Brønsted Base-Catalyzed Transformation of α,β-Epoxyketones Utilizing [1,2]-Phospha-Brook Rearrangement for the Synthesis of Allylic Alcohols Having a Tetrasubstituted Alkene Moiety

Abstract

A stereoselective transformation of α,β-epoxyketones into alkenylphosphates having a hydroxymethyl group on the β-carbon was established by utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis. The reaction involves the catalytic generation of an α-oxygenated carbanion located at the α-position of an epoxide moiety through the [1,2]-phospha-Brook rearrangement and the following epoxide opening. Further transformation of the alkenylphosphates by the palladium-catalyzed cross-coupling reaction with Grignard reagents provided allylic alcohols having a stereodefined all-carbon tetrasubstituted alkene moiety.

Catalytic Asymmetric Allylic Substitution with Copper(I) Homoenolates Generated from Cyclopropanols

“…Enolization of 3 aa with LDA and subsequent esterification delivered ( Z )‐enol phosphate 6 in 79 % yield with 11/1 Z / E ratio. Further transformations of alkenylphosphate 6 by the palladium‐catalyzed cross‐coupling reaction with Grignard reagents [16] provided dienes 7 in 87 % yield and 8 in 76 % yield, which had stereo‐defined trisubstituted alkene moieties. The terminal olefin moiety in 3 aa was functionalized by Heck reaction to generate internal olefin 9 in 72 % yield with 6/1 E / Z ratio.…”

Brønsted Base‐Catalyzed Formal Reductive [3+2] Annulation of 4,4,4‐Trifluorocrotonate and α‐Iminoketones

“…Interestingly, the lactam ring opening occurred by treatment of 5 a with diethylphosphite in the presence of 20 mol % P2‐ t Bu in DMF to provide 9 as a single geometrical stereoisomer (Scheme 4 B). [15] The reaction would involves the addition of diethylphosphite to the keto moiety followed by the [1,2]‐phospha‐Brook rearrangement [16, 17] and the subsequent β‐elimination of an amide moiety.…”

Formal Fluorinative Ring Opening of 2-Benzoylpyrrolidines Utilizing [1,2]-Phospha-Brook Rearrangement for Synthesis of 2-Aryl-3-fluoropiperidines

“…In our previous study, we utilized the [1,2]-phospha-Brook rearrangement/β-elimination sequence for the catalytic ring opening of epoxides, in which the release of three-membered ring strain would serve as the driving force. 13 In contrast, the present reaction requires the opening of a stable five-membered ring, and is thus more challenging. 14 On the other hand, the direct transformation of alkenylphosphate into an α-functionalized ketone is rare, and the establishment of a new method for the second step is also essential.…”

“…Once B is protonated by the conjugate acid of catalyst or dialkyl phosphite, its re-entry into the catalytic cycle, or the regeneration of B by the direct deprotonation, would be difficult because of the low acidity of the corresponding protonated compound. In our previous study, we utilized the [1,2]-phospha-Brook rearrangement/β-elimination sequence for the catalytic ring opening of epoxides, in which the release of three-membered ring strain would serve as the driving force . In contrast, the present reaction requires the opening of a stable five-membered ring, and is thus more challenging .…”