Desymmetrization of Prochiral Cyclobutanones via Nitrogen Insertion: A Concise Route to Chiral γ‐Lactams

Abstract

Supporting information for this article is given via a link at the end of the document.

Catalytic, asymmetric azidations at carbonyls: achiral and meso-anhydride desymmetrisation affords enantioenriched γ-lactams

“…TLC (95 : 5 CH 2 Cl 2 /MeOH): R f = 0.8. [ α ] 22 D = −0.81 ( c = 0.16, CHCl 3 ), (lit., 51 [ α ] 20 D = −2.42 ( c = 1.00, CHCl 3 ) for 99% ee). CSP-SFC analysis (see ESI†): R T : 1.88 min (minor enantiomer) and 2.00 min (major enantiomer).…”

Copper‐Nitrene‐Catalyzed Desymmetric Oxaziridination/1,2‐Alkyl Rearrangement of 1,3‐Diketones toward Bicyclic Lactams

“…However, the development of chemical transformations based on chiral copper–nitrene has mainly focused on the aziridination of C=C bonds to generate synthetically important aziridines [7] (Scheme 1 a). To further explore other novel transformations involving chiral copper‐nitrene species, we speculated that a polarized C=O bond could react with in situ generated copper‐nitrene and the resulting highly active intermediate oxaziridine [8] could subsequently rearrange to produce a synthetically challenging chiral lactam [4, 9] (Scheme 1 b). Such an asymmetric transformation could efficiently address the intrinsic challenges of the classic intramolecular Schmidt reaction, [10] including the use of azides with low nucleophilicity as a substrate, the general requirement for stoichiometric amounts of a strong Lewis or Brønsted acid to activate the carbonyl group of the other reactant, the relatively strong Lewis basic nature of the resulting lactam, and the lack of the corresponding catalytic asymmetric fashion.…”

Dynamic kinetic resolution of transient hemiketals: a strategy for the desymmetrisation of prochiral oxetanols

“…To address this limitation, we hypothesized that when adequately activated a transient hemiacetal would be able to undergo ring-opening at a strained heterocyclic core. Based on our laboratory's interest in desymmetrisation of prochiral four-membered rings, 7 we considered 3-oxetanols as promising candidates to test this hypothesis ( Scheme 1 , bottom). Here, the preformed hemiacetal attacks the oxetane ring to form a dioxolane, which is energetically favourable due to the ∼20 kcal mol −1 of strain release, and opens the possibility to forge two new stereogenic centres along the way.…”