Enantioselective Addition of Alkynyl Ketones to Nitroolefins Assisted by Brønsted Base/H‐Bonding Catalysis

Abstract

Various sets of enolizable alkynyl ketones (including methyl ynones with α‐aryl, α‐alkenyl, and α‐alkoxy groups) were able to react smoothly with nitroolefins with the assistance of bifunctional Brønsted base/H‐bond catalysts to provide adducts with two consecutive tertiary stereocenters in a highly diastereo‐ and enantioselective fashion. Further transformation of the obtained adducts into optically active acyclic and polycyclic molecules, including some with intricate carbon skeletons, was also demonstrated.

Extended Enolates: Versatile Intermediates for Asymmetric C‐H Functionalization via Noncovalent Catalysis

“…While unsubstituted allyl ketones 99 (R 1 , R 2 =H) invariably led to the MBH‐type products 101 via spontaneous double bond isomerization, adducts from β‐substituted ketones (R 1 ≠H) showed to be resistant towards such isomerization, affording 100 as a mixture of diastereomers (Scheme 26). In addition, the reaction outcome of γ‐substituted ketones 99 (R 1 =H, R 2 ≠H) was catalyst‐dependent: catalyst C11 led to mixtures of both 100 and 101 , but the newly developed bulky catalyst C12 led to nonisomerized product 100 cleanly [72] …”

“…In addition, the reaction outcome of γ‐substituted ketones 99 (R 1 =H, R 2 ≠H) was catalyst‐dependent: catalyst C11 led to mixtures of both 100 and 101 , but the newly developed bulky catalyst C12 led to nonisomerized product 100 cleanly. [72] …”

“…In addition, the reaction outcome of γ-substituted ketones 99 (R 1 = H, R 2 ¼ 6 H) was catalyst-dependent: catalyst C11 led to mixtures of both 100 and 101, but the newly developed bulky catalyst C12 led to nonisomerized product 100 cleanly. [72] C α selective addition of transiently generated acyclic ketone dienolates is prevalent in reactions with activated ketimines, as described by Ma group. [73] Using nonsymmetrical thiourea catalysts C13, the Mannich reaction between aryl allyl ketones 82 and cyclic N-sulfonyl iminoesters 102 afforded adducts 103 with high yields and selectivities (Scheme 27).…”

Regioselective α-addition of vinylogous α-ketoester enolate in organocatalytic asymmetric Michael reactions: enantioselective synthesis of Rauhut–Currier type products

“…10 a C–C bond formation at the α-position of “dienolates” or their equivalent “dienamine” intermediate has also been achieved. 10 In this context, several methods were established for taming the issue of regioselectivity in synthetic chemistry, especially in asymmetric organocatalysis. For example, steric shielding of C γ -position of unsaturated aldehydes is one of the used strategies for achieving α-regioselectivity of vinylogous Michael reaction through dienamine catalysis (Scheme 1b, left).…”

Catalytic Asymmetric Michael Reaction of Methyl Alkynyl Ketone Catalyzed by Diphenylprolinol Silyl Ether

“…Ramachary reported the reaction of methyl alkynyl ketone with α,α-doubly activated alkene to afford a domino Michael/Michael product without isolation of a Michael product (eq ). − Instead of methyl alkynyl ketones, activated methyl alkynyl ketones such as alkoxycarbonyl, aryl, vinyl, or alkoxy-substituted methyl alkynyl ketones − are reported to react with nitroalkene, catalyzed by bifunctional Brønsted base/H-bond catalyst, to afford the Michael products with excellent enantioselectivity (eq 2 and 3). There are no reports of the asymmetric Michael reaction of methyl alkynyl ketone itself as a nucleophile, even in the field of organocatalysis. …”