Homoallylic alcohol from epoxide

Another interesting investigation was reported by J.A. Prieto et al. describing the microwave-assisted VO(acac)2-catalyzed epoxidation [179] of hindered homoallylic alcohols. From a synthetic point of view this is of particular interest as the literature abounds with examples of syntheses of 3,4-epoxy alcohols, owing to their potential in the generation of valuable intermedi-... 

An interesting feature of the Corey proposal is that it predicts that homoallylic alcohols should epoxidize from the opposite face compared with allylic alcohols. This arises because the stereoelectronically favorable conformation available for the hydrogen bond of homoallylic alcohols in 7 projects the alkyl chain of the homoallylic alcohol below the plane described by the titanium and the fm-butyl hydroperoxide ring. This is the only conformation that places the tt-bond of the allylic alcohol in a position to receive the peroxy oxygen of the hydroperoxide. In the initial report of enantioselective epoxidation32 it was indeed observed that homoallylic alcohols epoxidized from the opposite face compared to allylic alcohols. 

In contrast to the previous methods involving reductive coupling of two 71-components, a method involving participation of the sigma bond of an epoxide has been demonstrated. Treatment of a monosubstituted epoxide and alkyne with EtaB in the presence of a nickel catalyst generated from Ni(cod)2 and PBus affords homoallylic alcohols from reductive coupling (Scheme 3-67). The process proceeds with retention of epoxide stereochemistry, and intramolecular versions are endoselective. These aspects can be explained by initial oxidative addition of Ni(0) to... 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

Sulfonic peracids (66) have also been applied recently to the preparation of acid sensitive oxiranes and for the epoxidation of allylic and homoallylic alcohols, as well as relatively unreactive a, p - unsaturated ketones. These reagents, prepared in situ from the corresponding sulfonyl imidazolides 65, promote the same sense of diastereoselectivity as the conventional peracids, but often to a higher degree. In particular, the epoxidation of certain A -3-ketosteroids (e.g., 67) with sulfonic peracids 66 resulted in the formation of oxirane products (e.g., 68) in remarkably high diastereomeric excess. This increased selectivity is most likely the result of the considerable steric requirements about the sulfur atom, which enhances non-bonded interactions believed to be operative in the diastereoselection mechanism <96TET2957>. 

The vanadium-catalyzed epoxidation of hindered homoallylic alcohols has been described by Prieto and coworkers [339]. Reaction times for the epoxidation in a series of cis- and trans-2-methyl-alkenols were significantly reduced from 6-10 days to... 

Epoxide ring-opening with transfer of an sp carbon moiety was applied in a short synthesis [44] of eicosanoid 56 [45], relevant in marine prostanoid biosynthesis (Scheme 9.13). Homoallyl alcohol 55 was obtained in good yield from 54 by use of a cyano-Gilman alkenylcuprate [46]. 

Fig. 2 Mechanism for the formation of tetrahydropyran from epoxide and homoallylic alcohol...

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]. 

Stereoselective epoxidation. A detailed study of epoxidation of homoallylic alcohols with this system indicates that the direction and degree of stereoselectivity can be predicted from a vanadate ester transition state with the chair comformation A. for example, the selectivity is > 100 1 when R1 and R4 = H and R3 and R - alkyl, since 1,3-interactions are minimal. R1 can also be a methyl group, but the reaction is slowed. When R1 = isopropyl and R3 = methyl, severe 1,3-interactions in both chair forms result in low asymmetric induction (2 1 selectivity).2... 

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). 

The epoxidation of the homoallylic alcohol (100) is regio- and stereo-selective (equation 36). Epoxi-dation of (100) from the -face involves a transition state which can be approximate by the conformer (102) complexed with MCPBA in this conformation there is steric interference between the tertiary allylic hyctogen and ethyl group. Inspection of conformation (103) reveals that in the transition state leading to the a-epoxide there is steric interaction between the ethyl and allyl groups the steric interaction in (103) is much larger than the interaction in (102). 

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