Bimetallic Catalytic Asymmetric Tandem Reaction of β‐Alkynyl Ketones to Synthesize 6,6‐Spiroketals

Abstract

The enantioselective tandem reaction of b,g-unsaturated a-ketoesters with b-alkynyl ketones was realized by ab imetallic catalytic system of achiral Au III salt and chiral N,N'-dioxide-Mg II complex. The cycloisomerization of balkynyl ketone and asymmetric intermolecular [4+ +2] cycloaddition with b,g-unsaturated a-ketoesters subsequently occurred, providing an efficient and straightforwarda ccess to chiral multifunctional 6,6-spiroketals in up to 97 %yield, 94 % ee and > 19/1 d.r.Besides,acatalytic cycle was proposed based on the results of control experiments. Scheme 2. Substrate scope for b-alkynyl ketones. Unless otherwise noted, all reactions were performed with Mg(OTf) 2 (2.5 mol %), AuCl 3 (2.5 mol %), l-RaPr 3 (5 mol %), 1a (0.10 mmol), 2b-2o (0.15 mmol), 5 M. S. (30 mg) in DCM (1.0 mL) at 40 8 8Cfor 2d ays. [a] In DCM (0.5 mL) at 40 8 8Cf or 4d ays. Scheme 3. The transformations of the chiral product 3a.Scheme 4. Control experiments and plausible mechanism.

Transition Metal‐Catalyzed Hydroalkoxylation of Alkynes: An Overview

“…Enantioselective selective synthesis of 6,6-spiro-ketals was achieved by Feng and co-workers using a bimetallic catalytic system from o-alkynyl ketone 189 and α,β-unsaturated esters 190 (Scheme 72). [77] The reaction of o-alkynyl ketone 189 and α,β-unsaturated esters 190 with AuCl 3 (2.5 mol %), Mg(OTf) 2 (2.5 mol %) and chiral N, N-dioxide as the ligand (5 mol %), Chemistry-A European Journal furnished corresponding spiro-ketals 191 in good to excellent diastereo-and enantioselectivity. The reaction mechanism involved hydroalkoxylation followed by elimination of α-hydrogen to give exocyclic enol ether Int-ZK, which upon hetero-Diels-Alder cycloaddition reaction afforded desired spiro-ketals.…”

Six-membered ring systems: with O and/or S atoms

“…A wide variety of spirodihydropyran isochromenes were synthesized under dual catalysis of an achiral gold(III) salt and chiral N,N 0 -dioxide-magnesium(II) complex via enantioselective tandem reaction of b,g-unsaturated a-keto esters with b-alkynyl ketones in refluxing dichloromethane. It involves cycloisomerization and intermolecular [4 þ 2] cycloaddition reactions (Scheme 40) (19AGE4017).…”

Catalytic asymmetric Nakamura reaction by gold(I)/chiral N,Nʹ-dioxide-indium(III) or nickel(II) synergistic catalysis

“…However, one of the perceived challenges is that two distinct metals might competitively coordinate with the ligand, as well as potentially affect each other’s catalytic cycles. Recently, chiral N , Nʹ -dioxides/hard Lewis acid complexes developed by our group were found to be good partners with soft metals 47 – 51 in relay catalysis systems. We envisioned that N , Nʹ -dioxide/Lewis acid complex could also be applied to synergistic catalyst system.…”