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Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
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Stereospecific Nitrogen Insertion Using Amino Diphenylphosphinates: An Aza-Baeyer-Villiger Rearrangement.
Mike Ong1,2, Marlene Arnold2, Alexander W Walz2
1Organisch-Chemisches Institut, Westfälische Wilhelms-Universität, Corrensstraße 36, 48149 Münster, Germany.
Organic Letters
|August 17, 2022
Summary
Amino diphenylphosphinates enable mild cyclobutanone ring expansion to gamma-lactams. This novel reaction pathway, distinct from the Beckmann rearrangement, offers high selectivity and stereospecificity for late-stage synthesis.
Area of Science:
- Organic Chemistry
- Synthetic Methodology
- Reaction Mechanisms
Background:
- Cyclobutanones are versatile synthetic intermediates.
- Gamma-lactams are important structural motifs in pharmaceuticals.
- Existing methods for gamma-lactam synthesis often lack efficiency or selectivity.
Purpose of the Study:
- To develop a novel method for the synthesis of gamma-lactams from cyclobutanones.
- To investigate a reaction pathway distinct from the traditional Beckmann rearrangement.
- To achieve highly selective and stereospecific ring expansion.
Main Methods:
- Reaction of cyclobutanones with amino diphenylphosphinates under mild conditions.
- Mechanistic studies to elucidate the reaction pathway, including Criegee-like intermediates.
- Analysis of migrating group aptitude and reaction selectivity.
Main Results:
- Efficient ring expansion of cyclobutanones to gamma-lactams was achieved.
- A novel reaction mechanism involving a Criegee-like intermediate, preceding oxime formation, was identified.
- The reaction demonstrated high regioselectivity (>99:1 rr), stereospecificity (>99% enantiospecificity), and chemoselectivity (>99%).
Conclusions:
- A new synthetic route to gamma-lactams from cyclobutanones using amino diphenylphosphinates has been established.
- The reaction proceeds via a unique pathway, offering advantages over the conventional Beckmann rearrangement.
- This method is suitable for late-stage skeletal editing in complex molecule synthesis, as demonstrated by the synthesis of Rolipram.
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