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

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 beta-boryl-alpha-aryl-alpha-alkenylcopper species, whose subsequent reaction with secondary allyl phosphates provides gamma-(4E)-selective boron-substituted 1,4-dienes, and with primary allyl phosphates provided alpha-selective boron-substituted 1,4-dienes. On the other hand, the alpha-boryl-alpha-aryl-beta-alkenylcopper species formed as a minor intermediate from aryl alkyl acetylenes and the beta-borylalkenylcopper species formed from dialkyl acetylenes show poor regioselectivity with respect to the secondary allyl phosphate and produce a mixture of alpha- and gamma-selective boron-substituted 1,4-dienes. However, their reactions with the primary allyl phosphate are highly gamma-selective. For all of the alpha-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.