An Intramolecular Umpolung Cascade Kukhtin–Ramirez Reaction/Michael Addition-Initiated Cyclization: Stereoselective Synthesis of Tetrasubstituted Cyclopropane Fused 1-Indanones

Abstract

Herein, we disclose a fascinating highly stereoselective P(NMe 2 ) 3 mediated intramolecular deoxygenative umpolung cascade Michael addition-initiated cyclopropanation with a diverse substrate adaptability. This methodology creates a new horizon for expedient access to valuable 6,5,3-fused scaffolds having an all-carbon quaternary stereocenter via Kukhtin−Ramirez (K−R) adduct formation, with excellent diastereoselectivity and yields under metal-free ambient conditions. A few functional group transformations have also been performed successfully. Additionally, an asymmetric catalytic attempt using (R)-(+)-H8-BINOL has delivered good enantioselectivity.

P(NMe2)3-Mediated Regioselective N-Alkylation of 2-Pyridones via Direct Deoxygenation of α-Keto Esters

“…Nucleophilic displacement may subsequently give functionalized compounds. In this vein, X–H insertion reactions, difunctionalization, cyclopropanation, (1+4) annulation reactions, etc., have been frequently exploited.…”

Sequential In Situ-Formed Kukhtin–Ramirez Adduct and P(NMe2)3-Catalyzed O-Phosphination of α-Dicarbonyls with P(O)–H

“…have been developed as well, indicating the potential value of K–R intermediates in innovative applications. As is well-known, the in situ -formed K–R adducts presumably act as the active intermediates, which usually participate in the following reactions as nucleophilies. − On the other hand, K–R adducts could also be regarded as bases, which are rarely applied as in situ -formed basic catalysts. In this contribution, O -phosphination of α-dicarbonyls via the sequential in situ formation of the K–R adduct and a P­(NMe 2 ) 3 -catalyzed process has been exploited for the construction of α-phosphoryloxy carbonyls with H-phosphine oxides and α-dicarbonyls (Scheme d).…”

“…Remarkable efforts have been engaged in developing potential applications of K–R adducts in organic synthesis, especially by Radosevich . In addition, deoxygenative difunctionalization, cyclopropanation, and (1 + 4) annulation reactions, etc . have been developed as well, indicating the potential value of K–R intermediates in innovative applications.…”

Pd-Catalyzed Chemodivergent Synthesis of 1-Indanones via Diethyl Zinc-Mediated Precise Switching of Umpolung Reactivity

“…NHC organocatalysis is the most commonly used tool for umpolung chemistry, although other organocatalytic modes, metal catalysis, and photocatalysis are also employed. Alongside these, the stoichiometric use of organophosphine and organometallic reagents has further enriched this chemistry. In this context, depending on the additive present in the reaction medium, organometallic reagents generally react with the carbonyl functionality in either a 1,2 or 1,4 fashion .…”