Chiral phosphines in nucleophilic organocatalysis

Abstract

This review discusses the tertiary phosphines possessing various chiral skeletons that have been used in asymmetric nucleophilic organocatalytic reactions, including annulations of allenes, alkynes, and Morita-Baylis-Hillman (MBH) acetates, carbonates, and ketenes with activated alkenes and imines, allylic substitutions of MBH acetates and carbonates, Michael additions, γ-umpolung additions, and acylations of alcohols.

Keywords: asymmetric catalysis; chiral phosphine; nucleophilic; organocatalysis; organophosphorus; synthesis.

Figure 1

Cyclic chiral phosphines based on bridged-ring skeletons.

Figure 2

Cyclic chiral phosphines based on binaphthyl skeletons.

Figure 3

Cyclic chiral phosphines based on ferrocene skeletons.

Figure 4

Cyclic chiral phosphines based on spirocyclic skeletons.

Figure 5

Cyclic chiral phosphines based on phospholane ring skeletons.

Figure 6

Acyclic chiral phosphines.

Figure 7

Multifunctional chiral phosphines based on binaphthyl skeletons.

Figure 8

Multifunctional chiral phosphines based on amino acid skeletons.

Scheme 1

Asymmetric [3 + 2] annulations of allenoates with electron-deficient olefins, catalyzed by the chiral bicyclic phosphine A2.

Scheme 2

Asymmetric [3 + 2] annulations of allenoate and enones, catalyzed by the chiral binaphthyl-based phosphepine B1.

Scheme 3

Asymmetric [3 + 2] annulations of N-substituted olefins and allenoates, catalyzed by the chiral binaphthyl-based phosphepine B4.

Scheme 4

Asymmetric [3 + 2] annulations of 2-aryl-1,1-dicyanoethylenes with ethyl allenoate, catalyzed by the chiral binaphthyl-based phosphepine B2.

Scheme 5

Asymmetric [3 + 2] annulations of 3-alkylideneindolin-2-ones with ethyl allenoate, catalyzed by the chiral binaphthyl-based phosphepine B2.

Scheme 6

Asymmetric [3 + 2] annulations of 2,6-diarylidenecyclohexanones with allenoates, catalyzed by the chiral binaphthyl-based phosphepine B2.

Scheme 7

Asymmetric [3 + 2] annulations of allenoate with alkylidene azlactones, catalyzed by the chiral binaphthyl-based phosphepine B2, and subsequent alcoholysis in methanol.

Scheme 8

Asymmetric [3 + 2] annulations of C₆₀ with allenoates, catalyzed by the chiral phosphine B6.

Scheme 9

Asymmetric [3 + 2] annulations of α,β-unsaturated esters and ketones with an allenoate, catalyzed by the ferrocene-modified phosphine C1.

Scheme 10

Asymmetric [3 + 2] annulations of exocyclic enones with allenoates, catalyzed by the ferrocene-modified phosphine C1.

Scheme 11

Asymmetric [3 + 2] annulations of enones with an allenylphosphonate, catalyzed by the ferrocene-modified phosphine C1.

Scheme 12

Asymmetric [3 + 2] annulations of 3-alkylidene-oxindoles with ethyl allenoate, catalyzed by the ferrocene-modified phosphine C1.

Scheme 13

Asymmetric [3 + 2] annulations of dibenzylideneacetones with ethyl allenoate, catalyzed by the ferrocene-modified phosphine C1.

Scheme 14

Asymmetric [3 + 2] annulations of trisubstituted alkenes with ethyl allenoate, catalyzed by the ferrocene-modified phosphine C1.

Scheme 15

Asymmetric [3 + 2] annulations of 2,6-diarylidenecyclohexanones with allenoates, catalyzed by the ferrocene-modified phosphine C1.

Scheme 16

Asymmetric [3 + 2] annulations of α,β-unsaturated ketones with ethyl allenoates, catalyzed by the ferrocene-modified phosphine C1.

Scheme 17

Asymmetric [3 + 2] annulations of α,β-unsaturated esters with allenoates, catalyzed by the ferrocene-modified phosphine C1.

Scheme 18

Asymmetric [3 + 2] annulations of alkylidene azlactones with allenoates, catalyzed by the chiral spiro phosphine D1.

Scheme 19

Asymmetric [3 + 2] annulations of α-trimethylsilyl allenones and electron-deficient olefins, catalyzed by the chiral phosphine E7.

Scheme 20

Asymmetric [3 + 2] annulations of α,β-unsaturated ketones with an allenone, catalyzed by the chiral phosphepine F1.

Scheme 21

Asymmetric [3 + 2] annulations of cyclic enones with allenoates, catalyzed by the chiral α-amino acid-based phosphine H1, and the proposed transition state.

Scheme 22

Asymmetric [3 + 2] annulations of arylidenemalononitriles and analogues with an allenoate, catalyzed by the chiral phosphine H5.

Scheme 23

Asymmetric [3 + 2] annulations of α,β-unsaturated esters with an allenoate, catalyzed by the chiral phosphine H10, and possible transition states.

Scheme 24

Asymmetric [3 + 2] annulations of 3,5-dimethyl-1H-pyrazole-derived acrylamides with an allenoate, catalyzed by the chiral phosphine H10.

Scheme 25

Asymmetric [3 + 2] annulations of maleimides with allenoates, catalyzed by the chiral phosphine H10.

Scheme 26

Asymmetric [3 + 2] annulations of α-substituted acrylates with allenoate, catalyzed by the chiral phosphine G6.

Scheme 27

Asymmetric [3 + 2] annulation of an N-tosylimine with an allenoate, catalyzed by the chiral phosphine F3.

Scheme 28

Asymmetric [3 + 2] annulations of N-tosylimines with an allenoate, catalyzed by the chiral phosphine F4.

Scheme 29

Asymmetric [3 + 2] annulations of N-tosylimines with an allenoate, catalyzed by the chiral phosphine B2.

Scheme 30

Asymmetric [3 + 2] annulations of N-diphenylphosphinoyl aromatic imines with butynoates, catalyzed by the chiral phosphine B2.

Scheme 31

Asymmetric [3 + 2] annulations of N-tosylimines with allenylphosphonates, catalyzed by the chiral phosphine B2.

Scheme 32

Asymmetric [3 + 2] annulation of an N-tosylimine with an allenoate, catalyzed by the chiral phosphine A3, and its application in the total synthesis of (+)-ibophyllidine.

Scheme 33

Asymmetric [3 + 2] annulations of N-diphenylphosphinoyl aromatic imines with allenoates (top), catalyzed by the chiral phosphine H3, and a possible transition state (bottom).

Scheme 34

Asymmetric [3 + 2] annulation of N-diphenylphosphinoylimines with allenoates, catalyzed by the chiral phosphine H12, and its application in the formal synthesis of (+)-trachelanthamidine.

Scheme 35

Asymmetric [3 + 2] annulation of an azomethine imine with an allenoate, catalyzed by the chiral phosphine D4.

Scheme 36

Asymmetric [3 + 2] annulations between α,β-unsaturated esters/ketones and 3-butynoates, catalyzed by the chiral phosphine F2.

Scheme 37

Asymmetric intramolecular [3 + 2] annulations of electron-deficient alkenes and MBH carbonates, catalyzed by the chiral phosphine D3.

Scheme 38

Asymmetric [3 + 2] annulations of methyleneindolinone and methylenebenzofuranone derivatives with MHB carbonates, catalyzed by the chiral phosphines (+)-E1 and (–)-E1, and possible transition states.

Scheme 39

Asymmetric [3 + 2] annulations of activated isatin-based alkenes with MBH carbonates, catalyzed by the chiral phosphine H2.

Scheme 40

Asymmetric [3 + 2] annulations of maleimides with MBH carbonates, catalyzed by the chiral phosphine H11.

Scheme 41

A series of [3 + 2] annulations of various activated alkenes with MBH carbonates, catalyzed by the chiral phosphine H4.

Scheme 42

Asymmetric [3 + 2] annulations of an alkyne with isatins, catalyzed by the chiral phosphine F1.

Scheme 43

Asymmetric [4 + 2] annulations catalyzed by the chiral phosphine B1.

Scheme 44

Asymmetric [4 + 2] annulations catalyzed by the chiral phosphine H5.

Scheme 45

Asymmetric [4 + 2] annulations catalyzed by the chiral phosphines H13 and H12.

Scheme 46

Asymmetric [4 + 2] annulations catalyzed by the chiral phosphine H6.

Scheme 47

Kerrigan’s [2 + 2] annulations of ketenes with imines, catalyzed by the chiral phosphine B7.

Scheme 48

Asymmetric [4 + 1] annulations, catalyzed by the chiral phosphine G6.

Scheme 49

Asymmetric homodimerization of ketenes, catalyzed by the chiral phosphine F5 and F6.

Scheme 50

Aza-MBH/Michael reactions, catalyzed by the chiral phosphine G1.

Scheme 51

Tandem RC/Michael additions, catalyzed by the chiral phosphine H14.

Scheme 52

Intramolecular tandem RC/Michael addition, catalyzed by the chiral phosphine H15.

Scheme 53

Double-Michael addition, catalyzed by the chiral aminophosphine G9.

Scheme 54

Tandem Michael addition/Wittig olefinations, mediated by the chiral phosphine BIPHEP.

Scheme 55

Asymmetric Michael additions, catalyzed by the chiral phosphines H7, H8, and H9.

Scheme 56

Asymmetric γ-umpolung additions, catalyzed by the chiral phosphine A1.

Scheme 57

Asymmetric γ-umpolung additions, catalyzed by the chiral phosphines E2 and E3.

Scheme 58

Intramolecular γ-additions of hydroxy-2-alkynoates, catalyzed by the chiral phosphine D2.

Scheme 59

Intra-/intermolecular γ-additions, catalyzed by the chiral phosphine D2.

Scheme 60

Intermolecular γ-additions, catalyzed by the chiral phosphines B5 and B3.

Scheme 61

Intermolecular γ-additions, catalyzed by the chiral phosphines E6 and B4.

Scheme 62

Asymmetric allylic substitution of MBH acetates, catalyzed by the chiral phosphine G2.

Scheme 63

Allylic substitutions between MBH acetates or carbonates and an array of nucleophiles, catalyzed by chiral binaphthyl-derived multifunctional phosphines.

Scheme 64

Asymmetric acylation of diols, catalyzed by the chiral phosphines E4 and E5.

Scheme 65

Kinetic resolution of secondary alcohols, catalyzed by the chiral phosphine E8 and E9.