Total Synthesis of Cryptocaryol A by Enantioselective Iridium‐Catalyzed Alcohol C−H Allylation

Abstract

Less is More The polyketide natural product Cryptocaryol A is prepared in 8 steps via iridium catalyzed enantioselective diol double C-H allylation, which directly generates an acetate-based triketide stereodiad. In 4 previously reported total syntheses, 17-28 steps were required.

Enantioselective Organocatalysis-Based Synthesis of 3-Hydroxy Fatty Acids and Fatty γ-Lactones

“…ether:diethyl ether = 8:2) 0.57; [α] D 20 −17.0 ( c 0.50, CHCl 3 ), [ref. [43], [α] D 20 −18.33 ( c 0.36, CHCl 3 )]; 1 H-NMR (CDCl 3 ) δ 5.90–5.69 (m, 1H, =CH), 5.12–5.04 (m, 2H, =CH 2 ), 3.64–3.53 (m, 1H, C H OH), 2.32–2.03 (m, 3H, C H 2 CH, OH), 1.41–1.09 (m, 28H, 14 × CH 2 ), 0.85 (t, J = 5.8 Hz, 3H, CH 3 ); 13 C-NMR (CDCl 3 ) δ 138.6, 114.6, 71.3, 37.4, 36.4, 31.9, 30.0, 29.7, 29.3, 25.6, 22.6, 14.0; HRMS (ESI) exact mass calculated for [M + Na] + (C 19 H 38 ONa + ) requires m / z 305.2815, found m / z 305.2811.…”

Feedstock Reagents in Metal‐Catalyzed Carbonyl Reductive Coupling: Minimizing Preactivation for Efficiency in Target‐Oriented Synthesis

“…The same C 2 ‐symmetric diol previously required a seven‐step synthesis involving three protecting group manipulations, two separate alcohol oxidations, and two separate carbonyl asymmetric allylborations . As illustrated in concise total syntheses of (+)‐roxaticin, bryostatin 7, cryptocaryol, mandelalide (not shown), and neopeltolide (not shown), this C 2 ‐symmetric diol serves as a powerful building block for polyketide construction. Neopentyl glycol (6.8×10 5 tons yr −1 ) is used extensively in the paints and coatings industry.…”

Feedstock Reagents in Metal‐Catalyzed Carbonyl Reductive Coupling: Minimizing Preactivation for Efficiency in Target‐Oriented Synthesis

“…[31] This "double crotylation" has dramatically simplified the syntheses of other polyketide natural products,s uch as 6-deoxyerythronolide B [17] and zincophorin. [34] As illustrated in concise total syntheses of (+ +)-roxaticin, [35,36] bryostatin 7, [37,38] cryptocaryol, [39,40] mandelalide (not shown), [41] and neopeltolide (not shown), [42,43] this C 2 -symmetric diol serves as ap owerful Scheme 6. [33] The same C 2 -symmetric diol previously required as even-step synthesis involving three protecting group manipulations,two separate alcohol oxidations,a nd two separate carbonyl asymmetric allylborations.…”