Ireland-Claisen Rearrangement of 6-Methylene-1,4-oxazepan-2-ones

• Published in: European journal of organic chemistry Vol. 2015; no. 30; pp. 6701 - 6709
• Main Authors: Smits, Gints, Kinens, Artis, Zemribo, Ronalds
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.10.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Amino acids; Boron; Chemistry; Chemistry, Organic; Density functional calculations; Natural products; Physical Sciences; Science & Technology; Sigmatropic rearrangement; Transition states; Transition states; Boron; Natural products; SCOPE; AMINO-ACIDS; Amino acids; Density functional calculations; Sigmatropic rearrangement; STEREOSELECTIVE TOTAL-SYNTHESIS; CYCLIZATION
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201500918

The Ireland–Claisen rearrangement of 6‐methylene‐1,4‐oxazepan‐2‐one‐derived boron enolates leads to stereochemically defined, synthetically useful 4‐(E)‐ethylidene prolines. Detailed computational and experimental studies explain the stereochemical outcome of this transformation and suggest an unusual double‐chelated transition state that involves two boron atoms. The scope of the method is also explored. The Ireland–Claisen rearrangement of 6‐methylene‐1,4‐oxazepan‐2‐one‐derived boron enolates proceeds through an unusual double‐chelated transition state, and both experimental and DFT calculations fully support this hypothesis. The obtained 4‐(E)‐ethylidene prolines can be used in the total syntheses of a number of biologically important natural products; PMB = p‐methoxybenzyl, OTf = triflate.