Stereospecific Isomerization of Allylic Halides via Ion Pairs with Induced Noncovalent Chirality

Abstract

A regioselective protocol for the synthesis of substituted allylic chlorides, bromides, and fluorides has been established. Remarkably, the method can be applied to the enantioselective synthesis of challenging chiral allylic chlorides. When the allylic halides are treated with the base triazabicyclodecene as the catalyst, a [1,3]-proton shift takes place, giving the corresponding vinyl halides in excellent yields with excellent Z : E ratios. Furthermore, the [1,3]-proton shift takes place with an outstanding level of chirality transfer from chiral allylic alcohols (≤98%) to give chiral trifluoromethylated vinyl chlorides.

Organic Superbases in Recent Synthetic Methodology Research

“…Similar comparisons were shown by Hoveyda in 2013 while optimizing the DBU‐catalyzed stereospecific isomerization of skipped 1,4‐enynes into chiral allene derivatives [22] . In 2020, Martín‐Matute extended this approach to the isomerization of related allyl chloride substrates, with a stereospecific example shown in Figure 2 b [23] …”

Synthesis of alpha,gamma-Chiral Trifluoromethylated Amines through the Stereospecific Isomerization of alpha-Chiral Allylic Amines

“…16,17,[20][21][22][23] Our group has contributed to this field with the stereospecific isomerization of -trifluoromethylated allylic alcohols, ethers, and halides mediated by catalytic amounts of the base 1,5,7triazabicyclo[4.4.0]dec-5-ene (TBD; Figure 2c). [20][21][22] Chirality is transferred from C to C in a stepwise manner, through the formation of a tight-ion-pair intermediate with induced noncovalent chirality (Figure 2c). When it comes to the basemediated isomerization of allylic amines yielding enamines, only one protocol has been reported to the best of our knowledge, which in this example is non-stereospecific.…”

“…12 An alternative method for the synthesis of carbonyl compounds with remote stereogenic centers is the stereospecific isomerization of -chiral allylic alcohols, which are easily accessible -chiral starting materials. 1,3,[13][14][15] These isomerization reactions can be mediated by achiral metal catalysts 16,17 or by achiral bases, [18][19][20][21][22][23] and take place through [1,3]-hydrogen shifts. The reaction takes place by a stepwise mechanism, so stereospecific examples are scarce.…”

“…The reaction takes place by a stepwise mechanism, so stereospecific examples are scarce. 16,17,[20][21][22][23] Our group has contributed to this field with the stereospecific isomerization of -trifluoromethylated allylic alcohols, ethers, and halides mediated by catalytic amounts of the base 1,5,7triazabicyclo[4.4.0]dec-5-ene (TBD; Figure 2c). [20][21][22] Chirality is transferred from C to C in a stepwise manner, through the formation of a tight-ion-pair intermediate with induced noncovalent chirality (Figure 2c).…”

Asymmetric allylic substitution–isomerization to axially chiral enamides via hydrogen-bonding assisted central-to-axial chirality transfer

“…With the development of the area, organic molecule catalysis has enabled efficient enantioselective [1,3]-allylic rearrangements since 2010. [4][5][6][7][8][9][10][11][12][13] In this case, [1,3]-H (proton) transfer would occur in the presence of an organic base catalyst. Very recently, the detailed mechanistic studies of stereospecic [1,3]allylic rearrangements showing chirality transfer were reported by Paton and co-workers.…”