Alkenes, homoallylic hydroxylation

The Simmons-Smith reaction " and its variants are widely used for the stereospecific synthesis of cyclopropane compounds. The methodology involves the use of copper-treated zinc metal (the zinc-copper couple) with diiodomethane to add methylene to a carbon-carbon double bond. Alternative use of diazomethane in catalytic reactions does not offer the same synthetic advantages and is usually avoided because of safety considerations. As significant as is the Simmons-Smith reaction for cyclopropane formation, its employment for organic synthesis was markedly advanced by the discovery that allylic and homoallylic hydroxyl groups accelerate and exert stereochemical control over cyclopropanation of alkenes (e.g, Eq. 21), and this acceleration has been explained by a transition state model... 

Employing protocol V with the methanesulfonamide catalyst 122, a 93 7 er can be obtained in the cyclopropanation of cinnamyl alcohol. This high selectivity translates well into a number of allylic alcohols (Table 3.12) [82]. Di- and tri-substi-tuted alkenes perform well under the conditions of protocol V. However, introduction of substituents on the 2 position leads to a considerable decrease in rate and selectivity (Table 3.12, entry 5). The major failing of this method is its inability to perform selective cyclopropanations of other hydroxyl-containing molecules, most notably homoallylic alcohols. 

The hydroxyl group at the allylic position has a significant effect on the syn/anti methyl stereoselectivity [67,68] and the diastereoselectivity [63,64] of the photo-oxygenation ene reaction (see Sec. II.B). To assess the effect of the hydroxyl at the more remote homoallylic position, the reaction of O with the geminal dimethyl trisubstituted homoallylic alcohols (85, 86, 89) and the cis dis-ubstituted 90 was examined in nonpolar solvents [116], The regioselectivity trend was compared with that of the structurally similar trisubstituted alkenes (87, 88, 91) [105], The results are summarized in Table 12. 

For alkenes 87, 88, and 91, the regiochemistry is solely dependent on the steric hindrance of the allylic substituent. It is obvious that the regioselectivity trend for the homoallylic alcohols 85, 86, and 89 is different from that of compounds 87, 88, and 91, respectively, although the hydroxyl group exerts approximately the same steric hindrance as a methyl group. 

Substituents occupying sites more remote from the alkenic center than the allylic position may also influence the direction of attack on an alkene with diastereotopic Tr-faces. Thus, cyclic alkenes with a sul-foximine group attached to an exocyclic homoallylic carbon atom and a hydroxy group at the allylic position, for example (Iti) in equation (5), undergo syn hydroxylation with a very high degree of dia-stereoselectivity, diol (17) being produced as the sole diastereoisomer. ... 

Diastereoselective hydroxylation has also been observed at an alkenic center in an acyclic system that is guided by a sulfoxide group that is more remote than the homoallylic position. Alkenes (18 equation... 

On the basis of this rearrangement, an efficient synthetic route to pyrrolidines such as (46) was developed by Overman, starting from oxazolidine (42), via hydroxylated homoallylic imines such as (43 Scheme 22).Mechanistically, the formation of (46) may explained as a tandem-type combination of a cationic aza-Cope rearrangement with a subsequent Maimich cyclization (route a) or, alternatively, as an alkene-iminium ion cyclization/pinacolic rearrangement sequence (route b). 

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