Synthesis of Chiral Tetrasubstituted Azetidines from Donor–Acceptor Azetines via Asymmetric Copper(I)‐Catalyzed Imido‐Ylide [3+1]‐Cycloaddition with Metallo‐Enolcarbenes

Abstract

The all-cis stereoisomers of tetrasubstituted azetidine-2-carboxylic acids and derivatives that possess three chiral centers have been prepared in high yield and stereocontrol from silyl-protected Z-g-substituted enoldiazoacetates and imido-sulfur ylides by asymmetric [3+ +1]-cycloaddition using chiral sabox copper(I) catalysis followed by Pd/C catalytic hydrogenation. Hydrogenation of the chiral p-methoxybenzyl azetine-2-carboxylates occurs with both hydrogen addition to the C = Cbond and hydrogenolysis of the ester.

Copper(I)‐Catalyzed Highly Enantioselective [3+3]‐Cycloaddition of β‐Aryl/Alkyl Vinyl Diazoacetates with Nitrones

“…Recent progress with enantioselective cycloaddition reactions of enoldiazo compounds [17–19] prompted us to examine enantiocontrol in the [3+3] cycloaddition of β‐aryl/alkyl vinyldiazoacetates with nitrones catalyzed by copper(I) complexes with chiral ligands. Various Box ligands coordinated with Cu(MeCN) 4 BF 4 were evaluated, and the results are summarized in Table 2.…”

Mukaiyama Award: M. D. Burke und S. Matsunaga / Ryoji Noyori Prize and Paracelsus Prize: S. E. Denmark / Henry J. Albert Award: M. P. Doyle / ORCS Awards: P. Chirik und J. J. Spivey / FNP Award: M. Drąg

“…They develop chiral ligands for dirhodium(II) carboxylate and copper(I) catalysts. Most recent contributions have been to catalytic cycloaddition of enoldiazo compounds, as exemplified by a Communication in Angewandte Chemie on a copper‐catalyzed synthesis of chiral tetrasubstituted azetidines, and to selective free radical addition reactions.…”

Mukaiyama‐Preis: M. D. Burke und S. Matsunaga / Ryoji‐Noyori‐Preis und Paracelsus‐Preis: S. E. Denmark / Henry J. Albert‐Preis: M. P. Doyle / ORCS‐Preise: P. Chirik und J. J. Spivey / FNP‐Preis: M. Drąg

“…Sie entwickeln chirale Liganden für Dirhodium(II)‐Carboxylat‐ und Kupfer(I)‐Katalysatoren. In jüngeren Arbeiten befassten sie sich meist mit katalytischen Cycloadditionen von Enoldiazoverbindungen, wie in einer Angewandte‐Chemie ‐Zuschrift über eine kupferkatalysierte Synthese chiraler tetrasubstituierter Azetidine, und mit selektiven radikalischen Additionen.…”