Total Syntheses of Vicinal Dichloride Monoterpenes Enabled by Aza-Belluš–Claisen Rearrangement

Abstract

Diastereoselective syntheses of syn- and anti-vicinal dihalides were achieved via an aza-Belluš–Claisen rearrangement, which involved the reaction of an α-chloro carboxylic acid chloride with halogen-substituted trans-allyl morpholines in the presence of Lewis acids. The developed method was used for the total synthesis of a group of monoterpene natural products bearing vicinal dichloride subunits.

Reshuffle Bonds by Ball Milling: A Mechanochemical Protocol for Charge-Accelerated Aza-Claisen Rearrangements

“…Despite their synthetic relevance as bond forming reactions, all of these original protocols have one disadvantage in common: a high energy demand [ 21 , 30 , 31 ]. Consequently, catalytic protocols that make use of transition metal complexes [ 55 , 56 , 57 , 58 , 59 , 60 , 61 ], Lewis or Brønsted acids [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ], or organocatalysts [ 75 , 76 , 77 , 78 , 79 , 80 ], were developed to shape the (energy) efficiency of the Claisen rearrangement. Along these lines, the ‘on-water’-effect was explored to reduce the reaction temperatures, too [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ].…”