addition, the Lewis acid in the reaction can coordinate with the oxygen in the olefin sulfoxide, thereby reducing the energy of the LUMO and improving the electrophilic performance of the olefin sulfoxide. In this report, it was found that the presence of protonic acid trifluoroacetic acid could not only accelerate the formation of ene sulfoxide, but also activate the less reactive ene sulfoxide and increase the rate of cycloaddition reaction between ene sulfoxide and diene.
Hanack et al. Designed and synthesized cyano-substituted olefin sulfoxides. Through the analysis of the single crystal structure of the product thiopyran S-oxide, it was deduced that the raw material olefin sulfoxide was E-type configuration
[95].
Capozzi et al. Developed α, α '-dioxoalkene sulfoxides generated in situ by retro-Diels-Alder reaction, and tried to react with various types of alkenes. When these alkene sulfoxides are used as dienes, they can undergo retro-electron-demanding Diels-Alder cycloaddition with electron-rich vinyl alkyl ethers or p-methoxyphenylethylene
[58]. When such olefin sulfoxides react with dienes, they can act as dienophiles to undergo Diels-Alder cycloaddition reactions with normal electron requirements (Scheme 44).
In addition, Capozzi et al. Also studied the difference of Z/E configuration of olefin sulfoxides generated in situ by retro-Diels-Alder method in cycloaddition reaction
[58a]. It was found that the [4 + 2] cycloaddition of Z/E-olefin sulfoxides with different configurations to dihydropyran gave products with single configuration, while the reaction of Z/E-olefin sulfoxides with 2,3-dimethylbuta-1,3-diene gave thiopyran compounds with corresponding configurations (Scheme 45).
After that, they used a similar method to prepare the precursor compound of α, α '-dioxoalkene sulfoxide. Unlike the previous method, the precursor substrate structure contains an electron-rich alkene functional group. Under the reaction conditions of alkene sulfoxide formation, the active intermediate of α, α' -dioxoalkene sulphoxide quickly undergoes an intramolecular [4 + 2] Diels-Alder reaction with reverse electron demand (Figure 46)
[96].
It is worth noting that Capozzi et al. Converted the carbonyl group in the above olefin sulfoxide precursor into an imine group, and used the retro-Diels-Alder reaction to generate a new type of electron-deficient olefin sulfoxide, such as imine olefin sulfoxide 54, in situ.The reaction with electron-rich alkenes was attempted, and it was found that they underwent Diels-Alder cycloaddition with reverse electron demand, and finally an important class of thiazine compounds 55 was obtained (Scheme 47)
[97].
Capozzi et al. Also found that α-oxoalkene sulfoxides generated in situ using β-oxosulfinamide under catalytic pyridine activation can also be used as dienophiles to react with 2,3-dimethylbuta-1,3-diene or as dienes to undergo Diels-Alder cycloaddition with reverse electron demand to give the corresponding cycloaddition products
[47].
A carbonyl group in that alpha-carbonyl olefin sulfoxide can be combine with a carbon-sulfur double bond in the olefin sulfoxide to be used as a diene to participate in a cycloaddition reaction, and another clas of styryl olefin sulfoxides can also be used as a diene to undergo a Diels-Alder cycloaddition reaction. The olefin sulfoxide compound can be obtained by heat decomposition of 3, 4-dihydro-2H-thiopyran or S-oxide thereof, and can also be generated by beta-elimination of chloroform from allyl trichloromethyl olefin sulfoxide, and can be found to be used as a diene to undergo Diels-Alder cycloaddition reaction when reacted with norbornene or trans-1, 2-dibenzoylethylene (scheme 48)
[98][99][98,99][99].
After that, Maguire et al., in order to verify whether there is an intermediate α-oxoalkene sulfoxide after rhodium-catalyzed decomposition of α-diazosulfoxide compounds, used 2,3-dimethylbuta-1,3-diene to capture the intermediate and generate the corresponding Diels-Alder cycloaddition product, thus verifying the formation of the intermediate
[53]. Subsequently, Maguire et al. Tried to change the reaction conditions from rhodium catalysis to microwave-assisted decomposition of diazosulfoxide compounds, and also used 2,3-dimethylbuta-1,3-diene trapping experiments to prove the formation of olefin sulfoxide as a reaction intermediate.By analyzing the configuration of the product, it was found that the kinetically stable (Z) -oxoalkene sulfoxide could be converted to the thermodynamically more stable (E) -oxoalkene sulfoxide in the absence of diene
[54].
In addition, Morita et al., in order to verify the formation of the key intermediate olefin sulfoxide in the preparation of α-carbonyl olefin sulfoxide by the elimination reaction of heteroaryl sulfoxide compounds, used 2,3-dimethylbutane-1,The formation of six-membered ring products can also be found by the capture of 3-diene, which proves the feasibility of this method. The cis-trans selectivity of the formation of olefin sulfoxide ring products was also discussed by NMR spectrum analysis
[39].
El-Sayed's work was to explore the cycloaddition of sulfonyl alkenyl sulfoxides with asymmetric 2-methylbuta-1,3-diene and (E) -penta-1,3-diene, and the results showed that the process had good regioselectivity and stereoselectivity
[100]. After that, Shermolovych's group obtained a new class of polyfluoroalkyl olefin sulfoxides from dihydropolyfluoroalkane sulfinyl chloride by eliminating HCl, and also studied their properties by [4 + 2] cycloaddition reaction with dienes
[101].
Mazzanti et al. Found that azoalkene 56 could react with fluorene sulfoxide 25 to obtain 1,2,3-thiadiazines by [4 + 2] cycloaddition with reverse electron demand, but diaryl olefin sulfoxide could not react with azoalkene (Scheme 49)
[102].
3.4.2 [3 + 2] Cycloaddition of Olefin Sulfoxides
In addition to the [4 + 2] cycloaddition reaction, the [3 + 2] type dipolar cycloaddition reaction can also occur with olefin sulfoxides.
3.4.2.1 [3 + 2] Cycloaddition of Olefin Sulfoxides as Dipolophile
In 1972, Maccagnani and Zwanenburg et al. Reported the reaction of aromatic olefin sulfoxides with diazoalkanes, mainly giving [3 + 2] 1,3,4-thiadiazole 1-oxides, which are active and slowly decompose even when stored below zero
[103]. The structure of the addition product was determined by further analysis of the light-opened product of the cycloaddition product (Scheme 50). Venier and Gibbs focused on the reaction of diaryl ene sulfoxide with diazomethane. For the important intermediate thiadiazoline S-oxide in the reaction, the carbon of diazomethane preferred to attack the sulfur in the ene sulfoxide first, that is, to form 1,3,4-thiadiazoline S-oxide, but there was no rigorous experimental verification
[104].
In the same year, Zwanenburg et al explored the reaction of diaryl diazomethane with dichloroolefin sulfoxide, and found that the reaction did not produce the expected SO
2 reaction, but produced benzothiophene oxide
[105]. The reaction mechanism was proposed as follows: thiadiazoline S-oxide was obtained by 1,3-dipolar cycloaddition of dichloroolefin sulfoxide and diaryldiazomethane, followed by removal of nitrogen to form thiirane S-oxide and further cyclization to obtain benzothiophene oxide (Scheme 51).
Bonini and Maccagnani developed a new method for the preparation of thiirane S-oxygen compounds by the reaction of diene sulfoxides with diazo compounds.The cis-trans configuration of the compound was determined mainly by the relative position of the hydrogen on the ring and the sulfinyl group, and combined with NMR analysis, it was found that the thiirane S-oxygen compound obtained by this method was mainly trans structure
[106].
Wagenaar and Zwanenburg et al., in order to investigate the stereoselectivity of the product 1,3,4-thiadiazoline produced by the reaction of olefin sulfoxide with diazopropane, selected asymmetric olefin sulfoxides with a single E/Z configuration, and finally obtained 1,3,4-thiadiazoline with a single configuration, which shows that the process is not only regiospecific, but also stereospecific
[107]. In addition, the olefin sulfoxide with large steric hindrance was selected to obtain the non-stereospecific thiirane S-oxide, so it was speculated that the formation of 1,3,4-thiadiazoline was a concerted cycloaddition process, and the introduction of large steric hindrance led to the formation of thiirane S-oxide instead of the five-membered ring.
In addition to studying the reactions of diaryl ene sulfoxides and dichloroene sulfoxides with diazoalkanes, Zwanenburg et al. Also extended the substrates of diaryl ene sulfoxidesto arylsulfonyl-substituted ene sulfoxide, which can directly obtain 1,3,4-thiadiazole compounds rather than 1,3,4-thiadiazoline compounds by conventional column chromatography (Scheme 52)
[103,104,107][108]. In addition, Zwanenburg et al. Selected olefin sulfoxide prepared by direct oxidation of thione as a substrate to explore its reaction with diazomethane and 2-diazopropane
[109].
In addition to using diazoalkanes as 1,3-dipoles, Zwanenburg et al. Also explored the reaction of nitrile imines 57 as 1,3-dipoles with diaryl ene sulfoxides
[110]. The results show that the reaction to form 1,3,4-thiadiazoline S-oxide 58 is regiospecific, but not stereospecific, mainly because the stereospecific product formed at the beginning can be isomerized again to reach a new equilibrium (Scheme 53).
Subsequently, Zwanenburg et al. Tried the 1,3-dipole reaction of olefin sulfoxide as a dipolarophile with benzonitrile oxide 59 (generated in situ from α-chlorooxime and base in ether), and the results showed that the reaction was regio- and stereospecific, so the process was considered to be synergistic
[111]. Similarly, benzonitrile-4-nitrophenyl ylide 60 can also react as a 1,3-dipole with diaryl ene sulfoxides and regiospecifically give 1,3-thiazoline compound 61 (Scheme 54)
[112].
Since then, Franck-Neumann et al. Have studied 3-sulfinyl-1,2-diazole as an ene sulfoxide precursor, which removes nitrogen under illumination, followed by heteroatom-Wolff rearrangement to obtain an ene sulfoxide intermediate, which is then captured by 2-diazopropane to obtain 1,3,4-thiadiazoline S-oxide
[50]. Zwanenburg et al. Also tried the reaction of their developed sterically hindered alkoxy or aryloxy-substituted ene sulfoxides with 2-diazopropane, which also gave 1,3,4-thiadiazoline S-oxides, but unfortunately in low yield due to steric hindrance
[113].
Thiocarbonyl ylides as excellent 1,3-dipoles can likewise undergo dipolar cycloaddition with ene sulfoxides. Mloston and Heimgartner et al. Used 2,5-dihydro-1,3,4-thiadiazole 62 as a thiocarbonylthio ylide precursor to react with diphenyl ene sulfoxide or fluorene ene sulfoxide to obtain the corresponding 1,3-dipolar cycloaddition product 1,3-dithiolane-S-oxide (Scheme 55)
[114].
In the dipolar cycloaddition reactions mentioned above, the olefin sulfoxide is used as a dipolarophile to react with other 1,3-dipoles. However, there are relatively few reports on the dipolar cycloaddition of olefin sulfoxides as 1,3-dipoles.
3.4.2.2 [3 + 2] Cycloaddition of Olefin Sulfoxides as Dipoles
Huisgen et al. Used thione as a dipolarophile to undergo [2 + 3] dipolar cycloaddition reaction with ene sulfoxide, and selected 2,2,4,4-tetramethyl-3-thiocyclobutanone S-oxide 63 as an ene sulfoxide substrate to react with thiobenzophenone to obtain 1,2,4-oxodithiolane 64
[115]. The corresponding cycloaddition compound 65 (Scheme 56) was also obtained by the reaction of fluorenethione.
Machiguchi et al. Realized the [3 + 2] cycloaddition of cycloheptatrienethione S-oxide 66 with enamine
[116]. According to the single crystal structure and NMR analysis, it was found that the C = S bond and the vicinal carbon atom of the olefin sulfoxide reacted with the C = C bond of the enamine via 1,3-dipolar cycloaddition to give sulfoxide compound 67 (Scheme 57).
In addition, some ene sulfoxides with special structures, such as thioketene S-oxide 68, can also be used as 1,3-dipoles to undergo dipolar cycloaddition with imines to give 3-alkylidene-1,2,4-oxathiazolidine compounds 69 (Scheme 58)
[117].
4 Conclusion and prospect
According to incomplete statistics, since the 1960s, the analysis of the literature on olefin sulfoxides shows that the work on olefin sulfoxides was at its peak in the 1970s and 1990s, and the main contributions came from Zwanenburg, Capozzi, Giuseppe, Block, Eric, etc. (Fig. 6). In recent years, the research on olefin sulfoxides has gradually shown an upward trend. For example, in 2017, domestic researchers Professor Zeng Xiaoqing of Soochow University and Professor Zhao Lili of Nanjing University of Technology focused on the properties of methylidene olefin sulfoxides (thioketene S-oxide H
2C=C=S=O) by using matrix isolation infrared spectroscopy and quantum chemical calculation
[118].
In recent years, the research on the properties and reactions of allene sulfoxides has been paid more attention again. Through the review of this paper, it can be found that the research on this important heteroatomic allene compound, allene sulfoxides, is still relatively limited, and there are still many valuable and meaningful places to be explored.
Through the analysis and comparison of olefin sulfoxides and their structurally similar olefins and sulfoxides, we can find that: (1) For olefins, their π electron cloud is easily activated and electrophilic addition reactions occur, but their high electron cloud density makes it difficult for nucleophilic addition reactions to occur. For olefin sulfoxide compounds, according to the resonance formula (Figure 1), it can be found that the carbon atom and sulfur atom in the olefin sulfoxide can be used as electrophilic sites to be directly attacked by nucleophiles and nucleophilic addition reactions occur. At the same time, the oxygen atom in the olefin sulfoxide can also be used as a nucleophilic site for electrophilic addition. (2) For sulfoxide compounds, double bonds are mainly formed through d-p π bonds, and the existence of lone pair electrons of sulfur atoms makes sulfoxide compounds have optical isomers. For the olefin sulfoxide compounds, although there is a lone pair of electrons on the sulfur atom, there is a cis-trans isomer in the olefin sulfoxide compounds due to the existence of carbon-sulfur double bonds. By designing and synthesizing olefin sulfoxides with specific structures and reacting with dienes, we can directly obtain chiral dihydrothiopyran S-oxides which are difficult to synthesize by conventional methods
[87,92].
From the point of view of the synthesis of olefin sulfoxide raw materials, for raw materials containing sulfur sources (thiocarbonyl compounds, etc.), after successful preparation, olefin sulfoxide can only be obtained by oxidation; For raw materials without sulfur sources, external sulfur sources, usually pungent compounds (SOCl2 and SO2, etc.), are inevitably used. Therefore, it is very important to find a method for the preparation of olefin sulfoxides with economical steps and mild reagents, and it is worth exploring.
From the point of view of olefin sulfoxide reactions, such as cycloaddition reactions involving olefin sulfoxide, only Diels-Alder reactions and 1,3-dipolar cycloaddition reactions are involved at present. For the Diels-Alder reaction, the cycloaddition reaction of olefin sulfoxide as a diene or a dienophile is limited to the reaction with olefins. For the reaction of olefin sulfoxides with unsaturated compounds, the alkene substrates can also be extended to other unsaturated compounds such as aldehydes, ketones, imines, alkynes, arynees, etc. Exploring the feasibility of this kind of reaction, as well as the mechanism and stereochemistry involved in the reaction process, on the one hand, we can have a deeper understanding of the properties and reaction mechanism of allene sulfoxides, on the other hand, we can further improve the theoretical system of this kind of heteroatomic allene compounds (ketene, allene sulfone, etc.).
For the reaction of vinyl sulfoxides with conventional carbenes derived from C
1, the reaction mechanism and structure depend on the type of carbene. When dichlorocarbene reacts with it, the [2 + 1] cycloaddition reaction occurs, while in exchange for the common carbene precursor diazo compound, the [2 + 1] cyclization reaction is achieved through a tandem process of nucleophilic addition and intramolecular substitution
[119]. Therefore, exploring the reasons for the formation of chemoselectivity and trying to react other kinds of C
1 sources (sulfur ylides, iodine ylides, carbene precursor hydrazones, etc.) With olefin sulfoxides will be the future development direction of olefin sulfoxides.
National Natural Science Foundation of China(21372025)
National Natural Science Foundation of China(21772010)
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