Study on the coupling of acyclic esters with alkenes – the synthesis of 2-(2-hydroxyalkyl)cyclopropanols via cascade cyclization using allylsamarium bromide

Abstract

The radical cyclization between aliphatic acyclic esters and alkenes was achieved unprecedentedly in the presence of allylsamarium bromide with HMPA and H(2)O as additives. The cascade radical cyclization-ring-opening-anionic cyclization allowed facile and efficient access to 2-(2-hydroxyalkyl)cyclopropanols from readily available materials.

Cyclopentane Formation from Flexible Precursors Using Samarium(II) Reagents

“…A p ‐tolyl‐substituted ketone cyclized to give cyclopentane product 11d in 54 % yield. Electron‐rich substrates were competent in the cyclization with the p ‐methoxy derivative providing product 11e in 64 % yield and m ‐methoxy ketone giving β‐hydroxyketone 11f in 53 % yield . A heteroaromatic derivative was also shown to undergo the Sm II ‐promoted intramolecular Reformatsky aldol reaction with a thiophene derivative cyclizing to provide product 11g in 54 % yield (entry 6).…”

Additive Tuned Selective Synthesis of Bicyclo[3.3.0]octan-1-ols and Bicyclo[3.1.0]hexan-1-ols Mediated by AllylSmBr

“…The control experiment showed, in the absence of HMPA, allylSmBr was strongly nucleophilic and its reaction with 1a would give the diallylated 3a almost quantitatively (Table , entry 6). Besides, it is interesting to find the coexistence of H 2 O (1.6 equiv) would afford 4a as the major product, following an “ester–alkene” coupling cascade cyclization. , At the same time, 2a was only formed in a trace amount (Table , entry 7) and 3a was not observed, indicating the reducing potential of allylSmBr may be further facilitated by the coexistence of the proton source, and at the same time its nucleophilicity was further diminished. When a mixture of 1a and H 2 O was added dropwise to the allylSmBr/HMPA, a mixture of 2a (40%) and 4a (51%) was obtained and again the formation of 3a was not observed (entry 8).…”

“…With MeOH or H 2 O as an additive, a variety of carbonyl compounds could undergo the pinacol coupling promoted by allylSmBr, instead of being transformed into homoallylic alcohols . Furthermore, the unique reductive coupling ability of allylSmBr has been demonstrated by using HMPA/H 2 O or HMPA/CuCl 2 .2H 2 O as coadditives; thus, the homoallylic esters were transformed into 2-(2-hydroxy­alkyl)­cyclo­propanols and 2-(2-hydroxy­ethyl)­bicycle [2.1.1]­hexan-1-ols in moderate to good yields with good to excellent diastereoselectivities. In addition, the allylSmBr/HMPA/CH 3 SO 3 H system has recently been applied in the preparation of oxobicyclo­[3.1.0]­hexane-1-ols via the “ester–alkene” coupling/cyclization cascade of α-allyloxy esters …”

Allylsamarium Bromide-Mediated Cascade Cyclization of Homoallylic Esters. Synthesis of 2-(2-Hydroxyalkyl)cyclopropanols and 2-(2-Hydroxyethyl)bicyclo[2.1.1]hexan-1-ols

“…During the preliminary studies in our previous work, homoallylic alcohol acetate 1a was employed as the model substrate in our initial attempt to investigate the reductive coupling between an acyclic ester group and an alkene moiety. Without any additive, the use of 2.2 equiv of allylSmBr afforded 1-phenylbut-3-en-1-ol 2a in 86% yield (Scheme ).…”

“…In this paper, we report the allylSmBr-promoted intramolecular reductive coupling of the aliphatic esters of homoallylic alcohols in the presence of appropriate additives. The reaction afforded a facile and diastereoselective synthesis of 2-(2-hydroxyalkyl)cyclopropanols and 2-(2-hydroxyethyl)bicyclo[2.1.1]hexan-1-ols from readily available materials.…”