Chiral vinyl ether alcohols

Claisen rearrangement of allyl vinyl ethers. Thermal rearrangement of vinyl ethers (3) of sec-allylic alcohols in the presence of 1 or 2 leads to the aldehyde 4. Rearrangement of the optically active 5 is accompanied by transfer of chirality, particularly in the case of 1. 

Three different strategies have been envisaged. The chiral information can either be incorporated into the alkyne or linked to the heteroatom or to the a,/ -unsaturated substituent at the carbene complex carbene carbon. High diastereoselectivities (57a 57b >96 4) have been observed in reactions of vinyl carbene complex 55 with the chiral propargylic ether 56 bearing the bulky trityloxy substituent [57a]. A more general approach is based on chiral alcohols incorporated into the alkoxycarbene complex. Upon benzannulation with tert-butylethyne, the menthyloxy carbene complex 58 gave a diastereoselectivity of 10 1 in favor of the naphthalene tricarbonylchromium complex 59a [57c, 57d]. Finally, the tandem benzannulation-Mitsunobu reaction of optically active carbene complex 60 with 5-hexyn-l-ol afforded the anti-benzoxepine complex 61 as the only diastereomer (Scheme 23) [57b]. 

Fig. 11.42. Preparation of an allyl enol ether, D, from allyl alcohol and a large excess of ethyl vinyl ether. Subsequent Claisen rearrangement D —> C proceeding with chirality transfer.

R)-(-)-2,2-Diphenylcyclopentanol (1) is a highly effective chiral auxiliary in asymmetric synthesis. Hydrogenation of chiral 0-acetamidocrotonates derived from this alcohol has afforded the corresponding 0-amido esters with high diastereoselectivity (96% de).6 In addition, (R)-1 has been used as a chiral auxiliary in Mn(lll)-based oxidative free-radical cyclizations to provide diastereomerically enriched cycloalkanones (60% de).7 Our interest in (R)-(-)-2,2-diphenylcyclopentanol is its utility as a chiral auxiliary in Lewis acid-promoted, asymmetric nitroalkene [4+2] cycloadditions. The 2-(acetoxy)vinyl ether derived from alcohol (R)-1 is useful for the asymmetric synthesis of 3-hydroxy-4-substituted pyrrolidines from nitroalkenes (96% ee).8 In a similar fashion, a number of enantiomerically enriched (71-97% ee) N-protected, 3-substituted pyrrolidines have been prepared in two steps from 2-substituted 1-nitroalkenes and (R)-2,2-diphenyl-1-ethenoxycyclopentane (2) (see Table).9... 

In an analogous manner, propargyl vinyl ethers with a pendant alcohol group as internal nucleophile gave 5,6- or 6,6-spiroketals with excellent diastereoselectivity (Scheme 4-49). This transformation is an example for efficient center-to-axis-to-center chirality transfer. 

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