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. 2019 Jul 1;48(13):3436-3453.
doi: 10.1039/c9cs00218a.

Late-stage functionalization of BN-heterocycles

Cameron R McConnell  1 , Shih-Yuan Liu
Affiliations

Late-stage functionalization of BN-heterocycles

Cameron R McConnell et al. Chem Soc Rev. .

Abstract

BN/CC isosterism has emerged as a viable strategy to expand the chemical space of organic molecules. In particular, the application of BN/CC isosterism to arenes has received significant attention due to the vast available chemical space provided by aromatic hydrocarbons. The synthetic efforts directed at assembling novel aromatic BN heterocycles have resulted in the discovery of new properties and functions in a variety of fields including biomedical research, medicinal chemistry, materials science, catalysis, and organic synthesis. This tutorial review specifically covers recent advances in synthetic technologies that functionalize assembled boron-nitrogen (BN) heterocycles and highlights their distinct reactivity and selectivity in comparison to their carbonaceous counterparts. It is intended to serve as a state-of-the-art compendium for readers who are interested in the reaction chemistry of BN heterocycles.

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Conflict of interest statement

Conflicts of interest

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1
Halogenation of various 1,2-azaborines through EAS.
Scheme 2
Scheme 2
Acylation of 1,2-azaborines at C5 position.
Scheme 3
Scheme 3
Other C5 functionalization methods by Ashe and Fang.
Scheme 4
Scheme 4
Substrate table for the C–H borylation of 1,2-azaborines.
Scheme 5
Scheme 5
(a) Suzuki cross-coupling of borylated 1,2-azaborines. (b) Polymerization of C6-borylated, C3-brominated monomer via Suzuki cross-coupling.
Scheme 6
Scheme 6
Suzuki cross-coupling of B-H and B-O-nBu substituted 1,2-azaborines.
Scheme 7
Scheme 7
Negishi cross-coupling of C3–Br 1,2-azaborine 4.
Scheme 8
Scheme 8
(a) Nucleophilic substitution reaction of 1,2-azaborine. (b) In situ generation of N-H-B-Cl-1,2-azaborine 14n followed by nucleophilic substitution at boron.
Scheme 9
Scheme 9
(a) Nucleophilic substitution of N-alkyl-B-Cl 1,2-azaborines. (b) Substitution with in situ generated nucleophiles. (c) Synthesis of azaborine-containing triarylphosphine ligands.
Scheme 10
Scheme 10
Preparation of azaborine cations from B-OTf-substituted 1,2-azaborine 25.
Scheme 11
Scheme 11
Nucleophilic substitution of N-TBS-B-Cl 1,2-azaborine.
Scheme 12
Scheme 12
Nucleophilic addition to sterically hindered C3-substituted N-TBS-B-Cl-1,2-azaborines.
Scheme 13
Scheme 13
Nucleophilic substitutions at C3 position of azaborine.
Scheme 14
Scheme 14
(a) Generation of amide 30a and N-substitution with electrophiles. (b) Boc protection of the N-position of the 1,2-azaborine.
Scheme 15
Scheme 15
Reaction between 1,2-azaborine amide 30b and epoxides.
Scheme 16
Scheme 16
Removal of the N-TBS protecting group of 1,2-azaborine.
Scheme 17
Scheme 17
Rh-Catalyzed arylation of B-Cl 1,2-azaborines.
Scheme 18
Scheme 18
Rh-catalyzed B–H activation of 1,2-azaborines.
Scheme 19
Scheme 19
Cu-Catalyzed B–R oxidation of 1,2-azaborines.
Scheme 20
Scheme 20
Intramolecular Cu-catalyzed B-R activation and oxidation of 1,2-azaborines to form BN-dihydrobezofuran isosteres.
Scheme 21
Scheme 21
Free-radical polymerization of B-vinyl-1,2-azaborines.
Scheme 22
Scheme 22
Hydrogenation of C6-vinyl azaborine.
Scheme 23
Scheme 23
Diels–Alder reaction of 1,2-disubstituted-1,2-azaborines.
Scheme 24
Scheme 24
Diels–Alder reaction of azaborine 27a with activated dienophiles.
Scheme 25
Scheme 25
(a) Bromination of 1,2-BN-naphthalene. (b) Dibromination of 1,2-BN-naphthalene. (c) Bromination of C3-substituted 1,2-BN-naphthalene.
Scheme 26
Scheme 26
Mono and dihalogenation of 9,10-BN-naphthalene.
Scheme 27
Scheme 27
Acylation of 9,10-BN-naphthalene.
Scheme 28
Scheme 28
(a) Acylation of BN-aryl ketone 54a. (b) BN-phenalenone 55 prepared via-acylation–cyclization procedure. (c) Nitration of BN-naphthalene 52.
Scheme 29
Scheme 29
(a) C1 acylation of 9,10-BN-naphthalene. (b) C2, C7 difunctionalization of 9,10-BN-naphthalene via activation with n-BuLi.
Scheme 30
Scheme 30
(a) Miyaura borylation of 3-bromo-1,2-BN-naphthalenes. (b) Conversion of 3-Bpin-1,2-BN-naphthalenes to corresponding BF3K salts.
Scheme 31
Scheme 31
(a) C–H borylation at C8 position of N-H-1,2-BN-naphthalene. (b) Bisborylation at C8 and C6 positions of 1,2-BN-naphthalene. (c) Mono-borylation at C7 and C6 positions of N-substituted 1,2-BN-naphthalene.
Scheme 32
Scheme 32
Suzuki cross-coupling of 3-bromo-1,2-BN-naphthalenes and (a) aryl BF3K reagents; (b) alkenyl BF3K reagents. (c) Kumada cross-coupling of 3-bromo-1,2-naphthalenes and aryl Grignard reagents.
Scheme 33
Scheme 33
(a) Reductive cross-coupling of 3-bromo-1,2-BN-naphthalenes and alkyl iodides. (b) Photoredox/nickel dual-catalytic functionalization of 3-bromo-1,2-BN-naphthalenes.
Scheme 34
Scheme 34
(a) Cross-coupling of C3-Bpin-1,2-BN-naphthalene. (b) Cross-coupling of C3-BF3K-1,2-BN-naphthalene.
Scheme 35
Scheme 35
Self-arylation of 1,2-BN-naphthalenes.
Scheme 36
Scheme 36
(a) Suzuki coupling at the C4 position of 1,2-BN-naphthalene; (b) C3 and C6 positions; (c) C6 position; (d) C8 position.
Scheme 37
Scheme 37
(a) Suzuki coupling of 9,10-BN-naphthalene; (b) Sonogashira coupling; (c) Heck reaction; (d) C–P coupling.
Scheme 38
Scheme 38
(a) Nucleophilic substitution at the boron position of 1,2-BN-naphthalene by Dewar. (b) Nucleophilic substitution at the boron position of 1,2-BN-naphthalene by Molander. (c) Nucleophilic substitution at the boron position of 2,1-BN-naphthalene by Cui.
Scheme 39
Scheme 39
Benzylic functionalizations of 1,2-BN-naphthalene.
Scheme 40
Scheme 40
Copolymerization of styrene and 1,2-BN-naphthalene 44d.
Scheme 41
Scheme 41
Electrophilic substitution at the nitrogen position of 1,2-BN-naphthalene.
Scheme 42
Scheme 42
EAS reactions of 9,10-BN-phenanthrene.
Scheme 43
Scheme 43
EAS reactions of 4a,10a-BN-phenanthrene.
Scheme 44
Scheme 44
(a) Bromination of 1,2-BN-anthracene. (b) Bromination of 9a,9-BN-anthracene.
Scheme 45
Scheme 45
Bromination of BN-tetraphene.
Scheme 46
Scheme 46
Cross-coupling reactions of brominated BN-phenanthrene 98b.
Scheme 47
Scheme 47
(a) Cross-coupling at C9 position of 1,2-BN-anthracene. (b) Cross-coupling at C10 position of 9a,9-BN-anthracene.
Scheme 48
Scheme 48
Cross-coupling of BN-tetraphene.
Scheme 49
Scheme 49
Nucleophilic substitution of 9,10-BN-phenanthrene 113.
Scheme 50
Scheme 50
Electrophilic substitution at N of 9,10-BN-phenanthrene.
Scheme 51
Scheme 51
Exchange reaction between B–Cl 113 and silylphosphines.
See this image and copyright information in PMC

References

    1. For an overview of BN/CC isosterism in aromatic compounds, see: Bosdet MJD and Piers WE, Can. J. Chem, 2009, 87, 8–29.
    1. For a history of azaborine chemistry, see: Campbell PG, Marwitz AJV and Liu S-Y, Angew. Chem., Int. Ed, 2012, 51, 6074–6092. - PMC - PubMed
    1. For recent developments in azaborine chemistry, see: Bélanger-Chabot G, Braunschweig H and Roy DK, Eur. J. Inorg. Chem, 2017, (38–39), 4353–4368.
    1. For a perspective on the applications of azaborines, see: Giustra ZX and Liu S-Y, J. Am. Chem. Soc, 2018, 140, 1184–1194. - PMC - PubMed
    1. Pan J, Kampf JW and Ashe AJ, Org. Lett, 2007, 9, 679–681. - PubMed