Chiral sulfide

Another example of asymmetric induction in the transfer of chirality from tricoordinate sulfur to the nitrogen atom was reported by Kobayashi (157), who found that methylation of benzylethylani-line with (+)-methoxymethyl-p-tolylsulfonium salt 113 yields (-)-benzylethylmethylphenylammoniumtetrafluoroborate 268. A similar asymmetric methylation reaction was observed with benzyl ethyl sulfide. Chiral ammonium 268 and sulfonium salts 112 were formed... 

Allenmark SG, Andersson MA (1998) Chloroperoxidase-Induced Asymmetric Sulfoxidation of Some Conformationally Restricted Sulfides. Chirality 10 246... 

Catalytic Nitrene Transfer to Heteroatoms. The experimental procedure described above for the copper-catalyzed aziridination of olefins can be applied to the imidation of sulfides, where CuOTf in conjunction with PhI=NTs mediates the formation of siilfimides in good yields (eq 95). Spontaneous [2,3] sigma-tropic rearrangements occur in the case of allylic sulfides. Chiral bis(oxazoline)-CuOTf complexes catalyze both reactions with acceptable enantioselectivities (eq 96). Chloratnine-T is also a suitable but less efficient nitrene precursor. Selenides undergo the same catalytic asymmetric imidation to afford selenimides albeit with lower yields and enantioselectivities. ... 

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

Chiral chemical reagents can react with prochiral centers in achiral substances to give partially or completely enantiomerically pure product. An example of such processes is the preparation of enantiomerically enriched sulfoxides from achiral sulfides with the use of chiral oxidant. The reagent must preferential react with one of the two prochiral faces of the sulfide, that is, the enantiotopic electron pairs. 

An achiral reagent cannot distinguish between these two faces. In a complex with a chiral reagent, however, the two (phantom ligand) electron pairs are in different (enantiotopic) environments. The two complexes are therefore diastereomeric and are formed and react at different rates. Two reaction systems that have been used successfully for enantioselective formation of sulfoxides are illustrated below. In the first example, the Ti(0-i-Pr)4-f-BuOOH-diethyl tartrate reagent is chiral by virtue of the presence of the chiral tartrate ester in the reactive complex. With simple aryl methyl sulfides, up to 90% enantiomeric purity of the product is obtained. 

A second method uses sodium periodate (NaI04) as the oxidant in the presence of the readily available protein bovine serum albumin. In this procedure, the sulfide is complexed in the chiral envirorunent of the protein. Although the oxidant is achiral, it encounters the sulfide in a chiral envirorunent in which the two faces of the sulfide are differentiated. 

Since cbiral sulfur ylides racemize rapidly, they are generally prepared in situ from chiral sulfides and halides. The first example of asymmetric epoxidation was reported in 1989, using camphor-derived chiral sulfonium ylides with moderate yields and ee (< 41%) Since then, much effort has been made in tbe asymmetric epoxidation using sucb a strategy without a significant breakthrough. In one example, the reaction between benzaldehyde and benzyl bromide in the presence of one equivalent of camphor-derived sulfide 47 furnished epoxide 48 in high diastereoselectivity (trans cis = 96 4) with moderate enantioselectivity in the case of the trans isomer (56% ee). ... 

Reagent-controlled aziridination using camphor-derived chiral sulfide 47 has been reported with ee values of 84-98% for the trans isomer although the tram cis ratio was... 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

The inverse electron-demand Diels-Alder reaction is also accelerated by Lewis acids, but the successful application of chiral Lewis acids to this kind of Diels-Alder reaction is very rare. Marko and coworkers applied Kobayashi s catalyst system (Yb(OTf)3-BINOL-amine) to the Diels-Alder reaction of 3-methoxycarbonyl-2-py-rone with vinyl ether or sulfide [58] (Scheme 1.72, Table 1.29). A bulky ether or... 

Solladie-Cavallo s group used Eliel s oxathiane 1 (derived from pulegone) in asymmetric epoxidation (Scheme 1.3) [1]. This sulfide was initially benzylated to form a single diastereomer of the sulfonium salt 2. Epoxidation was then carried out at low temperature with the aid of sodium hydride to furnish diaryl epoxides 3 with high enantioselectivities, and with recovery of the chiral sulfide 1. 

The Aggarwal group has used chiral sulfide 7, derived from camphorsulfonyl chloride, in asymmetric epoxidation [4]. Firstly, they prefonned the salt 8 from either the bromide or the alcohol, and then formed the ylide in the presence of a range of carbonyl compounds. This process proved effective for the synthesis of aryl-aryl, aryl-heteroaryl, aryl-alkyl, and aryl-vinyl epoxides (Table 1.2, Entries 1-5). 

Table 1.1 Synthesis of aryl-vinyl epoxides by use of chiral sulfide 1 a phosphazene base.

Table 1.2 Application of the chiral sulfide 7 in asymmetric epoxidations.

Metzner et al. also prepared the selenium analogue 17 of their C2 symmetric chiral sulfide and tested it in epoxidation reactions (Scheme 1.6) [8]. Although good enantioselectivities were observed, and a catalytic reaction was possible without the use of iodide salts, the low diastereoselectivities obtained prevent it from being synthetically useful. 

Saito has recently reported high yields and enantioselectivities in aziridine synthesis through reactions between aryl- or vinyl-substituted N-sulfonyl imines and aryl bromides in the presence of base and mediated by a chiral sulfide 122 (Scheme 1.41) [66]. Aryl substituents with electron-withdrawing and -donating groups gave modest transxis selectivities (around 3 1) with high enantioselectiv-... 

When ot, 3-unsaturated aldehydes were employed, vinylepoxides were obtained with excellent transxis ratios but in poor yields. When benzaldehyde was treated with a, 3-unsaturated tosylhydrazone salts, the yields of vinylepoxides were improved but the transxis ratios dropped. When chiral sulfides were utilized, the ees were high with a, 3-unsaturated aldehydes, whereas unsaturated, chiral sulfur ylides gave moderate ees, poor yields, and modest transxis ratios. 

An alternative process for the synthesis of vinylepoxides was clearly needed, so reactions with stoichiometric amounts of chiral sulfide were investigated (Scheme 9.16a) [74]. Indeed, when benzyl sulfonium salt 20 was treated with unsaturated aldehydes, the ees and des were high in all cases, whereas the yields [75] were highly substrate-dependent. The same products could be formed by treatment of an unsaturated sulfonium salt with benzaldehyde, but the yields and se-lectivities were generally slightly lower. 

Scheme 9.16 Stoichiometric epoxidation with chiral sulfides.

Metzner and co-workers reported a one-pot epoxidation reaction in which a chiral sulfide, an allyl halide, and an aromatic aldehyde were allowed to react to give a trons-vinylepoxide (Scheme 9.16c) [77]. This is an efficient approach, as the sulfonium salt is formed in situ and deprotonated to afford the corresponding ylide, and then reacts with the aldehyde. The sulfide was still required in stoichiometric amounts, however, as the catalytic process was too slow for synthetic purposes. The yields were good and the transxis ratios were high when Ri H, but the enantioselectivities were lower than with the sulfur ylides discussed above. 

The a-lithiated sulfides 33 are another class of chiral organometallic reagent, readily available by deprotonation of the parent l-(phcnylthio)alkanes 32 with butyllithium in tetrahydrofuran at - 78 °C. 

The best conditions for the a-regioselective coupling of a chiral, highly substituted, lithiated allyl sulfide to a chiral aldehyde were carefully worked out for the key step in an erythronolide B total synthesis108. 

The big difference between the extent of asymmetric induction on the addition to a prostereogenic carbonyl group of simple carbanions a to a chiral sulfoxide on the one hand and enolates of sulfinyl esters on the other, can be attributed to the capacity of the ester function to chelate magnesium in the transition states and intermediates. The results already described for the addition of chiral thioacetal monosulfoxide to aldehydes (see Section 1.3.6.5.) underscore the importance of other functions, e.g., sulfide, for the extent of asymmetric induction. 

Borane, 1-methylbenzylaminocyanohydropyrrolyl-, 3, 84 Borane, thiocyanato-halogenohydro-, 3,88 Borane, trialkoxy-amine complexes, 3, 88 Borane, triaryl-guanidine complexes, 2,283 Borane, trifluoro-complexes Lewis acids, 3,87 van der Waals complexes, 3, 84 Borane complexes aminecarboxy-, 3,84 aminehalogeno-, 3, 84 amines, 3, 82, 101 B-N bond polarity, 3, 82 preparation, 3, 83 reactions, 3, 83 bonds B-N, 3, 88 B-O, 3, 88 B-S, 3, 88 Jt bonds, 3, 82 carbon monoxide, 3, 84 chiral boron, 3, 84 dimethyl sulfide, 3, 84 enthalpy of dissociation, 3, 82... 

The earliest attempts to obtain optically active sulfoxides by the oxidation of sulfides using oxidants such as chiral peracids did not fare well. The enantiomeric purities obtained were very low. Biological oxidants offered great improvement in a few cases, but not in others. Lately, some very encouraging progress has been made using chiral oxaziridines and peroxometal complexes as oxidants. Newer developments in the use of both chemical oxidants and biological oxidants are described below. 

Imamoto and Koto131 prepared some interesting chiral oxidants (104) by the reaction of iodosyl benzene with tartaric anhydride. Methyl p-tolyl sulfide (105) was oxidized by 104c to the sulfoxide in 80% yield with 40% e.e. Methyl p-tolyl, o-tolyl and o-anisyl sulfides (105-107) were oxidized by 104a to their sulfoxides with the enantiomeric purities shown. 

Several alkyl aryl sulfides were electrochemically oxidized into the corresponding chiral sulfoxides using poly(amino acid)-coated electrodes448. Although the levels of enan-tioselection were quite variable, the best result involved t-butyl phenyl sulfoxide which was formed in 93% e.e. on a platinum electrode doubly coated with polypyrrole and poly(L-valine). Cyclodextrin-mediated m-chloroperbenzoic acid oxidation of sulfides proceeds with modest enantioselectivity44b. 

Modena and colleagues47 have developed use of some chiral, non-racemic terpene alcohols as directing groups for highly diastereoselective m-chloroperbenzoic oxidation of sulfides into sulfoxides. Specifically the isobornyl vinylic sulfides 8 undergo hydroxyl-directed oxidation to give a 9 1 ratio of diastereomeric sulfoxides (equation 11). 

---