Enantioselective ProPhenol-Catalyzed Addition of 1,3-Diynes to Aldehydes to Generate Synthetically Versatile Building Blocks and Diyne Natural Products

Abstract

A highly enantioselective method for the catalytic addition of terminal 1,3-diynes to aldehydes was developed using our dinuclear zinc ProPhenol (1) system. Furthermore, triphenylphosphine oxide was found to interact synergistically with the catalyst to substantially enhance the chiral recognition. The generality of this catalytic transformation was demonstrated with aryl, α,β-unsaturated and saturated aldehydes, of which the latter were previously limited in alkynyl zinc additions. The chiral diynol products are also versatile building blocks that can be readily elaborated; this was illustrated through highly selective trans-hydrosilylations, which enabled the synthesis of a β-hydroxyketone and enyne. Additionally, the development of this method allowed for the rapid total syntheses of several biologically important diynol-containing natural products.

Development of Zn–ProPhenol‐Catalyzed Asymmetric Alkyne Addition: Synthesis of Chiral Propargylic Alcohols

“…[30] It was hypothesized that this Lewis basic group interacts with the dinuclear zinc catalyst and reinforces the chiral pocket created by the ProPhenol ligand. The proposed coordination is supported by the X-ray crystal structure of the ProPhenol dinuclear zinc complex reported by Ding and coworkers (Figure 2).…”

Total Synthesis of Chiral Falcarindiol Analogues Using BINOL-Promoted Alkyne Addition to Aldehydes

“…However, in these reports, the chiral diynols with two or more chiral centers, such as falcarindiol or panaxytriol, were not investigated. Trost et al employed their dinuclear zinc prophenol catalyst to produce chiral terminal diynols, followed by a regioselective ring-opening of the siloxy epoxide to give the (3R,9R,10R)-panaxytriol in high yield [19]. This efficient catalytic system was also applied in the synthesis of minguartynoic acid, which is a kind of polyacetylene chiral alcohol [20].…”

“…The synthetic sequence started from the preparation of the diyne. The intermediate buta-1,3-diyn-1-yltriisopropylsilane (4) was synthesized according to the method described by Trost et al with our modification, as shown in Scheme 1 [19]. 2-Methylbut-3-yn-2-ol (1) was treated with Br2 and aq.…”

Catalytic asymmetric synthesis of (S,4E,15Z)-docosa-4,15-dien-1-yn-3-ol, an antitumor marine natural product

“…The enantioselective addition of the terminal alkynes to aldehydes can give optically active propargyl alcohols directly. [7][8][9] We envisioned that the propargyl alcohol motif of 1 could be formed through this methodology. Herein, we report an efficient enantioselective synthesis of antitumor marine natural product 1 with high enantiomeric purity, which is the first synthesis of 1 via an asymmetric catalytic reaction.…”