Base-Catalyzed [1,n]-Proton Shifts in Conjugated Polyenyl Alcohols and Ethers

Abstract

The isomerization of dienyl alcohols and polyenyl alkyl ethers catalyzed by TBD (1,5,7triazabicyclo[4.4.0]dec-5-ene) under metal-free conditions is presented. Two reaction pathways have been observed. For dienyl alcohols, the reaction proceeds by a [1,3]-proton shift to give γ,δ-unsaturated ketones exclusively. On the other hand, the reaction with polyenyl alkyl ethers gives the corresponding conjugated vinyl ethers in good yields (up to 85%), with regioselectivities up to >20:1. Experimental and computational investigations suggest that the mechanism proceeds through consecutive "chain-walking" proton shifts ("base walk") mediated by TBD.

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

“… 1 Thus, when a catalyst promotes this process, the reaction must proceed in a stepwise manner via one or more intermediates. 2 A relevant example of this class of reaction is the isomerization of allylic alcohols into carbonyl compounds, a synthetic transformation in organic chemistry. 3 In recent decades, significant work has been put into the development of methods for performing this isomerization efficiently, 4 − 6 in some instances even under mild reaction conditions, and with a large substrate scope.…”

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

“…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).…”

“…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.…”

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.…”