γ‐Silyl Group Effect in Hydroalumination and Carbolithiation of Propargylic Alcohols

Abstract

The hydrometalation reaction of an alkynyl group is a valuable process, not only for functionalized alkene synthesis but also for alkenyl metal preparations.[1] Among the numerous variants of this class of reaction, hydroalumination of propargylic alcohols is especially well utilized in many facets of organic synthesis owing to its promising chemo-and stereoselectivity [Eq. (1); L = ligand, E = electrophile]. [2,3] Herein, we report a noticeable accelerating effect of a gsilyl substituent on the hydroalumination reaction, an effect that can substantially enhance the synthetic utility of this classical transformation. By proper choice of the silyl group, highly group-selective functionalization in polyalkynyl alcohols A has been accomplished by overcoming the steric influences, to provide valuable multifunctionalized alcohols B through hydroalumination and also carbolithiation [Eq. (2)].We have found this unprecedented silyl effect during the course of our synthetic study of zaragozic acid A.[4] As one of the key steps in this total synthesis, we faced the problem of group-selective functionalization of intermediate 1, which has three alkynyl groups on C4 and C5 [Eq. (3); Bn = benzyl, TBDPS = tert-butyldiphenylsilyl, TBS = tert-butyldimethylsilyl, TMS = trimethylsilyl]. Surprisingly enough, hydroalumination of alcohol 1 with sodium bis(2-methoxyethoxy) aluminum hydride (Red-Al) provides vinylsilane 2 exclusively. [5] Our purpose for the total synthesis was achieved by this group-selective transformation; however, a question that immediately arose was why the reaction preferentially occurred at the alkyne substituted with the bulkier TBDPS group, rather than one substituted with the less bulky TMS group.[6] At an earlier stage, we suspected an influence of the multiple oxy functionalities on 1 to be the origin of the peculiar selectivity; these functionalities may exert chelation control on the aluminum reagent.[7] Thus, in order to eliminate this confusing factor, we examined a competitive hydroalumination in a series of simplified 1,1-bis(alkynyl) alcohols 3 bearing TBDPS and TMS groups at the g and g' positions (Table 1).The reaction of sec-alcohol 3 a (R = H) with Red-Al in toluene at 0 8C provides vinylsilane (E)-4 a (95 %) predominantly, along with a trace amount of (E)-5 a (3 %; TBDPS side/TMS side 97:3; Table 1, entry 1).[8] Similar selectivity was [a]

Efficient Synthesis of Methylenetetrahydrofurans and Methylenepyrrolidines by Formal [3+2] Cycloadditions of Propargyl Substrates

“…Then, silicon‐substituted propargyl alcohols were investigated next. A silicon group may activate the alkyne group towards electrophilic reactions, as indicated by some literature precedent, for example, the reactivity of silyl‐substituted propargyl alcohols versus alkyl propargyl alcohols in hydroalumination reactions with Re–Al 25. The silyl group in the resulting cyclized products with a vinylsilane moiety can be used for further synthetic elaboration 26.…”

Platinum‐Catalyzed Hydrosilylations of Internal Alkynes: Harnessing Substituent Effects to Achieve High Regioselectivity

“…The electronic effect that dictates the regioselectivity is obtainable through 13 C NMR data, which we note can be correlated with computational predictions. [24] Vinylsilanes also represent useful synthetic handles that can be readily transformed while maintaining geometrical integrity. Given both the practicality and predictability of the process in combination with the overall utility of the product silanes, platinum-catalyzed hydrosilylations of internal alkynes should find widespread utility in synthetic applications.…”