Brønsted Acid-Catalysed Dehydrative Substitution Reactions of Alcohols

Abstract

The direct, catalytic dehydrative substitution of alcohols is a challenging, yet highly desirable process in the development of more sustainable approaches to organic chemistry. This review outlines recent advances in Brønsted acid-catalysed dehydrative substitution reactions for C-C, C-O, C-N and C-S bond formation. The wide range of processes that are now accessible using simple alcohols as the formal electrophile are highlighted, while current limitations and therefore possible future directions for research are also discussed.

Keywords: Brønsted acid; alcohols; dehydrative substitution; homogeneous catalysis; sustainable synthesis.

Scheme 1

General mechanisms for catalytic dehydrative substitution.

Scheme 2

Friedel–Crafts alkylation avoiding isomerisation.

Scheme 3

Friedel–Crafts alkylation using electron‐deficient benzylic alcohols.

Scheme 4

Reactions of α‐trifluoromethyl propargylic alcohols with arenes.

Scheme 5

Friedel–Crafts alkylation using potassium bifulfate.

Scheme 6

a) Boronic acid‐catalysed Friedel–Crafts alkylation using electron‐deficient alcohols. b) Proposed active catalyst formed in situ.

Scheme 7

a) Dehydrative homocoupling of benzylic alcohols. b) Friedel–Crafts alkylation using p‐TsOH.

Scheme 8

a) Phosphoric acid‐catalysed generation and reaction of oQMs. b) BINOL‐based chiral phosphoric acid catalysts.

Scheme 9

Aryl acetaldehyde addition to in situ generated oQMs.

Scheme 10

Dehydrative cyclisation of β‐keto acids with oQMs.

Scheme 11

Cooperative phosphoric acid and rhodium catalysed annulation to form substituted chromans.

Scheme 12

Palladium Brønsted acid‐catalysed annulation of oQMs and β‐keto esters.

Scheme 13

a) Reaction of α‐diazoketones with oQMs. b) Proposed spirocyclic phenonium ion intermediate.

Scheme 14

Enantioselective Friedel–Crafts alkylation of indole with oQMs.

Scheme 15

Enantioselective hetero‐Diels‐Alder reaction of styrenes with oQMs.

Scheme 16

Enantioselective cycloaddition of 2‐vinylindoles with oQMs.

Scheme 17

Enantioselective dehydrative [3+2] cycloaddition of 2‐vinylindoles with pyrrole methides.

Scheme 18

Triflic acid‐catalysed alkylation of 2‐methylquinoline.

Scheme 19

Enantioselective enolate addition to form 3‐indolyloxindole derivatives.

Scheme 20

Imidodiphosphoric acid‐catalysed addition of 3‐vinylindoles into 3‐indolylmethanols.

Scheme 21

Enantioselective 1,4‐addition of indole to 7‐indolyl methide precursor.

Scheme 22

a) Enantioselective formal [3+2] cycloadditions of enecarbamates with 3‐indolylmethanols. b) Formal [4+3] cycloadditions using dienecarbamates.

Scheme 23

Enantioselective [4+3] annulation of 2‐indolylmethanols with oQMs.

Scheme 24

Enantioselective [3+2] cycloaddition of 3‐hydroxy‐3‐indolyloxindoles with 2‐vinylindoles.

Scheme 25

a) Atroposelective addition of 2‐naphthol to vinyl iminium. b) Enantioselective synthesis of substituted 3,3′‐bisindoles.

Scheme 26

Triflamide‐catalysed addition of vinyl azides to 3‐hydroxy‐3‐indolyloxindoles.

Scheme 27

Enantioselective Friedel–Crafts alkylation of indoles with 3‐hydroxy‐3‐indolyloxindoles.

Scheme 28

BCF‐catalysed dehydrative intramolecular etherification.

Scheme 29

Catalytic intermolecular etherification of propargylic alcohols.

Scheme 30

a) Arylboronic acid‐catalysed dehydrative intermolecular etherification. b) Catalytic intramolecular etherification. c) Proposed active Brønsted acid catalyst formed in situ.

Scheme 31

Phosphoric acid‐catalysed enantioselective intermolecular etherification using oQMs.

Scheme 32

Phosphinic acid‐catalysed intramolecular etherification with chirality transfer.

Scheme 33

a) Enantioconvergent intramolecular Nicholas reaction of propargylic alcohols. b) Interconversion of intermediate planar‐chiral dicobalt complexes.

Scheme 34

BCF⋅H₂O catalysed azidation of tertiary alcohols.

Scheme 35

Diastereoselective [4+3] cycloaddition of oQMs with cyclic azomethine imines.

Scheme 36

Enantioselective intramolecular amination of allylic alcohols.

Scheme 37

Enantioconvergent intermolecular Nicholas reaction for thioetherification of propargylic alcohols.

Scheme 38

Catalytic reduction of 3‐indolylmethanols to form tertiary carbon stereocentres.