Recent advances in Cu-catalyzed C(sp3)-Si and C(sp3)-B bond formation

Abstract

Numerous reactions generating C-Si and C-B bonds are in focus owing to the importance of incorporating silicon or boron into new or existing drugs, in addition to their use as building blocks in cross-coupling reactions en route to various targets of both natural and unnatural origins. In this review, recent protocols relying on copper-catalyzed sp³ carbon-silicon and carbon-boron bond-forming reactions are discussed.

Keywords: C–B bonds; C–Si bonds; copper catalysis; enantioselective reactions; sp3 carbon functionalization.

Scheme 1

Pharmaceuticals possessing a silicon or boron atom.

Scheme 2

The first Cu-catalyzed C(sp³)–Si bond formation.

Scheme 3

Conversion of benzylic phosphate 6 to the corresponding silane.

Scheme 4

Conversion of alkyl triflates to alkylsilanes.

Scheme 5

Conversion of secondary alkyl triflates to alkylsilanes.

Scheme 6

Conversion of alkyl iodides to alkylsilanes.

Scheme 7

Trapping of intermediate radical through cascade reaction.

Scheme 8

Radical pathway for conversion of alkyl iodides to alkylsilanes.

Scheme 9

Conversion of alkyl ester of N-hydroxyphthalimide to alkylsilanes.

Scheme 10

Conversion of gem-dibromides to bis-silylalkanes.

Scheme 11

Conversion of imines to α-silylated amines (A) and the reaction pathway (B).

Scheme 12

Conversion of N-tosylimines to α-silylated amines.

Scheme 13

Screening of diamine ligands.

Scheme 14

Conversion of N-tert-butylsulfonylimines to α-silylated amines.

Scheme 15

Conversion of aldimines to nonracemic α-silylated amines.

Scheme 16

Conversion of N-tosylimines to α-silylated amines.

Scheme 17

Reaction pathway [A] and conversion of aldehydes to α-silylated alcohols [B].

Scheme 18

Conversion of aldehydes to benzhydryl silyl ethers.

Scheme 19

Conversion of ketones to 1,2-diols (A) and conversion of imines to 1,2-amino alcohols (B).

Scheme 20

Ligand screening (A) and conversion of aldehydes to α-silylated alcohols (B).

Scheme 21

Conversion of aldehydes to α-silylated alcohols.

Scheme 22

1,4-Additions to α,β-unsaturated ketones.

Scheme 23

1,4-Additions to unsaturated ketones to give β-silylated derivatives.

Scheme 24

Additions onto α,β-unsaturated lactones to give β-silylated lactones.

Scheme 25

Conversion of α,β-unsaturated to β-silylated lactams.

Scheme 26

Conversion of N-arylacrylamides to silylated oxindoles.

Scheme 27

Conversion of α,β-unsaturated carbonyl compounds to silylated tert-butylperoxides.

Scheme 28

Catalytic cycle for Cu(I) catalyzed α,β-unsaturated compounds.

Scheme 29

Conversion of p-quinone methides to benzylic silanes.

Scheme 30

Conversion of α,β-unsaturated ketimines to regio- and stereocontrolled allylic silanes.

Scheme 31

Conversion of α,β-unsaturated ketimines to enantioenriched allylic silanes.

Scheme 32

Regioselective conversion of dienedioates to allylic silanes.

Scheme 33

Conversion of alkenyl-substituted azaarenes to β-silylated adducts.

Scheme 34

Conversion of conjugated benzoxazoles to enantioenriched β-silylated adducts.

Scheme 35

Conversion of α,β-unsaturated carbonyl indoles to α-silylated N-alkylated indoles.

Scheme 36

Conversion of β-amidoacrylates to α-aminosilanes.

Scheme 37

Conversion of α,β-unsaturated ketones to enantioenriched β-silylated ketones, nitriles, and nitro derivatives in water.

Scheme 38

Regio-divergent silacarboxylation of allenes.

Scheme 39

Silylation of diazocarbonyl compounds, (A) asymmetric and (B) racemic.

Scheme 40

Enantioselective hydrosilylation of alkenes.

Scheme 41

Conversion of 3-acylindoles to indolino-silanes.

Scheme 42

Proposed mechanism for the silylation of 3-acylindoles.

Scheme 43

Silyation of N-chlorosulfonamides.

Scheme 44

Conversion of acyl silanes to α-silyl alcohols.

Scheme 45

Conversion of N-tosylaziridines to β-silylated N-tosylamines.

Scheme 46

Conversion of N-tosylaziridines to silylated N-tosylamines.

Scheme 47

Conversion of 3,3-disubstituted cyclopropenes to silylated cyclopropanes.

Scheme 48

Conversion of conjugated enynes to 1,3-bis(silyl)propenes.

Scheme 49

Proposed sequence for the Cu-catalyzed borylation of substituted alkenes.

Scheme 50

Cu-catalyzed synthesis of nonracemic allylic boronates.

Scheme 51

Cu–NHC catalyzed synthesis of α-substituted allylboronates.

Scheme 52

Synthesis of α-chiral (γ-alkoxyallyl)boronates.

Scheme 53

Cu-mediated formation of nonracemic cis- or trans- 2-substituted cyclopropylboronates.

Scheme 54

Cu-catalyzed synthesis of γ,γ-gem-difluoroallylboronates.

Scheme 55

Cu-catalyzed hydrofunctionalization of internal alkenes and vinylarenes.

Scheme 56

Cu-catalyzed Markovnikov and anti-Markovnikov borylation of alkenes.

Scheme 57

Cu-catalyzed borylation/ortho-cyanation/Cope rearrangement.

Scheme 58

Borylfluoromethylation of alkenes.

Scheme 59

Cu-catalyzed synthesis of tertiary nonracemic alcohols.

Scheme 60

Synthesis of densely functionalized and synthetically versatile 1,2- or 4,3-borocyanated 1,3-butadienes.

Scheme 61

Cu-catalyzed trifunctionalization of allenes.

Scheme 62

Cu-catalyzed selective arylborylation of arenes.

Scheme 63

Asymmetric borylative coupling between styrenes and imines.

Scheme 64

Regio-divergent aminoboration of unactivated terminal alkenes.

Scheme 65

Cu-catalyzed 1,4-borylation of α,β-unsaturated ketones.

Scheme 66

Cu-catalyzed protodeboronation of α,β-unsaturated ketones.

Scheme 67

Cu-catalyzed β-borylation of α,β-unsaturated imines.

Scheme 68

Cu-catalyzed synthesis of β-trifluoroborato carbonyl compounds.

Scheme 69

Asymmetric 1,4-borylation of α,β-unsaturated carbonyl compounds.

Scheme 70

Cu-catalyzed ACB and ACA reactions of α,β-unsaturated 2-acyl-N-methylimidazoles.

Scheme 71

Cu-catalyzed diborylation of aldehydes.

Scheme 72

Umpolung pathway for chiral, nonracemic tertiary alcohol synthesis (top) and proposed mechanism for product formation of 456 and 457 (bottom).

Scheme 73

Cu-catalyzed synthesis of α-hydroxyboronates.

Scheme 74

Cu-catalyzed borylation of ketones.

Scheme 75

Cu-catalyzed borylation of unactivated alkyl halides.

Scheme 76

Cu-catalyzed borylation of allylic difluorides.

Scheme 77

Cu-catalyzed borylation of cyclic and acyclic alkyl halides.

Scheme 78

Cu-catalyzed borylation of unactivated alkyl chlorides and bromides.

Scheme 79

Cu-catalyzed decarboxylative borylation of carboxylic acids.

Scheme 80

Cu-catalyzed borylation of benzylic, allylic, and propargylic alcohols.