Faunce, JA; Grisso, BA; Mackenzie, PB
Optically active, mono- and disubstituted trimethylsilyl 2-[(E)-1-alkenyloxy]ethanoates of the type RR1CH = CHOCHR2CO2SiMe3 (R = Me, PhCH2, n-Bu, MeO2CCMe2CH2, PhSCH2; R1 = H, Me; R2 = Me, c-C6H11) undergo highly diastereoselective, Lewis acid catalyzed reactions with aliphatic and aromatic acetals R3CH(OR4)2 (R3 = H, Me, t-Bu, Ph; R4 = Me, CH2Ph) to afford cis-2-[RR1CH(R3CHOR4)]-5-R2-1,3-dioxolanones corresponding to erythro-diastereoselective aldol reactions involving net syn-periplanar addition of the acetal-derived electrophile and trimethylsilyl ester oxygen across the enol ether double bond. Analysis of the alcohols RR1C(R3CHOR4)CH2OH obtained by reductive removal of the ethanoate auxiliary reveals the following points. (1) Enantiomeric excesses in the range 90-98% ee are possible with dimethyl and dibenzyl acetals derived from formaldehyde, acetaldehyde, pivalaldehyde, and benzaldehyde. (2) The aldol reactions are moderately to highly erythro diastereoselective (e/t = 4:1-99:1), even when quaternary and tertiary centers are juxtaposed (R1 = Me; e/t = 13:1-32:1). (3) The highest diastereoselectivities are observed with a bulky cyclohexyl substituent at the primary chiral center (R2 = Cy); however, diastereoselectivities as high as 88% ee are possible even with lactic acid derivatives (R2 = Me). (4) The enantiomeric excesses are catalyst dependent, with Me3SiOTf giving slightly better results than Ph3CSbCl6 in reactions with benzaldehyde dimethyl acetal but Ph3CSbCl6 giving much better results than Me3SiOTf in reactions with acetaldehyde dimethyl acetal. (5) Perhaps most notably, the diastereoselectivities are remarkably insensitive to changes in substitution at the nucleophilic enol ether carbon, so that essentially identical results are observed regardless of whether R = PhCH2, MeO2CCMe2CH2, or PhSCH2 and regardless of whether R1 = H or Me. Reaction of the symmetrically disubstituted enol ether Me2C = CHOCH(c-C6H11)CO2SiMe3 with PhCH(OMe)2 affords, after reduction with LiALH4, Me2C(PhCHOMe)CH2OH of 94% ee. PhCHO and PhCH2CH = CHOCH(c-C6H11)CO2SiMe3 undergo a similar reaction to afford, after aqueous workup and reduction, threo-PhCH2CH(PhCHOH)CH2OH (e/t = 1:13; 98% ee). The corresponding methyl ester, PhCH2CH = CHOCH(c-C6H11)CO2Me, undergoes related aldol condensation/transacetalization chemistry upon reaction with the same acetals and Me3SiOTf to afford erythro-PhCH2CH(R3CHOR4)CH(OR4)2 products in 61-86% nonoptimized yield, with erythro/threo ratios and enantiomeric excesses identical with those observed for the corresponding trimethylsilyl ester reaction products.