Asymmetric synthesis of propargylic alcohols via aldol reaction of aldehydes with ynals promoted by prolinol ether–transition metal–Brønsted acid cooperative catalysis

Abstract

A catalytic and highly stereoselective entry to propargylic alcohols and products derived thereof is reported based on an unprecedented cross-aldol coupling between unmodified aldehydes and ynals. The method requires an amine-metal salt-Brønsted acid ternary catalyst system and implies synergistic activation of the donor aldehyde via enamine and of the acceptor carbonyl via unique and reversible metal-alkyne complexation. Specifically, by using a combined a,a-dialkylprolinol silyl ether-CuI-PhCO 2 H catalyst system, remarkably high levels of diastereo-and enantioselectivity (anti/syn up to >20 : 1, ee up to >99%) are achieved.

Enantioselective Synthesis of the Sex Pheromone of Lichen Moth, Miltochrista calamine, and Its Diastereomer

“…Pd-catalytic hydrogenation of the triple bond in propargylic alco- Letter Synlett hols 12a and 12b afforded the target sex pheromone 1a and its diastereomer 1b with 93% and 91% yield, respectively. 27,28 The NMR spectrum and specific rotation of 1a and 1b were consistent with the literature value. 5 In summary, we have developed a new and efficient asymmetric synthesis of Miltochrista calamine sex pheromone and its diastereomer.…”

Diaryl Prolinols in Stereoselective Catalysis and Synthesis: An Update

“…In this context, it is important to mention the contemporary work reported by Palomo and co‐authors, who developed an alternative methodology to accomplish the asymmetric direct cross‐aldol reaction of aldehydes with ynals. The reaction is promoted by prolinol ether 1 e ‐transition metal‐Brønsted acid cooperative catalysis (Scheme b) . They speculated that ynals are particularly difficult substrates to achieve stereoselectivity, given their linear shape.…”

Two‐Pot Synthesis of Chiral 1,3‐syn‐Diols through Asymmetric Organocatalytic Aldol and Wittig Reactions Followed by Domino Hemiacetal/Oxy‐Michael Reactions

“…Olefination also proceeded with a Wittig reagent to provide 6‐aryl‐6‐hydroxyhex‐3‐en‐2‐one in good yield with excellent enantioselectivity and high E selectivity (Table , entries 1–3). The reaction of triethylsilylpropinal or diphenylmethylsilylpropinal with acetaldehyde also proceeded in the presence of diarylprolinol in 1,4‐dioxane to provide the desired α,β‐unsaturated ketone in moderate yield with excellent E selectivity and enantioselectivity after the HWE reaction (Table , entries 5 and 9) . It should be noted that the HWE reaction was employed in some cases because of the low yield of the corresponding Wittig reaction (Table , entries 4, 5, 9, and 10).…”

“…[11a] Olefination also proceeded with aW ittig reagent to provide 6-aryl-6-hydroxyhex-3-en-2-one in good yield with excellent enantioselectivity and high E selectivity ( Table 2, entries 1-3). The reaction of triethylsilylpropinal or diphenylmethylsilylpropinal with acetaldehyde also proceeded in the presence of diarylprolinol 15] It should be noted that the HWE reactionw as employedi ns ome cases because of the lowy ield of the corresponding Wittig reaction (Table 2, entries 4, 5, 9, and 10). The aldol reaction of o-chlorobenzaldehyde and propanal was conducted in the presence of water withouto rganic solvent, and catalyzed by surfactant and proline-conjugated catalyst 7,w hich was developed in our group (Table 2, entry 6).…”