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Review
. 2020 Oct 16;15(20):3135-3161.
doi: 10.1002/asia.202000730. Epub 2020 Sep 9.

Benzylic Methylene Functionalizations of Diarylmethanes

Upma Gulati  1 , Radhika Gandhi  1 , Joydev K Laha  1
Affiliations
Review

Benzylic Methylene Functionalizations of Diarylmethanes

Upma Gulati et al. Chem Asian J. .

Abstract

Diarylmethanes are cardinal scaffolds by virtue of their unique structural feature including the presence of a benzylic CH2 group that can be easily functionalized to generate a variety of fascinating molecules holding immense importance in pharmaceutical, agrochemical, and material sciences. While the originally developed protocols for benzylic C-H functionalization in diarylmethanes employing base-mediated and metal-catalyzed strategies are still actively used, they are joined by a new array of metal-free conditions, offering milder and benign conditions. With the recent surge of interest towards the synthesis of functionalized diarylmethanes, numerous choices are now available for a synthetic organic chemist to transform the benzylic C-H bond to C-C or C-X bond offering the synthesis of any molecule of choice. This review highlights benzylic methylene (CH2 ) functionalizations of diaryl/heteroarylmethanes utilizing various base-mediated, transition-metal-catalyzed, and transition-metal free approaches for the synthesis of structurally diverse important organic molecules, often with a high chemo-, regio- and enantio-selectivity. This review also attempts to provide analysis of the scope and limitations, mechanistic understanding, and sustainability of the transformations.

Keywords: Benzylic C−H functionalization; Diarylmethanes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representatives of biologically active diarylmethanes.
Scheme 1
Scheme 1
Approaches for functionalization of benzylic C−H bond.
Scheme 2
Scheme 2
Synthesis of triarylmethanes using LDA‐mediated conditions.
Scheme 3
Scheme 3
Base‐catalyzed regioselective and stereoselective substitution onto diarylmethane.
Scheme 4
Scheme 4
BuLi‐mediated asymmetric synthesis of α‐(Diarylmethyl) alkyl amines
Scheme 5
Scheme 5
HMPA promoted siladifluoromethylation of diarylmethanes with Ruppert‐Prakash reagent.
Scheme 6
Scheme 6
FeCl2‐mediated oxidative cross‐coupling reaction.
Scheme 7
Scheme 7
Iron‐catalyzed Heck‐type direct olefination.
Scheme 8
Scheme 8
Iron‐catalyzed cross‐coupling to form C(sp2)−C(sp3) bond.
Scheme 9
Scheme 9
Iron‐catalyzed amidation of benzylic sp3C−H bond for the synthesis of carboxamides and sulfonamides.
Scheme 10
Scheme 10
Iron‐catalyzed cross‐coupling of diarylmethanes and benzimidazoles.
Scheme 11
Scheme 11
Iron‐catalyzed hetero‐cross dehydrogenative coupling.
Scheme 12
Scheme 12
Iron promoted chlorobenzylation through benzylic C(sp3)−H functionalization.
Scheme 13
Scheme 13
Copper‐catalyzed C−C bond formation via in‐situ substitution.
Scheme 14
Scheme 14
Functionalization of diphenylmethanes via a cross‐dehydrogenative Sonogashira coupling.
Scheme 15
Scheme 15
Copper‐catalyzed benzylic C−H oxidation.
Scheme 16
Scheme 16
Copper‐catalyzed sulfamidation through benzylic C−H functionalization.
Scheme 17
Scheme 17
Use of N‐Hydroxyphthalimide for selective C−H functionalization.
Scheme 18
Scheme 18
Copper‐catalyzed enantioselective C−H functionalization.
Scheme 19
Scheme 19
Copper‐catalyzed benzylic C−H oxygenation.
Scheme 20
Scheme 20
Copper‐catalyzed direct transformation of diarylmethanes into tetrazoles.
Scheme 21
Scheme 21
Copper‐assisted photoredox‐catalyzed azidation of benzylic C−H for C−N bond formation.
Scheme 22
Scheme 22
Copper‐catalyzed azidation of benzylic C−H bonds
Scheme 23
Scheme 23
Copper‐catalyzed Benzylic C(sp3)−H amination.
Scheme 24
Scheme 24
Benzylic C(sp3)−H amination via stable catalyst‐ligand‐oxidant system.
Scheme 25
Scheme 25
Copper‐catalyzed enantioselective arylation of benzylic C−H bonds.
Scheme 26
Scheme 26
Copper‐catalyzed C−H functionalization viaC−H fluorination.
Scheme 27
Scheme 27
Cobalt‐ catalyzed nitrene insertion to benzylic C−H bond.
Scheme 28
Scheme 28
Dehydrogenative amination of benzylic C−H bond.
Scheme 29
Scheme 29
Palladium‐catalyzed synthesis of triarylmethanes.
Scheme 30
Scheme 30
Palladium‐catalyzed enantioselective benzylic allylation.
Scheme 31
Scheme 31
Palladium‐catalyzed direct benzylation of azoles using benyl carbonates.
Scheme 32
Scheme 32
Palladium‐catalyzed synthesis of polyarylated methanes.
Scheme 33
Scheme 33
Palladium‐catalyzed allylation reactions of toluene derived pronucleophiles.
Scheme 34
Scheme 34
Palladium‐catalyzed deprotonative cross‐coupling reactions for intermolecular benzylic C−H arylation.
Scheme 35
Scheme 35
Palladium‐catalyzed benzylic allylation.
Scheme 36
Scheme 36
Pd/NiXantphos‐catalyzed synthesis of triaylmethanes and subsequent oxidation.
Scheme 37
Scheme 37
Palladium‐catalyzed synthesis of tri and tetraaryl/heteroarylmethanes.
Scheme 38
Scheme 38
Bismuth‐catalyzed benzylic oxidation.
Scheme 39
Scheme 39
Functionalization of diphenylmethanes with 1,3‐dicarbonyl compounds.
Scheme 40
Scheme 40
Rhodium‐catalyzed arylation of aryl/heteroaryl methane.
Scheme 41
Scheme 41
Rhodium‐catalyzed enantioselective functionalization of diarylmethane for the synthesis of chiral triarylmethane.
Scheme 42
Scheme 42
Nickel‐catalyzed benzylic C−H functionalization.
Scheme 43
Scheme 43
Nickel‐catalyzed benzylic allylation
Scheme 44
Scheme 44
C−N bond formation using manganese catalysis.
Scheme 45
Scheme 45
Synthesis of triarylmethanes using nickel and NHC catalyst system.
Scheme 46
Scheme 46
Photochemical metal‐free direct 4‐pyridination.
Scheme 47
Scheme 47
Photocatalytic benzylic C−H fluorination.
Scheme 48
Scheme 48
Visible‐light‐catalyzed direct benzylic C(sp3)−H amination.
Scheme 49
Scheme 49
Photocatalytic benzylic C(sp3)−H bond functionalization.
Scheme 50
Scheme 50
Aerobic oxygenation of benzylic C(sp3)−H bond.
Scheme 51
Scheme 51
Photocatalyzed synthesis of functionalized sulfoximines.
Scheme 52
Scheme 52
Photoredox/enzymatic catalysis for the enantioselective hydroxylation of benzylic C−H.
Scheme 53
Scheme 53
Metal‐free C−N bond formation via in‐situ halide substitution.
Scheme 54
Scheme 54
Oxidative C−N bond formation via iodine.
Scheme 55
Scheme 55
Benzylic oxidation of diarylmethanes using alkali metal bromide and oxidants.
Scheme 56
Scheme 56
Oxidative C−O coupling via DDQ.
Scheme 57
Scheme 57
TBHP/TBAI‐mediated C−O bond formation.
Scheme 58
Scheme 58
DDQ‐mediated functionalization of benzylic C−H bond.
Scheme 59
Scheme 59
Transition metal free oxidative C−N coupling.
Scheme 60
Scheme 60
Synthesis of diarylketones using DDQ.
Scheme 61
Scheme 61
Oxidant‐mediated C−N bond formation.
Scheme 62
Scheme 62
Cross‐dehydrogenative coupling of 1H‐1,2,4‐triazoles with methyl arenes.
Scheme 63
Scheme 63
TBHP‐mediated synthesis of diaryl/heteroarylmethanes
Scheme 64
Scheme 64
Ionic liquid‐catalyzed oxidative C−N bond formation.
Scheme 65
Scheme 65
N‐ hydroxyphthalimide‐mediated C−N bond formation.
Scheme 66
Scheme 66
NBS‐catalyzed synthesis of diarylketones.
Scheme 67
Scheme 67
Oxidative benzylic C−H functionalization.
Scheme 68
Scheme 68
Base‐mediated oxidative benzylic C−H functionalization.
Scheme 69
Scheme 69
Synthesis of functionalized diarylmethanes through potassium‐zincate complex catalysis.
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