Enantioselective α-Alkenylation of Aldehydes with Boronic Acids via the Synergistic Combination of Copper(II) and Amine Catalysis

Abstract

The enantioselective α-alkenylation of aldehydes has been accomplished using boronic acids via the synergistic combination of copper and chiral amine catalysis. The merger of two highly utilized and robust catalytic systems has allowed for the development of a mild and operationally trivial protocol for the direct formation of α-formyl olefins employing common building blocks for organic synthesis.

Simple Catalytic Mechanism for the Direct Coupling of α-Carbonyls with Functionalized Amines: A One-Step Synthesis of Plavix

“…Toward this end, we have demonstrated the ability of copper(I) to catalyze the α-arylation of enol-silanes in the presence of diaryliodonium salts. 6 Additionally, the synergistic merger of copper(I) catalysis with enamine catalysis has led to the development of methods for the enantioselective α-arylation, 7 α-vinylation, 8 α-oxygenation, 9 and α-trifluoromethylation 10 of aldehyde substrates. On this basis, the proposed mechanism for the carbonyl amination is presented in Scheme 1.…”

Sodium Iodide‐Catalyzed Direct α‐Alkoxylation of Ketones with Alcohols via Oxidation of α‐Iodo Ketone Intermediates

“…[7] For example, the amine-assisted Cucatalyzed oxidative cross-coupling of aldehydes with alkenylboronic acids has been established for the enantioselective a-alkenylation of aldehydes. [8] On the other hand, hypervalent iodine compounds have proved to be versatile reagents for diverse oxidative transformations [9] including a-functionalizations of carbonyl compounds. [10] On the basis of the advances in using hypervalent iodine reagents for organic syntheses, aryl iodide-or iodide salt-catalyzed oxidative transformations have recently been developed, in which hypervalent iodine intermediates are in-situ generated in catalytic processes.…”

Oxidative Coupling of Aryl Boron Reagents with sp3‐Carbon Nucleophiles: The Enolate Chan–Evans–Lam Reaction

“…[8][9][10] Indeed, in comparison to heteroatom nucleophiles,r eports of copper promoting CÀC bond-forming reactions with aryl boron reagents under oxidative conditions remain sparse. [11,12] To the best of our knowledge,enamine annulation [13] and vinylation [14] represent the closest known reports towards an enolate Chan-EvansLam reaction. Currently available oxidative arylation strategies employing organoboron reagents and activated methylenes require stoichiometric amounts of Pb(OAc) 4 in combination with mercury additives.…”

“…[2,14] Theu se of aryl boronic anhydrides (boroxines), however, provided ab reakthrough in reactivity (Table 1A). Under standard reaction conditions,b oth aryl boronic acids Angewandte and pinacol boronic esters provided only trace conversion into the desired arylated malonate product (2 %a nd 7%, respectively), while the aryl boroxine provided excellent yields (86 %) and minimal side-product formation.…”