The Renaissance of Zinc Carbenoid in Stereoselective Synthesis in Acyclic Systems

Abstract

In the last few decades we have witnessed the renaissance of zinc carbenoid in acyclic stereoselective synthesis. From the pioneering work of Simmons and Smith that led to a myriad of beautiful enantioselective cyclopropanations of alkenes, zinc carbenoid is again at the center of interest, but this time for the acyclic control of selectivity in allylation reactions. A straightforward method, utilizing the dual characteristics of zinc carbenoid serving both as an electrophile and as a nucleophile, has been recently developed for the preparation of various 3,3-disubstituted allylzinc species that react with various carbonyl and imine moieties to give homoallyl alcohols and amines, respectively, with very high diastereoselectivity. In a one-pot operation, three new carbon−carbon bonds as well as two new sp 3 stereogenic centers were formed, including the formation of the challenging all-carbon quaternary stereogenic centers.

Stereodefined acyclic trisubstituted metal enolates towards the asymmetric formation of quaternary carbon stereocentres

“…69 The electrophilic nature of these species was the subject of several studies and was summarized in a few reviews 66,69,70 and research papers. Usually, oxenoids oxidize vinyl metal into metal enolates with retention of configuration of the initial stereochemistry.…”

[Li2{CH2S(O)Ph}2(TMEDA)2] – An α-sulfinyl-functionalized methyllithium carbenoid

“…Solvents (diethyl ether, n-pentane, tetrahydrofuran, THF-d 8 , toluene-d 8 ) were dried over Na/benzophenone and freshly distilled prior to use. NMR spectra ( 1 H, 13 C, 7 Li) were recorded, if not otherwise stated, at 27°C on a Varian VNMRS 400 spectrometer, operating at 400 MHz for 1 H, 100 MHz for 13 C and 156 MHz for 7 Li. 1 H and 13 C chemical shifts are relative to THF-d 8 signals (d H = 1.72, d C = 67.21) as internal references; 7 Li NMR spectra were referenced to a solution of LiCl in D 2 O (external; d Li = 0.00).…”

“…NMR spectra ( 1 H, 13 C, 7 Li) were recorded, if not otherwise stated, at 27°C on a Varian VNMRS 400 spectrometer, operating at 400 MHz for 1 H, 100 MHz for 13 C and 156 MHz for 7 Li. 1 H and 13 C chemical shifts are relative to THF-d 8 signals (d H = 1.72, d C = 67.21) as internal references; 7 Li NMR spectra were referenced to a solution of LiCl in D 2 O (external; d Li = 0.00). The DOSY experiment was performed under VNMRJ 3.0 and equipped with a 5 mm PFG One NMR probe, z-gradient and temperature unit (27°C).…”

“…It is recognized that carbenes were and still are useful intermediates in organic syntheses [1][2][3][4][5][6] as also carbenoids [7][8][9][10][11][12][13]. Unlike carbenes, which preferentially react as electrophiles, lithium carbenoids possess generally an ambiphilic behavior, so that on the one hand a typical electrophilic and on the other a nucleophilic (carbanionic) reactivity can be observed (cf.…”

Iridium-Catalyzed C–C Coupling of a Simple Propargyl Ether with Primary Alcohols: Enantioselective Homoaldol Addition via Redox-Triggered (Z)-Siloxyallylation

“…3 By merging the characteristics of carbonyl addition and transfer hydrogenation in this way, the direct conversion of lower alcohols to higher alcohols is achieved in the absence of stoichiometric metals or discrete alcohol-to-carbonyl redox reactions. 3 For example, in the context of carbonyl allylation and crotylation, 4,5 these concepts have enabled a progression from the use of chiral allyl- and crotylmetal reagents to direct site-selective catalytic asymmetric conversions of primary alcohols to secondary homoallylic alcohols using abundant commodity chemical feedstocks, such as allyl acetate 6 or butadiene. 7 …”