Low-Valent Titanium-Mediated Stereoselective Alkylation of Allylic Alcohols

Abstract

We have developed low-valent titanium-mediated 1,3-transpositive cross-coupling reactions of acyclic and cyclic allylic alcohols for the stereoselective introduction of ethyl, 2-silylethyl, 2-phenethyl, and alkenyl groups. Cross-coupling of an allylic alcohol with a vinylsilane or styrene derivative is particularly noteworthy, as an efficient cross-selective coupling of two alkenes has been elusive. The stereochemistry of the cross-coupling alkylation is consistent with syn addition/beta-elimination.

Stereoselective Alkylation of Allylic Alcohols: Tandem Ethylation and Functionalization

“…This also represents formal cross-coupling reactions between allylic alcohols and terminal olefins bearing useful functional groups with concomitant 1,3-transposition. [3,6] Received: June 22, 2011 Published online: August 26, 2011…”

5.34 Early Transition Metal Mediated Reductive Coupling Reactions

“…Although this process has been demonstrated to be useful for addition of a C 3 -unit to an alkyne, where issues regarding stereoselection are absent, 27,114,115 the class of cross-coupling has only recently been rendered stereoselective in reactions that employ highly substituted allylic alcohols. 116,117 As illustrated in Scheme 48B, hydroxyl-directed cross-coupling provides a means to translate stereochemical information from the allylic alcohol starting material to the intermediate metallacyclopentene. Stereospecific elimination then parlays the stereochemistry of this intermediate to the stereochemistry of the functionalized 1,4-diene product.…”

Metallacycle-mediated cross-coupling in natural product synthesis

“…In a departure from the use of Cp 2 M-based species, and in the context of studies aiming to render the metallacycle-mediated cross-coupling alkoxide-directed, Micalizio and Cha described highly stereoselective alkyne–allylic alcohol coupling processes that established ( E )-disubstituted or ( Z )-trisubstituted alkenes (Figure 11B). 41, 42 Here, reversible docking of the alkene substrate to the preformed metallacyclopropene by Ti–O bond formation is proposed to result in an opportunity for intramolecular carbometalation through a boat-like transition state. Minimization of allylic strain (1,3- or 1,2-) was then rationalized as the means by which one can attain high levels of stereocontrol for the formation of 1,4-dienes containing either an ( E )-disubstituted or ( Z )-trisubstituted alkene.…”