Synthesis of γ-, δ-, and ε-Lactams by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)iminoesters

Abstract

Abstract:Highly enantiomerically enriched γ-and δ-lactams have been prepared by a simple and very efficient procedure that involves the asymmetric transfer hydrogenation of N-(tertbutylsulfinyl)iminoesters followed by desulfinylation of the nitrogen atom and spontaneous cyclization to the desired lactams during the basic work-up procedure. Five-and six-membered ring lactams bearing aromatic, heteroaromatic and aliphatic substituents have been obtained in very high yields and ee's up to > 99%. A slight modification of the procedure also allowed the preparation of ε-lactams in good yields and very high enantioselectivities. Both enantiomers of the final lactams could be prepared with equal efficiency by changing the absolute configuration of the sulfinyl chiral auxiliary.

Palladium-Catalyzed Enantioselective Relay Heck Arylation of Enelactams: Accessing α,β-Unsaturated δ-Lactams

“…Although chiral 7-substituted ε -lactams are present in biologically active molecules, 12 few methods are reported for their syntheses. 7b, 13 Compared with the 6-membered enelactam, diminished reactivity of the analogous seven-membered substrate was observed in this reaction wherein generally lower yields were obtained. To address this issue, the catalyst loading was increased to 10 mol % and the arylboronic acid was added in two batches (the second equivalent was added after 24 h).…”

Advances toward the Synthesis of Functionalized γ-Lactams

“…The Guijarro group used a ruthenium catalyst with the achiral 2-amino-2-methylpropan-1-ol ligand to mediate the cyclization of compound 74 to the desired g-lactam 75 in excellent yield and enantiomeric excess (Scheme 17). 27 Aromatic and aliphatic R groups were compatible with the reaction conditions, allowing for the synthesis of a large library of g-lactams. …”

Catalytic Asymmetric Transfer Hydrogenation of Imines: Recent Advances

“…The starting N ‐sulfonyl imino esters 36 (easily prepared from the corresponding keto esters) were submitted to the ATH technology and then to a desulfinylation under acidic conditions to give the lactams 37 through a spontaneous cyclization under the assayed reaction conditions (Scheme ). As it happened, in the chemistry described in Scheme , a change in the configuration of the sulfur atom in the starting N ‐sulfinyl imine gave the opposite configuration in the final product …”

“…As it happened, in the chemistry described in Scheme 6, a change in the configuration of the sulfur atom in the starting N-sulfinyl imine gave the opposite configuration in the final product. [25] N-Phosphinyl ketimines 38 are also suitable starting materials to perform the ATH using the above-mentioned ruthenium complex and the chiral ligand 30, with isopropanol under basic conditions as the reducing agent, affording protected amines 39 with good yields and stereoselectivities (Scheme 8). [26]…”