Regioselective homoallyl alcohols

Regioselective Hydrogenation- allylic and homoallylic alcohols are hydrogenated faster than isolated double bonds... 

Allyllic ether 53 is oxidized regioselectively to the /3-alkoxy ketone 54, which is converted into the a,/i-unsaturated ketone 55 and used for annulation[99]. The ester of homoallylic alcohol 56 is oxidized mainlv to the 7-acetoxy ketone 57[99]. 

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. 

Several strategies have been proposed to improve the regioselectivity of nitrile oxide cycloaddition. Kanemasa and coworkers have reported high-rate acceleration and regioselectivity in nitrile oxide cycloadditions to the magnesium alkoxides of allylic and homoallylic alcohols (Eq. 8.64)."... 

Scheme 11). This kind of catalyst is regioselective, the remote C=C being unaffected, thus indicating that the allylic alcohol group provides a necessary secondary coordination during the cycle. Further confirmation comes from the evidence that extension of the carbon chain by just one more carbon, with respect to homoallylic alcohols, results in no reaction. 

Durandetti et al. have described iron-catalyzed electrochemical allylation of carbonyl compounds with allylic acetates (Equation (27)).333 In the case of aldehydes, slow addition of the corresponding aldehyde is required in order to avoid pinacol formation. With crotyl acetate (R3 = Me), the reaction proved to be highly regioselective, providing almost exclusively branched homoallylic alcohols 150. 

As demonstrated in recent work by Obora and Ishii, alkynes serve as allyl donors in carbonyl allylations from the alcohol oxidation level [277]. Specifically, upon exposure to an iridium catalyst generated in situ from [lr(OH)(cod)]2 and P( -Oct)3, l-aryl-2-methylalkynes couple to primary alcohols to furnish homoallylic alcohols with complete branched regioselectivity and excellent levels of diastereoselectivity (Scheme 17). 

Silyl homoallylic alcohols are obtained with high y-regioselection and E-stereoselection on reaction of chiral alkoxy- and aminomethyl-substituted a -silylallyl carbanions with aldehydes factors which influence the diastereomeric excess have been identified. 

Reaction of the bis (allyl) titanium complexes -16 with saturated and unsaturated aldehydes at -78 °C in the presence of 1.1 equiv of ClTi(OiPr)3 afforded the corresponding Z-anti-configured homoallyl alcohols 4 with >98% regioselectivity and >98% diastereoselectivity in good yields (Scheme 1.3.6) [14]. 

Failure for Grignard reagents to undergo similar additions to homoallylic amines may be explained by the greater stability of the complexes between an amine and zinc rather than magnesium. By contrast, addition of allylzinc bromide to allyl or homoallyl alcohols proceeded considerably less efficiently compared to amines and the regioselectivity was reversed (equation 55)81. 

Reaction of cinnamyl alcohol (36) catalyzed by Rh-BINAPHOS gives the product as lactol 37 (1 1 mixture of diastereomers at the anomeric carbon) with high enantioselectivity (88% ee) [94] (Scheme 7.7). The enantiopurity of lactol 37 is determined by oxidizing the lactol to the corresponding lactone 38. In the same manner, homoallyl alcohol (39) is converted to the corresponding a-methyl-y-butyrolactone (42) with 73% ee via lactol 40 [94] (Scheme 7.7). However, the regioselectivity of the reaction is not favorable to the formation of 40, forming achiral 6-lactol 41 as the major product. 

W. Adam, C. R. Saha-Moller, and K. S. Schmid, Synthesis of 4,6-dideoxyfuranoses through the regioselective and diastereoselective oxyfunctionalization of a dimethylphenylsilyl-substituted chiral homoallylic alcohol, J. Org. Chem., 66 (2001) 7365-7371. 

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. 

Halohydrins. In the presence of 1 equiv. of Ti(0-i-Pr)4, bromine or iodine converts epoxides of rra/ts-allylic or homoallylic alcohols to halohydrins at 0-25° in high yield with marked regioselectivity. The presence of the free hydroxyl group is essential for regioselectivity. 

In 1990, Griesbeck and Stadtmiiller [46] found that the reaction of benzalde-hyde with homoallylic alcohols did not show diastereoselectivity. Ten years later Adam and co-workers showed that allylic alcohols reacted with benzophenone to give the corresponding adducts with high regioselectivity and diastereoselectivity (Scheme 3.40) [78-80]. 

Such remarkable regioselectivities are not obtainable with any other reagent. Metal catalyst-hydroperoxide systems also exhibit extremely high stereoselectivities. For example, in contrast to its reaction with peracids, the homoallylic alcohol (XIV) afforded only the syn-epoxy alcohol with f-Bu02 H-Mo(CO)6 466 ... 

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