Substrate-Controlled Regio- and Stereoselective Synthesis of Boron-Substituted 1,4-Dienes via Copper-Catalyzed Boryl–Allylation of Alkynes with Allyl Phosphates and Bis(pinacolato)diboron

Abstract

Boron-substituted 1,4-dienes are versatile building blocks for the synthesis of 1,4-dienes (skipped alkenes), a common motif in bioactive natural products, because of their utility in the Suzuki–Miyaura coupling reaction and conjugate additions. A method for the synthesis of boron-substituted 1,4-dienes by means of copper-catalyzed boryl–allylation of alkynes with allyl phosphate and bis(pinacolato)diboron has been developed. The regioselectivity with respect to the alkyne and allyl phosphate depends on the structures of both the alkyne and the allyl phosphate. For alkynes bearing at least one aryl substituent, addition of borylcopper to the alkyne mainly generates a β-boryl-α-aryl-α-alkenylcopper species, whose subsequent reaction with secondary allyl phosphates provides γ-(4E)-selective boron-substituted 1,4-dienes, and with primary allyl phosphates provided α-selective boron-substituted 1,4-dienes. On the other hand, the α-boryl-α-aryl-β-alkenylcopper species formed as a minor intermediate from aryl alkyl acetylenes and the β-borylalkenylcopper species formed from dialkyl acetylenes show poor regioselectivity with respect to the secondary allyl phosphate and produce a mixture of α- and γ-selective boron-substituted 1,4-dienes. However, their reactions with the primary allyl phosphate are highly γ-selective. For all of the α-selective reactions, the configuration of the C═C bond of the allyl phosphate was retained in the products. The palladium-catalyzed cross-coupling of boron-substituted 1,4-dienes and aromatic, alkenyl, and alkynyl halides gave polyenes or enynes in 68%–95% yield, demonstrating that these boron-substituted 1,4-dienes are versatile building blocks for the synthesis of 1,4-dienes.