Evolution, Development and Personal Experience in Studies of the Allyl Cyanate-to-Isocyanate Rearrangement

Abstract

Evolution and development of the synthesis and rearrangement of allyl cyanate is described. Allyl cyanate-to-isocyanate rearrangement is a concerted [3.3]-sigmatropic process involving highly selective [1,3]-chirality transfer to the newly formed asymmetric center bearing nitrogen. The usefulness of this rearrangement is manifested by the synthesis of natural products containing nitrogen-substituted quaternary carbon atoms. 1 Background 2 Evolution of the Allyl Cyanate-to-Isocyanate Rearrangement. A Personal History 3 The Stereochemistry and Mechanism of the Allyl Cyanateto-Isocyanate Rearrangement 4 Synthesis of Natural Products Containing Nitrogen-Substituted Quaternary Carbon Centers 5 Coda

Asymmetric hydrogenation of exocyclic γ,δ-unsaturated β-ketoesters to functionalized chiral allylic alcohols via dynamic kinetic resolution

“…The hydrogenation was completed within 8 h under 30 atm H 2 pressure and it afforded (−)- 8ag in 97% yield with 98% ee and 97 : 3 cis -selectivity. Carbamoylation of (−)- 8ag with trichloroacetyl isocyanate followed by dehydration with trifluoroacetic anhydride (TFAA) in the presence of NEt 3 yielded an allyl isocyanate intermediate 14 , which was then converted to allylic amine (+)- 15 in 88% yield (2 steps) via an Ichikawa rearrangement 20 and trapping with MeOH promoted by Bu 3 SnOMe according to Stecko's procedure. 21 Hydrogenation of allylic amine (+)- 15 on Pd/C afforded N -methoxycarbonyl δ-amino acid ester (−)- 16 in 98% yield with 6 : 1 diastereoselectivity.…”

Synthesis of Glycocinnasperimicin D

“…Selectivity [b] (dr, 14/21) À40 8C generated the allyl cyanate 13, which spontaneously underwent [3.3] sigmatropic rearrangement to afford allyl isocyanate 12. [18] Due to the pronounced lability of isocyanates toward hydrolysis, transformation of 12 was carried out without using an aqueous workup; the reaction mixture was treated with a large excess of 2,2,2-trichloroethanol (12 equiv). Workup and purification then furnihsed the Troc-carbamate 23 in 76 % overall yield from allyl alcohol 14.…”

The Allyl Cyanate/Isocyanate Rearrangement: An Efficient Tool for the Stereocontrolled Formation of Allylic C–N Bonds

“…In this context, the allyl cyanate/isocyanate transposition has now become an attractive alternative to the Overman rearrangement of allylic trichloroacetimidates, due to the mild reaction conditions and the high degree of stereocontrol (Scheme ). Initially reported by Holm and Christophersen in 1970, and later by Overman and Kakimoto, this reaction only emerged as a powerful synthetic method twenty years later, with the discovery of an efficient route to allyl cyanates by dehydration of carbamates . Since this seminal work by Ichikawa, the utility of this allylamine synthesis has continued to grow rapidly, thereby justifying a review of the most recent developments in this field.…”