Carbamoyl Radical‐Mediated Synthesis and Semipinacol Rearrangement of β‐Lactam Diols

Abstract

In an approach to the biologically important 6-azabicyclo[3.2.1]octane ring system, the scope of the tandem 4-exo-trig carbamoyl radical cyclization—dithiocarbamate group transfer reaction to ring-fused β-lactams is evaluated. β-Lactams fused to five-, six-, and seven-membered rings are prepared in good to excellent yield, and with moderate to complete control at the newly formed dithiocarbamate stereocentre. No cyclization is observed with an additional methyl substituent on the terminus of the double bond. Elimination of the dithiocarbamate group gives α,β- or β,γ-unsaturated lactams depending on both the methodology employed (base-mediated or thermal) and the nature of the carbocycle fused to the β-lactam. Fused β-lactam diols, obtained from catalytic OsO4-mediated dihydroxylation of α,β-unsaturated β-lactams, undergo semipinacol rearrangement via the corresponding cyclic sulfite or phosphorane to give keto-bridged bicyclic amides by exclusive N-acyl group migration. A monocyclic β-lactam diol undergoes Appel reaction at a primary alcohol in preference to semipinacol rearrangement. Preliminary investigations into the chemo- and stereoselective manipulation of the two carbonyl groups present in a representative 7,8-dioxo-6-azabicyclo[3.2.1]octane rearrangement product are also reported.

Diverse N‐Heterocyclic Ring Systems via Aza‐Heck Cyclizations of N‐(Pentafluorobenzoyloxy)sulfonamides

“…[22] Alternatively,c yclization of 7p generated regioisomeric 6azabicyclo[3.2.1]octene scaffold 8p in 76 %y ield. [23] Thes tructures of 8oand 8pwere confirmed by X-ray diffraction. [15] Preliminary studies show that the chemistry will be of utility in other contexts.A ll aza-Heck processes described so far involve 5exo cyclization;h owever,e ven at the present level of development, 6exo cyclization is possible (Scheme 4A).…”

Diverse N‐Heterocyclic Ring Systems via Aza‐Heck Cyclizations of N‐(Pentafluorobenzoyloxy)sulfonamides

“…For example, cyclization of 7 o , which involves a cycloheptene constructed by RCM, provided tropane 8 o in 60 % yield; this is the core structure of multiple natural products including cocaine . Alternatively, cyclization of 7 p generated regioisomeric 6‐azabicyclo[3.2.1]octene scaffold 8 p in 76 % yield . The structures of 8 o and 8 p were confirmed by X‐ray diffraction…”

Conformationally constrained fused bicyclic iminosugars: synthetic challenges and opportunities

“…100 In the course of their work towards the 6-azabicyclo[3.2.1]octane ring system, Grainger et al synthesized the bicyclic β-lactam diols 210 and 211 as well as triol 212 (Scheme 33). 103 Starting from compound 205, carbamoyl diethyldithiocarbamate 206 was readily prepared in two steps. The bicyclic skeleton was then formed in 84% yield by way of photo-induced 4-exo-trig radical cyclisation, with the dithiocarbamate moiety being transferred to the less hindered face of the resulting β-lactam 207 -obtained as the sole isolated product.…”