Catalyst-Controlled Regioselective Nitrosocarbonyl Aldol Reaction of Deconjugated Butenolides

Abstract

An unprecedented regiodivergent nitrosocarbonyl aldol reaction of γ-substituted deconjugated butenolides is described. While Lewis base catalyst quinidine leveraged O-selective nitrosocarbonyl aldol reaction exclusively at the γ-position of deconjugated butenolides to produce γ-aminoxylation products, Lewis acid catalyst Cu­(OTf)2 steered the competitive N-selective nitrosocarbonyl aldol reaction at the β-position, resulting in heterodifunctionalized butenolides. Both processes were amenable to a broad range of substrates and scalable, while the latter one represents a rare example of one-pot hetero-β,γ-difunctionalization of butenolide scaffolds.

Regioselective Nitrosocarbonyl Aldol Reaction of Deconjugated Butyrolactams: Synthesis of γ‐Heterosubstituted α,β‐Unsaturated γ‐Lactams

“…Based on earlier reports, [8,11d] a possible reaction mechanism is depicted in Scheme 4c. Deprotonation of deconjugated butyrolactam 1 with quinidine catalyst produces dienolate A which then reacts with in situ generated nitrosocarbonyl species B (MnO 2 oxidation of hydroxamic acid 2 ) to give intermediate C .…”

Organocatalyzed Regioselective α,γ-Difunctionalization of Deconjugated Butenolides: Synthesis of Butyrolactone–Butyrolactam Hybrid Molecules

“…We also reported heterodifunctionalization via nitrosocarbonyl aldol type reaction of deconjugated butyrolactones. 5 However, these processes are restricted to regio- and stereoselective β,γ-difunctionalization of butyrolactones, while similar difunctionalizations involving other positions of deconjugated butyrolactones are scarce. In this direction, α,γ-difunctionalization is increasingly challenging as it necessitates site-selective functionalization in a specific sequence – initial monofunctionalization at the α-position followed by vinylogous γ-functionalization.…”

Asymmetric aldol reaction catalyzed by amino acid tetrapeptides (l-Pro-l-Pro-l-Phe-l-Phe-OMe)

“…[22][23][24] During the reaction, L-Pro can form stable zwitterion intermediates with the substrate, effectively improving the enantioselectivity of the product. 22,[25][26][27] As a chiral inducer with a loose spatial structure, L-Phe-L-Phe-OMe can enhance the chiral induction of L-Pro, further improving the enantioselectivity. 28 Therefore, it is of research value to select an L-phenylalanine dipeptide and a proline dipeptide as the modules for tetrapeptide catalysts.…”