Alcohols, homoallylic, chiral from epoxides

Chiral alkenyl and cycloalkenyl oxiranes are valuable intermediates in organic synthesis [38]. Their asymmetric synthesis has been accomplished by several methods, including the epoxidation of allyl alcohols in combination with an oxidation and olefination [39a], the epoxidation of dienes [39b,c], the chloroallylation of aldehydes in combination with a 1,2-elimination [39f-h], and the reaction of S-ylides with aldehydes [39i]. Although these methods are efficient for the synthesis of alkenyl oxiranes, they are not well suited for cycloalkenyl oxiranes of the 56 type (Scheme 1.3.21). Therefore we had developed an interest in the asymmetric synthesis of the cycloalkenyl oxiranes 56 from the sulfonimidoyl-substituted homoallyl alcohols 7. It was speculated that the allylic sulfoximine group of 7 could be stereoselectively replaced by a Cl atom with formation of corresponding chlorohydrins 55 which upon base treatment should give the cycloalkenyl oxiranes 56. The feasibility of a Cl substitution of the sulfoximine group had been shown previously in the case of S-alkyl sulfoximines [40]. 

The lithium derivative of the chiral chelating diamine (3 )-2-(l-pyrrolidinylmethyl)-pyrrolidine (6) has been used extensively in stereoselective synthesis, i.e. in the deprotonation of ketones and rearrangement of epoxides to homoallylic alcohols. The lithium amide has been crystallized from toluene solution, and X-ray analysis revealed that it forms a ladder-type tetramer with the two pyrrolidine nitrogens solvating the two lithiums at the end of the ladder38, (Li-6)4. 

Chiral all-syn-l,3-polyols. A reiterative route to these polyols from an optically active epoxide (1) involves ring opening with a cuprate derived from vinyllithium and copper(I) cyanide (11, 366-367) to give an optically active homoallylic alcohol (2). This is converted into the fepoxide (4) via a cyclic iodocarbonate (3) by a known procedure (11, 263). Repetition of the cuprate cleavage results in a homoallylic 1,3-diol (5). The ratio of desired syn- (o anfi-diols is 10-15 1. This two-step sequence can be repeated, with each 1,3-diol unit formed being protected as the acetonide. The strategy is outlined in Scheme (I). 

Diamides of tartaric acid with primary amines have been used as chiral ligands for titanium-and zirconium-catalyzed epoxidations of homoallylic alcohols by the Sharpless method (Section D.4.5.2.4.). Such diamides are conveniently obtained from dimethyl or diethyl tartrate by reaction with the corresponding amine38. The iV,A A, /V -tetrarnethyl diamide has been used for the formation of chiral dioxolanes (Section D.1.5.1.) and in the synthesis of chiral alkenes (Section D.l.6.1.5.). 

Non-racemic epoxide 307, prepared from (+)-epichlorohydrin, was alkeny-lated to give allyl silane 308, which was converted into allyl stannane 309. Corey s chiral boron reagent-mediated asymmetric allylation [120] to aldehyde 311 provided homoallylic alcohol 306 with a 11 1 diastereomer ratio. Intramolecular Sn2 cyclization of the corresponding 7-hydroxy-3-TsO unit derived from 306, followed by hydrolysis of the dithiane, afforded aldehyde 312 (Scheme 66). 

Chiral sulfoxides can also be used in a stereodivergent manner to construct homoallylic alcohols, which are common structure motifs in the total synthesis of natural products - prominent examples are the leucotrienes. They can be synthesized readily from a-sulfinyl epoxides as described in Scheme 3.24 [46]. 

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