Regioselective Alkyl and Alkynyl Substitution Reactions of Epoxy Alcohols by the Use of Organoaluminum Ate Complexes:  Regiochemical Reversal of Nucleophilic Substitution Reactions

Abstract

Unprecedented nucleophilic substitution reactions of 2,3-epoxy-1-alkanols with alkyl- and alkynylaluminum ate complexes have been studied and demonstrated to occur at the C2 position with extremely high stereoselectivity, i.e., with exactly reversed regioselectivity to that obtained in the substitution reactions by normal organoaluminum reagents, resulting in the formation of the C2-alkyl and C2-alkynyl substitution products in excellent yields.

Ring-opening of 2,3-epoxy-1-propanol with R3Al: Unprecedented regiochemical switching simply achieved by changing alkyl substituents of aluminium reagent

“…Similar selectivity have been observed for the nucleophile addition to epoxy alcohols with R 2 AlN 3 [3a,3d,3e] or R 2 AlCN reagents [4]. Only recently, a reversal of regioselectivity was revealed for the alkylation of 2,3-epoxy alcohols with R 3 Al/BuLi system, where R = Me or Et [5]. We have recently initiated systematic studies on the selective alkyl addition to 2,3-epoxy alcohols choosing the group 13 metal alkyls and rac-2,3-epoxy-1-propanol (epol-H) as a simple model system.…”

Modular Total Synthesis of Rhizopodin: A Highly Potent G‐Actin Dimerizing Macrolide

“…With compound 66 in hand, we were confident of establishing conditions for a selective copper‐mediated opening of the epoxide with one of the many reported methyl nucleophiles to gain access to compound 67 42. Thus, we examined various copper(I) sources (CuI, CuCN) with different nucleophiles (MeLi, MeMgCl, MeMgBr), as well as the reagent combination n BuLi/AlMe 3 , which was only recently described 43. However, disappointingly, all of these conditions either resulted in decomposition (CuI/MeMgBr) or no conversion, so we had to revise our strategy.…”

“…[42] Thus, we examined various copper(I) sources (CuI, CuCN) with different nucleophiles (MeLi, MeMgCl, MeMgBr), as well as the reagent combination nBuLi/AlMe 3 , which was only recently described. [43] However, disappointingly, all of these conditions either resulted in decomposition (CuI/MeMgBr) or no conversion, so we had to revise our strategy.…”

Stereoselective VO(acac)2 catalyzed epoxidation of acyclic homoallylic diols. Complementary preparation of C2-syn-3,4-epoxy alcohols

“…The corresponding anti,trans homoallylic diol 5b was prepared in 77% yield by the regioselective epoxide ring opening of 4- cis using the diethylpropynylalanate conditions developed by Miyashita13 followed by the sodium/ammonia reduction of the resulting alkynol (Scheme 3). The synthesis of the free primary homoallylic alcohols 8a and 8b was achieved by the diprotection of 5a and 5b as the TBS ethers, followed by selective deprotection of the primary TBS group.…”