Cascade‐ and Orthoamide‐Type Overman Rearrangements of Allylic Vicinal Diols

Abstract

This article describes the details of two new types of Overman rearrangement from allylic vicinal diols. Starting from identical diols, both bis(imidate)s and cyclic orthoamides were selectively synthesized by simply changing the reaction conditions. Whilst exposure of the bis(imidate)s to thermal conditions initiated the double Overman rearrangement to introduce two identical nitrogen groups in a single operation (the cascade-type Overman rearrangement), the reaction of cyclic orthoamides resulted in a single rearrangement (the orthoamide-type Overman rearrangement). The newly generated allylic alcohols from the orthoamide-type reaction can potentially undergo a variety of further transformations. For instance, we demonstrated an Overman/Claisen sequence in one pot. The most conspicuous feature of this method is that it offers precise control over the number of Overman rearrangements from the same allylic vicinal diols. This method also excludes the tedious protecting-group manipulations of the homoallylic alcohols, which are necessary in conventional Overman rearrangements. All of the performed rearrangements proceeded in a completely diastereoselective fashion through a chair-like transition state.

Enantioselective Total Synthesis of (+)‐Neostenine

“…Over the last decade, our research group has been exploring sequential [3,3]‐sigmatropic rearrangements of enantiopure allylic 1,2‐diols, which are derived from easily available naturally occurring polyols, such as monosaccharides . For example, the sequential Overman/Claisen rearrangement is depicted in Scheme b . Allylic 1,2‐diol 3 was converted to cyclic orthoamide 4 , which was in equilibrium at elevated temperature between trichloroimidates 5 and 6 .…”

“…Cyclic orthoamide 11 was smoothly formed upon treatment of allylic 1,2‐diol 19 with CCl 3 CN, DBU, and ZnCl 2 at 0 °C (Scheme ). Addition of a catalytic amount of ZnCl 2 was essential to suppress the basicity of DBU, resulting in the selective formation of cyclic orthoamides . Without the addition of ZnCl 2 , two equivalents of CCl 3 CN were installed to allylic 1,2‐diol 19 to give the bisimidate as a byproduct.…”

Crystal structure of (–)-methyl (R,E)-4-[(2R,4R)-2-amino-2-trichloromethyl-1,3-dioxolan-4-yl]-4-hydroxy-2-methylbut-2-enoate

“…Cyclic compounds often play a significant role, not only in controlling stereochemistry due to their conformational rigidity, but also as protecting groups in organic synthesis. On the basis of this concept, we have explored the utilization of cyclic orthoamides, prepared from allylic diol and triol with known conditions (Overman, 1974;1976), and have developed a new strategy for the total synthesis of a certain natural product (Nakayama, et al, 2013). The title compound is a structural isomer of a recently reported compound (Oishi et al, 2016).…”

Crystal structure of (+)-methyl (E)-3-[(2S,4S,5R)-2-amino-5-hydroxymethyl-2-trichloromethyl-1,3-dioxolan-4-yl]-2-methylprop-2-enoate

“…In the case of a diol, a cyclic orthoamide (2amino-2-trichloromethyl-1,3-dioxolane) may be afforded by controlling the reaction conditions though bis-imidates are usually produced. We have explored the rearrangement of the cyclic orthoamide prepared from a contiguous diol or triol, and have developed a novel strategy for the total synthesis of certain natural products (Nakayama et al, 2013). As part of our ongoing studies in this area, we now describe the synthesis and structure of the title compound.…”