Stereoselective Synthesis of α‐Allenols by Rhodium‐Catalyzed Reaction of Alkynyl Oxiranes with Arylboronic Acids

Abstract

Allenes constitute an important class of building blocks possessing axial chirality as well as unique reactivities.[1] The S N 2'-type substitution of propargylic alcohol derivatives with organometallic reagents is one of the most reliable procedures for the stereoselective preparation of substituted allenes.[2] We previously described the rhodium-catalyzed substitution reaction of propargylic acetates with phenylboronic acid, wherein the resulting alkenylrhodium(I) intermediate underwent b-oxygen elimination to afford a trisubstituted allene. [3] In an extension of this work we set out to examine the use of alkynyl oxiranes as acceptors for arylboronic acids owing to the considerable interest in the resulting a-allenols as building blocks for the construction of oxygenated heterocycles of biological and pharmacological relevance.[4] We report herein on the rhodium-catalyzed reaction of alkynyl oxiranes with arylboronic acids which yields a-allenols with excellent diastereoselectivity.Alkynyl oxirane 1 a (1.0 equiv) was treated with phenylboronic acid (2 a, 1.5 equiv) in the presence of [{RhCl(nbd)} 2 ] (5 mol % of Rh, nbd = norborna-2,5-diene) [5] and KOH (0.6 equiv) in THF (0.1m) at room temperature. The reaction was completed in 2 h, and an extractive workup followed by chromatographic isolation afforded the a-allenol 3 aa in 81 % yield with excellent diastereoselectivity (syn/anti = 99:1)

NiI Catalyzes the Regioselective Cross‐Coupling of Alkylzinc Halides and Propargyl Bromides to Allenes

“…[1] Pd, [2] Cu, [3] Rh, [4] Fe, [5] and Ni [6] derivativesh ave been used as catalysts in these reactions for the activation of propargylh alides, esters, carbonates,a nd phosphonates. [1] Pd, [2] Cu, [3] Rh, [4] Fe, [5] and Ni [6] derivativesh ave been used as catalysts in these reactions for the activation of propargylh alides, esters, carbonates,a nd phosphonates.…”

Enantiodivergent Synthesis of Allenes by Point‐to‐Axial Chirality Transfer

“…[5] Whilst broad-ranging,t his method can result in lower enantiospecificity for tetrasubstituted allenes, for which only ah andful of enantioselective preparative methods exist. [6] Afurther limitation of such strategies is that if the opposite enantiomer of the allene is desired, then the synthesis must be repeated by first preparing the enantiomeric propargylic electrophile. [7] We envisaged ac omplementary strategy in which an alkenyl boronic ester bearing an a-leaving group (LG 1 )i s homologated with an enantioenriched lithium carbenoid (Scheme 1B).…”

“…[6] We therefore set out to determine whether our method could target such materials.Accordingly, allylic boronic ester 34 was synthesized in high enantioselectivity by homologation of at etrasubstituted alkenyl boronic ester with alithiated secondary benzylic carbamate.W ewere delighted to find that 34 underwent elimination to form either enantiomer of the corresponding tetrasubstituted allene,(M)-35 and (P)-35,ingood yields and excellent enantiospecificity (98:2 e.r. and 95:5 e.r.,respectively).…”

Stereoselective Synthesis of Conjugated Bisallenols as Precursors of Novel Bis(2,5‐dihydrofuran) Derivatives

“…[7] Whereas the iron-catalyzed reaction of bisoxiranes 1 with Grignard reagents, [14] as well as the rhodium-catalyzed S N 2'-substitution with arylboronic acids [15] did not afford any of the desired bisallene, we were pleased to observe a smooth conversion of the bisoxiranes 1 into the bis(a-hydroxyallenes) 2 by reaction with magnesium cuprates in THF. [7d,16] Thus, treatment of the O-methylated bis(propargyloxirane) 1a with the cuprate obtained from isopropyl or tert-butylmagnesium chloride and CuBr·SMe 2 at À65 8C and warming of the reaction mixture to room temperature gave the Scheme 1.…”