Regio- and Stereoselectivity in Stannyl- and Silylcupration of Alkynes and Enynes Using Proton Sources

Abstract

Stannylcupration of alkyne 6 was performed using different proton sources such as phenols, alcohols and water; results showed that the cuprate reagent was not affected during the reaction. In all cases tested in presence of a proton source, the vinylstannane 10 corresponding to a trans addition was not produced, while the distal and proximal isomers 8 and 9 resulting from a cis addition were obtained in good yield. The 8/9 ratio was dependent on the reaction temperature, the acidity and the number of equivalents of the proton source. This study was also extended to the stannylcupration of enynes and silylcupration of alkynes and enynes. In total synthesis of natural products, the problem of stereoselective construction of some unsaturated fragments has been resolved in many cases by the use of vinylor dienylstannanes which can be considered as important building blocks in this area. Stereoselective preparation of dienic or trienic systems from vinyl-and/or dienylstannanes was effected via transition-metal catalyzed cross-coupling reactions and/or tinlithium exchange reactions as key reactions which proceeded with total retention of the geometry of vinyl or dienyl precursors.1 For the stereoselective synthesis of (Z)and/or (E)-vinylic stannanes, stannylcuprations2 and Pd-catalyzed hydrostannylations3 of alkynes and enynes have become for the last ten years the most utilized methods in total synthesis. In a preceding work,4 an efficient preparation of pure substituted dienylstannanes such as 3 and 4 (72% and 64% yield respectively) was described by stannylcupration of enynols 1 and 2 using methanol as a proton source while standard conditions did not work (Scheme 1). The same reaction applied to alkynes 5 and 6 [(Bu3Sn)2CuCNLi2, THF/ MeOH (110 equiv.), -10°C, 12h] also only gave the distal stannyl derivatives 7 and 8 in good yields (71% and 70% respectively).