Mobilizing Cu(I) for Carbon−Carbon Bond Forming Catalysis in the Presence of Thiolate. Chemical Mimicking of Metallothioneins

Abstract

Copper(I) is rendered catalytically viable in the presence of thiolate by the design of a small molecule chemical analogue of the metallothionein system in which an NÀO reactant serves the same conceptual purpose of the SÀS reactant of the biological system.

Nickel-Catalyzed Synthesis of Ketones from Alkyl Halides and Acid Chlorides: Preparation of Ethyl 4-Oxododecanoate

“…2 While both of these protocols are effective, the organometallic reagents can be limiting with complex, functionalized molecules. More recently, cross-coupling methods based upon the less reactive alkyltin, 4 alkylzinc, 5,6 dialkylzinc, 7 or alkylboron 8 reagents have been developed.…”

Stereocontrolled Synthesis of α-Amino-α′-alkoxy Ketones by a Copper-Catalyzed Cross-Coupling of Peptidic Thiol Esters and α-Alkoxyalkylstannanes

“…11 Peptidic ketones can also be prepared in high enantiopurity from the same substrates by two novel, Cu-only catalyzed reaction systems, one using an aerobic recycle pathway 12 and the other an anaerobic pathway that mimics the release of Cu from the metallothionein family of proteins. 13 …”

“…The current reaction system requires only catalytic Cu and proceeds without a “second cycle” designed into the catalysis to retain an active form of Cu. 13 …”

Asymmetric Synthesis of Isothiazoles through Cu Catalysis: Direct Catalytic Asymmetric Conjugate Addition of Allyl Cyanide to α,β‐Unsaturated Thioamides

“…[21] The amount of TEMPO could be reduced to 0.1 equiv and no reaction proceeded in the absence of CuOTf (Table 3, entries 7 and 8). [22] Although intermediate 8 a (or its protonated form) was not isolated, a two-step reaction sequence using iPrMgBr and then CuOTf for the reaction of N,Ndibenzylthioacetamide and benzonitrile afforded isothiazole 10 via intermediate 11, [23] thus suggesting that isothiazole 7 a was likely formed through 8 a [Eq. (1)].…”

“…(1)]. [24] The Cu-catalyzed isothiazole-forming reaction was applicable to other conjugate addition products (3) to furnish enantioenriched fused isothiazoles (Scheme 3). However, the hydrogenated substrate 3 a' did not provide the corresponding isothiazole 7 a', thus suggesting that the conformational restriction by a Zconfigured olefin is indispensable to the initial 6-exo-dig cyclization [Eq.…”