Catalytic Asymmetric Acyl Halide−Aldehyde Cyclocondensations. A Strategy for Enantioselective Catalyzed Cross Aldol Reactions

Lewis Base Catalysis in Organic Synthesis

“…An excellent illustration of the enhanced electrophilic reactivity of a hypervalent intermediate comes from the work of Nelson et al on tetracoordinate aluminum complexes (Scheme 48). [196] In studies of [2+2] cycloadditions, it was found that neutral tetracoordinate chiral aluminum complexes such as 147 mediate reactions that had earlier been performed with the highly electrophilic aluminum species Al(SbF 6 ) 3 with comparable levels of activity. [197] Illustrations of the enhanced nucleophilic reactivity of hypervalent species are found in the formation of silicates from trialkylsilyl reagents that lead to myriad carbon-carbon bond-forming reactions (see the next section).…”

Synthetic Strategies Employed for the Construction of Fostriecin and Related Natural Products

“…274 This reaction proceeds in 67% yield and in 78–83% ee. This provided the substrate for Johnson’s key transformation between silyl glyoxylate 461 (synthesized in two steps and in 82% yield from benzyl diazoacetate 275 ), Reformatsky reagent 462 , and β -lactone 460 .…”

“…273 This strategy also features a catalytic asymmetric β -lactone forming reaction originally developed by Nelson, 274 which set the absolute stereochemistry of the molecule. Johnson’s strategy also uses a Brown pentenylation, 95,96,204 and a metathesis 91,92 strategy for installation of the α , β -unsaturated lactone.…”

“…The highlight of this synthesis is the first two reactions: the Reformatsky/Claisen condensation 273 and Nelson’s 274 catalytic asymmetric β -lactone formation. These transformations demonstrate the power of addition reactions to quickly assemble molecular complexity.…”

Asymmetric Synthesis of α-Unsubstituted β-Hydroxy Acids

“…The catalytic asymmetric acyl halide -aldehyde cyclocondensation reaction gives highly enantiomerically enriched -lactones (Scheme 20) [64]. -Lactones can be viewed as "activated aldol products" and as such, should give access to a variety of -hydroxy ester or amide adducts by their ring-opening via nucleophilic addition at the carbonyl function.…”