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Letter
Enantioselective Synthesis of Nonracemic Geminal Silylboronates by Pt-Catalyzed Hydrosilylation Adam A. Szymaniak, Chenlong Zhang, John Ryan Coombs, and James P. Morken ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b00221 • Publication Date (Web): 23 Feb 2018 Downloaded from http://pubs.acs.org on February 23, 2018
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ACS Catalysis
Enantioselective Synthesis of Nonracemic Geminal Silylboronates by Pt-Catalyzed Hydrosilylation Adam A. Szymaniak, Chenlong Zhang, John R. Coombs, James P. Morken* Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467 ABSTRACT: A Pt-catalyzed enantioselective hydrosilylation of alkenylboronates is described. This reaction occurs with high regio- and enantioselectivity, providing a convenient route to chiral non-racemic geminal silylboronates. These compounds are useful reagents in stereoselective synthesis. Keywords: Hydrosilylation, Silicon, Boron, Catalysis, Asymmetric
Geminal bimetallic reagents are endowed with distinctive reactivity patterns that allow them to engage in an array of complexity-generating processes. While bimetallic reagents based on Zn, Cr, and Cu species have received steady attention over the past 20-30 years1, recent studies have focused intensely on the synthesis and utility of geminal bis(boronates) in both catalytic and non-catalytic processes.2 In this regard, the utility of symmetric geminal bimetallic reagents (A, Scheme 1) in stereoselective catalysis requires the agency of a catalyst that can not only effect chemical transformation, but can also discriminate the enantiotopic metal groups of the substrate.3 Alternatively, nonracemic, non-symmetrical geminal dimetallic reagents (B, Scheme 1) might engage in a broader array of both catalytic and non-catalytic bond constructions wherein the unique reactivity of each C-M group can be employed to allow differential functionalization of the stereogenic carbon atom. In spite of the significant synthetic utility of nonsymmetric dimetallic reagents, there are few methods available for their catalytic enantioselective preparation. While Hall and Yun established catalytic4 methods that provide access to non-symmetric geminal bis(boronates) (i.e. Scheme 1, B, M1=B(pin); M2=B(dan)), we considered that nonracemic geminal bis(metallates) bearing different metal centers might provide the most diverse reactivity.5 In this connection, pioneering studies by Hoveyda and coworkers6 (Scheme 1, eq. 1) established an efficient catalytic synthesis of nonracemic geminal silylboronates utilizing copper-boron addition to substituted styrenyl silanes. To provide enantiomerically-enriched non-functionalized geminal silylboronates Lan, Liu and coworkers7 introduced a copper-catalyzed aldehyde diboration followed by deoxygenative gem-silylation (Scheme 1, eq. 2). While this latter route is effective, yields are often modest and it requires the use of both a B-B and a B-Si bonded reagent. Herein, we describe a catalytic enantioselective hydrosilylation of readily accessible alkenyl boronates. Importantly, this process applies to a broad range of substrates and can be telescoped directly from alkyne precursors in a tandem hydroboration/hydrosilylation format. For this reason, and because it employs simple silanes and boranes as reagents, the process described herein represents a powerful, scalable route to important synthetic intermediates.
Scheme 1. Utility and Previous Catalytic Syntheses of Nonracemic Geminal Dimetallic Reagents
On the basis of our studies on platinum-catalyzed diboration of alkenyl boronates8 we were prompted to consider the prospects for an aligned Pt-catalyzed hydrosilylation of this substrate class.9 This approach to silylboronate synthesis would have the attractive feature of accommodating a broad array of alkenyl substituents while avoiding the use of diboron and silylboron reagents. Of note, successful development of this process could rely on well-precedented "hydride-first" insertion10 where production of a stable α-boryl-organoplatinum intermediate might dictate reaction regiocontrol. To initiate studies, reaction conditions and catalysts similar to those employed for the diboration of alkenyl boronates were employed, but the diboron reagent was replaced with a silane. Specifically, Pt(dba)3, phosphonite ligand L1, and dimethylphenylsilane were employed in the reaction and found to furnish the hydrosilylation product with complete conversion and high regioselectivity (> 20:1 rr), but only modest enantiocontrol (Table 1, entry 1). Use of less sterically encumbered xylyl-substituted phosphonite L2 (Table 1, entry 2) showed a notable increase in enantioselectivity. Further increases in enanioselectivity were obtained by employing pyrrolidine-
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derived phosphoramidite ligands L3-L4 (Table 1, entries 3-4). With this class of ligands, selectivity is still optimal with meta-substituted arenes on the TADDOL backbone and, of those substituents, 3,5-dialkoxysubstituted ligands L6-L7 (Table 1, entries 6-7) were consistently most effective. (see Supporting Information for full ligand optimization). Analysis of the reaction temperature (Table 1, entry 8 vs. entry 4) showed an increase of enantioselectivity at room temperature, and varying the metal-ligand ratios (Table 1, entries 9-10) were found to be either less selective or efficient. After further analysis of reaction conditions (Table 1, entries 11-17), it was concluded that MTBE as the solvent and L7 as the ligand were optimal conditions to explore the generality of the reaction.
In addition to dimethylphenylsilane, benzyldimethylsilane11 (17) and diphenylmethylsilane (18) also show high reactivity and moderate to good enantioselectivity. Product 18 highlights the ability of the method to be applied to pharmaceutically-relevant problems: after oxidation of the phenyl groups this compound would furnish silane-diol motifs that are often utilized as tetrahedral intermediate bioisosteres.12 It is worth noting that more substituted alkenyl boronates (→19) are not reactive under these conditions. Table 2. Scope of Pt-Catalyzed Enantioselective Hydrosilylation[a]
Table 1. Catalyst Studies in Alkenyl Boronate Hydrosilylation
entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
R= -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -CH2CH2Ph -n-butyl -n-butyl -n-butyl
ligand L1 L2 L3 L4 L5 L6 L7 L4 L4d L4e L6 L6 L6 L6 L7 L7 L7
solvent THF THF THF THF THF THF THF THF THF THF THF MTBE toluene cyclohexane cyclohexane THF MTBE
temp (°C) yield (%)a 70 95 70 96 70 96 70 99 70 99 70 87 70 80 r.t. 14 r.t. 71 r.t.
