Highly Diastereoselective Preparation of anti-1,2-Diols by Catalytic Addition of Alkynylsilanes to α-Silyloxyaldehydes

Abstract

The catalytic, diastereoselective coupling of α-silyloxy aldehydes and alkynylsilanes catalyzed by a nickel(0) N-heterocyclic carbene complex provides an effective entry to anti-1,2-diols. The scope of couplings and extent of diastereoselection are excellent across a range of substrates.Diastereoselective nucleophilic additions to α-alkoxy aldehydes provide an attractive method for preparation of 1,2-diols. Synthesis of anti-1,2-diols can be achieved by additions to chiral aldehydes following the Felkin model for diastereoselection, although control of stereochemistry can often be a challenge. A number of studies involving alkenylation of α-alkoxy aldehydes illustrate that anti selectivity can sometimes be achieved, but that the results are variable depending upon the precise structure of both the chiral aldehyde and vinyl organometallic. 1,2 Several attractive alternative strategies that rely upon aldol technology have also been developed to avoid these limitations. 3 The nickel-catalyzed addition of aldehydes and alkynes has emerged as a useful way to prepare allylic alcohols in a variety of contexts. 4,5 Several reports of nickel-catalyzed reductive couplings of this class involving highly stereoselective additions to chiral α-alkoxy aldehydes have appeared. 6,7 Absent among the reports involving nickel catalysis is the intermolecular diastereoselective addition of non-aromatic alkynes, terminal alkynes, and silyl alkynes. Additionally, intermolecular additions involving α-alkoxyaldehydes bearing an unbranched substituent at the α-carbon proceeded with modest diastereoselectivity. 6c Given the utility of catalytic couplings of aldehydes and alkynes involving nickel(0) / N-heterocyclic carbene catalysts recently disclosed from our group, 8 we have examined this catalyst formulation in diastereoselective additions of alkynes to α-silyloxyaldehydes. The reaction scope and extent E-mail: jmontg@umich.edu. Although our group previously demonstrated that the structure of an N-heterocyclic carbene ligand can play an important role in determining yield and regioselectivity in nickel-catalyzed aldehyde / alkyne reductive couplings, the current study focused exclusively on reactions involving Ni(COD) 2 and the N-heterocyclic carbene (IMes) derived from imidazolium 1 in THF. From our prior studies, we recognized that silane structure was important in order to select for the desired three component coupling over undesired hydrosilylation of the aldehyde or alkyne moieties. We thus compared the catalytic addition of a TBS-protected silyloxy aldehyde with trimethylsilyl(phenyl)acetylene using various silanes. Due to competing hydrosilylation processes with unhindered silanes, chemical yields with (i-pr) 3 SiH were superior to (t-Bu)Me 2 SiH and Et 3 SiH (Table 1, entries 1-3). We next compared (i-pr) 3 SiHmediated couplings of TMS-propyne with various α-oxyaldehydes (Table 1, entries 4-7). Both diastereoselectivities and yields were only modestly impacted in comparing α-benzyloxy to various α-silyloxy groups, ...

Regioselective Reductive Cross‐Coupling Reactions of Unsymmetrical Alkynes

“…For example, in recently reported Ni-catalyzed reductive coupling reactions of TMS-alkynes with aldehydes (eq 10), the regiochemical course of the reaction is opposite to that previously observed in the related coupling reactions promoted by group IV metals. [11] Here, the major product derives from C–C bond formation proximal to the TMS substituent.…”

Asymmetric Domino Reactions Based on the Use of Chiral Substrates

“…214 In this case, the reaction consisted in a three-component coupling of a chiral a-silyloxyaldehyde with an alkynylsilane in the presence of (i-Pr) 3 SiH as the reducing agent. This domino aldehyde-alkyne reductive coupling process, performed in the presence of Ni(cod) 2 and N-heterocyclic carbene generated from imidazolium, afforded the corresponding protected allylic alcohols in excellent yields and diastereoselectivities of up to 96% de, as shown in Scheme 1.126.…”

Nickel‐Catalyzed Reductive Couplings and Cyclizations

“…Ni(COD) 2 (10 mol%), L reducing agent ( A similar protocol employs α -silyloxyaldehydes with a t -butyldimethylsilyl (TBDMS) protecting group and TMS -protected alkynes [50] . In this protocol, β -unbranched aldehydes afforded the highest level of diastereoselectivity (Scheme 8.26 ).…”