Allylic sulfoxides, formation

Sulfoxides (R1—SO—R2), which are tricoordinate sulfur compounds, are chiral when R1 and R2 are different, and a-sulfmyl carbanions derived from optically active sulfoxides are known to retain the chirality. Therefore, these chiral carbanions usually give products which are rich in one diastereomer upon treatment with some prochiral reagents. Thus, optically active sulfoxides have been used as versatile reagents for asymmetric syntheses of many naturally occurring products116, since optically active a-sulfinyl carbanions can cause asymmetric induction in the C—C bond formation due to their close vicinity. In the following four subsections various reactions of a-sulfinyl carbanions are described (A) alkylation and acylation, (B) addition to unsaturated bonds such as C=0, C=N or C= N, (C) nucleophilic addition to a, /5-unsaturated sulfoxides, and (D) reactions of allylic sulfoxides. 

Ohta and coworkers used a bacterium, Corynebacterium equi IFO 3730, rather than a fungus, to oxidize eight alkyl phenyl and p-tolyl sulfides to their respective sulfoxides (119, 120) of configuration R. Virtually all of the sulfur compounds were accounted for as the sum of uncreacted sulfide, sulfoxide and sulfone. The enantiomeric purities of the sulfoxides obtained were quite good and are shown below in parentheses. The formation of the allyl sulfoxides in high optical purity is noteworthy. The authors believe that the sulfoxides were formed by enantioselective oxidation of the sulfides rather than by enantioselective oxidation of racemic sulfoxides, since the yield of sulfoxides was greater than 50% in five of the ten oxidations reported (see also Reference 34). 

Subsequently, Kametani and coworkers observed a similar allylic sulfoxide-sulfenate-sulfoxide rearrangement. These authors reported the exceptionally facile ringopening reaction of condensed cyclobutenes facilitated by arylsulfinyl carbanion substituents. For example, treatment of sulfoxide 68 with butyllithium in tetrahydrofuran at — 30°C for 10 min, followed by normal workup, results in the formation of product 71, which can be explained by the intervention of a double [2,3]-sigmatropic rearrangement of the initial product 69 via 70 (equation 32). A similar double [2,3]-sigmatropic rearrangement of 1,4-pentadienylic sulfoxides has also been reported by Sammes and coworkers. ... 

Deprotonation of allylic aryl sulfoxides leads to allylic carbanions which react with aldehyde electrophiles at the carbon atom a and also y to sulfur . With benzaldehyde at — 10 °C y-alkylation predominates , whereas with aliphatic aldehydes at — 78 °C in the presence of HMPA a-alkylation predominates . When the a-alkylated products, which themselves are allylic sulfoxides, undergo 2,3-sigmatropic rearrangement, the rearranged compounds (i.e., allylic sulfenate esters) can be trapped with thiophiles to produce overall ( )-l,4-dihydroxyalkenes (equation 24). When a-substituted aldehydes are used as electrophiles, formation of syn-diols 27 occurs in 40-67% yields with diastereoselectivities ranging from 2-28 1 (equation 24) . ... 

The Evans rearrangement can be driven to completion by the addition of a thiophile, such as trimethylphosphite (Scheme 26.19) 440 46 M This strategy allows the chemistry of the allyl phenyl sulfoxide, or other sulfur precursor, to be exploited before the allyl alcohol is unmasked.4 3 471 474 The addition of phenylsulfenyl chloride to an alkene, followed by the elimination of hydrogen chloride and subsequent rearrangement, provides a useful synthesis of allyl alcohols.473 475 The [2,3]-Evans sigmatropic rearrangement is concerted and allows for stereochemical transfer.476 477 The reverse reaction, formation of the allyl sulfoxide, results from the treatment of an allyl alcohol using a base followed by arylsulfenyl chloride to produce the allyl sulfoxide.478 479... 

A novel synthesis of a-unsaturated sulfines has been introduced by Bra-verman et al. [99]. Et3N or DABCO treatment of allylic and benzylic tri-chloromethyl sulfoxides triggered the elimination of chloroform and formation of the sulfines. It must be stressed that these sulfines are thermally relatively stable, and this stands in high contrast to the corresponding thio-carbonyl compounds unsaturated thioaldehydes cannot be monitored under the same experimental conditions and have to be used at very low temperature or trapped in situ. The first synthesis of thioacrolein S-oxide was achieved by flash vacuum thermolysis of an anthracene allyl sulfoxide [100], and both isomers in a (Z E) ratio of 78 22 were characterised by NMR spectroscopy at -60 °C. 

In the case of steroidal propargylic alcohols the first rearrangement produced a mixture of allenyl sulfoxides, epimeric at the sulfur atom, which reacted with an added nucleophile to produce substituted allylic sulfoxides. Rearrangement of the sulfoxide resulted in the exclusive formation of a-hydroxy derivatives. This reaction sequence has been applied in a synthesis of hydrocortisone acetate74 (Nu = OCH3) from androstene-3,17-dione and in a transformation of mesantrol75 (Nu = malonate) to a spirolactone. 

Like allyl sulfoxides, allylic selenoxides rearrange via a highly ordered five-membered transition state. The arguments, already presented for the allyl sulfoxide rearrangement (Section 4.11.2.1.2.), apply for the rationalization of the high E selectivity of double-bond formation. Table 7 shows some examples7,8,12-15 for the strong preference for E double bonds (see also reference 2, Table V-2, p 148). Trisubstituted (A)-allyl alcohols are also obtained from allyl selenides with a substituent at C-2 of the allylic moiety (entries 8-10)7,8. 

The synthetically most useful oxygen-sulfur transpositions (equation 16) are the allyl sulfenate-allyl sulfoxide and the propargyl sulfenate-allene sulfoxide rearrangements, the driving force of both being the formation of the strong S=0 bond at the cost of the weak O—S bond (Scheme 12). ... 

Clean conjugate addition of appropriate nucleophiles to allenic sulfoxides has been used to produce allylic sulfoxide systems. Homer has described the formation of functionalized allylic alcohols when adding nucleophiles like amines, alcohols or thiols to allenic sulfoxides in excess. If the addition is performed with equimolar amounts at lower temperature, so that the 2,3-sigmatropic rearrangement is avoided, the intermediate addition products (enamines or enol ethers) can be hydrolyzed to the synthetically valuable 3-keto sulfoxides (Scheme 20). ... 

These results can be explained by the relative rates of the formation of the sulfoxide (step a) and of the corresponding sulfone (step b) in the oxidation reaction of thioethers (reaction 1). It is known that, for dialkyl sulfides, such as Et2S, Pr2S and BU2S, sulfoxide formation proceeds much faster than sulfone formation [1], For the allyl sulfide the selectivity in sulfoxide is lower, because the difference in the rates of the two steps (a) and (b) of the oxidation reaction is less important, due to the conjugation of the lone electron pairs on the sulfur atom with the unsaturated system [1],... 

Anion (63), prepared from an allyl sulfoxide and LDA, reacts with alkyl halides at the a-position to give a-alkylat sulfoxides, which undergo rearrangement upon treatment with a thiophile, resulting in formation of allylic alcohols (Scheme 37). This method can be applied to the synthesis of cyclic allylic alcohols (Scheme 38). The reaction of (63) with aldehydes produces a mixture of regioisomers and thus it is less synthetically useful. 

This transformation presumably proceeds with initial formation of allylic sulfilimine 55, which rearranges via an envelope-like transition state to sulfenamide 56 (cf. Scheme 1-XIII). Interestingly, NMR analysis showed that this [2,3]-sigmatropic rearrangement lies totally on the side of this sulfenamide, unlike the allylic sulfoxide-sulfenate ester system, which lies predominantly to the side of the sulfoxide. Similarly, C-3 epimeric dihydrothiazine imine 58 can be converted by an identical pathway to E-erythrp vicinal diamine 59 in an efficient and totally stereoselective manner [Eq. (28)]. 

One property of the sulfoxide group is its ability to stabilize an adjacent carbanion. The combination of alkylation of the sulfoxide and its subsequent rearrangement leads to the synthesis of substituted allylic alcohols. For example, formation of the sulfenate 330 promotes rearrangement to the allyl sulfoxide 331 (3.211). Alkylation of the sulfoxide 331 gave the new sulfoxide 332 and rearrangement... 

Zard has studied the isomerization/Mislow-Evans rearrangement of vinyl sulfoxides such as 237, arising from enolate addition to alkynyl sulfoxides [Scheme 18.60). Isomerization of 237 to the allylic sulfoxide 238 enabled the [2,3]-sigmatropic rearrangement to a-hydroxy-a-vinyl ketone 239. In this case, diastereoselectivity was low in formation of the carbinol center within a steroid framework. Additions to allenyl sulfoxides provide a similar sequence, leading to 2-propenyl substitution at the tertiary alcohol center (not shown). 

What do we mean by transfer of chirality Reactions in which the stereoselective formation of one stereogenic center is connected to the destruction of another stereogenic center involve transfer of chirality. Sigmatropic rearrangements are a large family of intramolecular reactions that often can be used to transfer chirality. We will look at two examples (1) the Claisen rearrangement (of allyl vinyl ethers to j8,7-unsaturated carbonyl compounds) and (2) the Mislow-Evans rearrangement (of allylic sulfoxides to allylic alcohols via sulfenate esters). 

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