A systematic study of the effects of relative configuration, protecting group, and enolate type on the diastereoselectivities of aldol reactions of a chiral ethyl ketone with 2-methylpropanal.

The diastereoselectivities of aldol reactions of 2-methylpropanal with various enolates of 5-O-methoxymethyl and 5-O-triethylsilyl derivatives of the four racemic diastereomers of 6-(2-ethyl-1,3-dioxolan-2-yl)-5-hydroxy-4-methylheptan-3-one are reported. Reactions of the (E)-enol dicyclohexylborinates, (Z)-enol 9-BBN borinates (i.e., 9-((Z)-enoxy)-9-borabicyclo[3.3.1]nonanes), Li (E)-enolates, Li (Z)-enolates, and Ti(IV) (Z)-enolates were examined. Boron and Li enolates were prepared by standard methods, but Ti(IV) enolates were obtained via transmetalation of the Li (Z)-enolates by reaction with TiCln(Oi-Pr)(4-n) (n = 0-2). Aldol relative topicity (simple diastereoselectivity) was strongly correlated to the enolate geometry: anti aldols from (E)-enolates and syn aldols from (Z)-enolates. However, for each enolate type, the diastereoface selectivities varied widely (by factors of 5-400) with the relative configuration and nature of the C5 protecting group in the 8 starting ketones. Plausible transition state models are postulated to rationalize some of these observations. The relative configurations for the complete set of 16 diastereomeric 2-(2-ethyl-1,3-dioxolan-2-yl)-7-hydroxy-3-(methoxymethoxy)-4,6,8-trimethylnonan-5-one aldol adducts were confirmed by NMR analysis of 12 acetonide derivatives prepared from the corresponding 5,7-syn diols. Examination of the NMR data for the above set of aldol adducts revealed consistent trends that were exploited to assign the relative configurations of 13 diastereomeric 2-(2-ethyl-1,3-dioxolan-2-yl)-7-hydroxy-3-(triethylsilyloxy)-4,6,8-trimethylnonan-5-one aldol adducts.

(5E)-Dimethyl 2-bromo-methyl-5-cyclo-hexyl-imino-2-phenyl-2,5-dihydro-furan-3,4-dicarboxyl-ate.

The mol-ecule of the title compound, C(21)H(24)BrNO(5), has a planar furan ring [maximum deviation = 0.025 (3) Å]. The carboxy-methyl group in the 3-position is nearly coplanar with this ring [dihedral angle = 7.9 (1)°], whereas that in the 4-position is nearly perpendicular to it [dihedral angle = 78.9 (1) Å].

1-(2-Eth-oxy-2-methyl-2H-chromen-3-yl)ethanone.

The Csp(3) atom of the chromenyl fused-ring system in the title compound, C(14)H(16)O(3), deviates by 0.407 (2) Šfrom the plane of the other atoms (r.m.s. deviation = 0.041 Å). The eth-oxy substituent occupies a pseudo-axial position.