Enantioselective Synthesis of Cyclopropanone Equivalents and Application to the Formation of Chiral β‐Lactams

Abstract

Cyclopropanone derivatives have long been considered unsustainable synthetic intermediates because of their extreme strain and kinetic instability.R eported here is the enantioselective synthesis of 1-sulfonylcyclopropanols,a ss table yet powerful equivalents of the corresponding cyclopropanone derivatives,bya-hydroxylation of sulfonylcyclopropanes using ab is(silyl) peroxide as the electrophilic oxygen source. This work constitutes the first general approach to enantioenriched cyclopropanone derivatives.B oth the electronic and steric nature of the sulfonyl moiety,w hich serves as ab aselabile protecting group and confers crystallinity to these cyclopropanone precursors,w ere found to have ac rucial impact on the rate of equilibration to the corresponding cyclopropanone.T he utility of these cyclopropanone surrogates is demonstrated in amild and stereospecific formal [3+ +1] cycloaddition with simple hydroxylamines,l eading to the efficient formation of chiral b-lactam derivatives.

N-Benzylhydroxylamine as a novel synthetic block in “C1N1” embedding reaction via α-C(sp3)–H activation strategy

“…1 The traditional reaction mode of N -benzylhydroxylamine is to serve as an “N1 source” in the synthesis of amine, ketonitrone and β-lactam derivatives (Scheme 1A-a). 2–4 In addition, only one example has been reported using N -benzylhydroxylamine as an “O1 source” for the construction of branched hydroxylamines (Scheme 1A-b). 5 Notably, the most prominent application of N -benzylhydroxylamine is as an “N1O1 synthon” for the direct synthesis of heterocycles.…”