Asymmetric Synthesis ofcis-3,4-Disubstituted β-Sultams

Abstract

A s y m m e t r i c S y n t h e s i s o f c i s -3 , 4 -D i s u b s t i t u t e d b -S u l t a m sAbstract: The asymmetric synthesis of cis-3,4-disubstituted b-sultams is reported. The protocol is based on the oxidation of 1,2-aminothiols with H 2 O 2 and ammonium heptamolybdate. The chlorination of the resulting b-amino sulfonic acids was achieved utilising a solution of phosgene in toluene. The b-aminosulfonyl chlorides obtained were cyclised to the title compounds under basic conditions without epimerisation (de, ee ≥96%) and good overall yields (17-59%). In addition, the N-Cbz-protection of b-sultams was easily accomplished.

[2 + 2] Annulation of Aldimines with Sulfonic Acids: A Novel One‐Pot cis‐Selective Route to β‐Sultams

“…The formation of β‐sultams 3 was entirely diastereoselective in favour of the cis isomer, which conforms with earlier observations of similar reactions 16b,21. The cis configuration of the substituted β‐sultams was proved by nuclear overhauser effect measurements of 3 (Figure 2) along with the J values between the protons at C‐3 and C‐4 ( J = 8.5–8.8 Hz), which favourably compare with those reported by Enders and Moll (8.4 Hz)6 and Zajac and Peters (7.3–9.1 Hz) 16b. However, cis ‐configured β‐lactams typically exhibit a lower value for the coupling constants (around 5 Hz).…”

“…The proton at C‐3 does not show any NOE with the protons of substituent at C‐4, and the proton at C‐4 shows no NOE with that of the substituent at C‐3. This conclusively demonstrates the cis stereochemistry of the synthesized β‐sultams 3 , which is also finally confirmed by comparison with authentic samples obtained by literature methods 6,16,20,22…”

“…The structure of the products was confirmed by their elemental and spectral analyses. In case of known compounds, the data compared favourably with those reported in the literature 6,16,20,22…”

“…From a chemical viewpoint, β‐sultams can act as peptidomimetics in sulfonyl transfer reactions and as potent sulfonating agents for a variety of nucleophiles6–8 to afford a wide range of important chemicals. Page et al have exhaustively studied the reactivity of β‐sultams with nucleophiles and found that it depends on the N ‐substituent 9.…”

“…The [2 + 2] cycloaddition reported for β‐sultam synthesis utilizes mainly sulfene intermediates with imines,10 mesyl chloride with chiral imines,11 or alkenes with N ‐sulfonylamines 12. The intramolecular cyclization strategy involves use of amino acids followed by introduction of the sulfur moiety,13 β‐amino sulfonic acids,6 heterocyclic sulfonates14 or β‐aminosulfonyl chlorides,15 for diastereo‐ and enantioselective synthesis of β‐sultams 6,8,16…”