Asymmetric ion-pairing catalysis

Abstract

Charged intermediates and reagents are ubiquitous in organic transformations. The interaction of these ionic species with chiral neutral, anionic, or cationic small molecules has emerged as a powerful strategy for catalytic, enantioselective synthesis. This review describes developments in the burgeoning field of asymmetric ion-pairing catalysis with an emphasis on the insights that have been gleaned into the structural and mechanistic features that contribute to high asymmetric induction.

Figure 1

Types of asymmetric ion-pairing catalysis.

Figure 2

Types of ion pairs.

Figure 3

Comparative directionality of catalyst-substrate interactions of common asymmetric catalysis strategies (L_n* = chiral ligand; B*H = chiral Brønsted acid; X* = chiral counterion)

Figure 4

Structures of chiral ammonium phase-transfer catalysts.

Figure 5

(a) Tetrahedron stereoselectivity model for cinchona alkaloid-derived catalysts and the proposed enolate approach based on (b) the optimal geometry for attractive R₃N⁺–C–H•••X bonds in the [Me₃NH•CH₂COOMe] complex at the MP2/6-311++G** level of theory.

Figure 6

Proposed internal hydrogen-bonding via a water molecule for catalysts 1e–h and enantioselectivity in the benzylation of 4.

Figure 7

X-ray crystal structure of N-spiro binaphthyl catalyst (2)•PF₆⁻ (adapted from reference 28).

Figure 8

Optimized structure of a tartrate-derived diammonium catalyst (3)•enolate ion pair at the B3LYP/6-31G(d) level of theory.

Figure 9

Representative chiral phosphonium phase-transfer catalyst structures.

Figure 10

Cation binding by chiral polyether catalysts.

Figure 11

Types of ion-pairing interactions.

Figure 12

BINOL-derived phosphate anions 14.

Figure 13

Acidity of phosphoric acid versus N-triflylphosphoramide catalysts.^[–87]

Figure 14

Substrate recognition site created by the 3,3′-substituents (G) of chiral BINOL-derived anions (Y = O, S; X = O, NTf).

Figure 15

Modes of electrophile activation by dual hydrogen-bond donors.

Scheme 1

First reported enantioselective phase-transfer-catalyzed alkylation of indanone derivatives.

Scheme 2

(a) Enantioselective alkylation of glycine ester 4 catalyzed by various quaternary ammonium ions and (b) the interfacial mechanism for phase-transfer catalysis.

Scheme 3

Tetraaminophosphonium salt 8 as a supramolecular chiral organic base catalyst for conjugate additions to acylbenzotriazoles.

Scheme 4

Chiral crown ethers as phase-transfer cation-binding catalysts for enantioselective Michael addition reactions.

Scheme 5

Bis(hydroxy) polyether-catalyzed desilylative kinetic resolution of silyl-protected secondary alcohols.

Scheme 6

Proof-of-concept studies using chiral borate anions.

Scheme 7

Chiral borate anion-directed aziridinium opening reaction.

Scheme 8

Comparison of enantioselective transfer hydrogenations of enals via iminium catalysis by (a) chiral ammonium- or (b) chiral anion-based salts.

Scheme 9

(a) Scope and (b) mechanism for the epoxidation of enals catalyzed by chiral secondary ammonium•phosphate salts.

Scheme 10

(a) Enantioselective phosphoric acid-catalyzed N-acyliminium ion cyclization cascade and (b) the proposed mechanism.

Scheme 11

(Thio)phosphoric acid-catalyzed enantioselective N-alkylation of indoles with cyclic N-acyliminium ion intermediates.

Scheme 12

Phosphoric acid-catalyzed Pictet-Spengler reaction proceeding via (a) sulfenyliminium ions or (b) dialkyl iminium ions.

Scheme 13

Enantioselective phosphoric acid-catalyzed pinacol rearrangement.

Scheme 14

Cooperative dienamine and ion-pairing catalysis for the δ-alkylation of α–branched enals.

Scheme 15

Phosphoric acid-catalyzed enantioselective transacetalization reactions.

Scheme 16

a) Aldol-type reaction and (b) semipinacol rearrangement of oxocarbenium ions formed in situ by the protonation of vinyl ethers.

Scheme 17

(a) Desymmetrization of meso-aziridinium ions by chiral phosphate-directed PTC and (b) the proposed catalytic cycle for this application of chiral anion PTC compared to chiral cation PTC (X = halide, B = basic anion, A* = chiral anion, Q* = chiral cation, M = alkali metal).

Scheme 18

Enantioselective fluorocyclization of olefins and fluorination of enamides by chiral anion PTC.

Scheme 19

Chiral phosphate-directed desymmetrization of (a) meso-episulfonium and (b) meso-halonium ions.

Scheme 20

Chiral phosphate-directed Au(I)-catalyzed enantioselective hydrofunctionalization of allenes.

Scheme 21

N-triflylphosphoramide-catalyzed nucleophilic addition to (a) N-alkylindolium and (b) N-acyliminium ions.

Scheme 22

Organocatalytic enantioselective allylic alkylation reaction.

Scheme 23

N-triflyl thiophosphoramide-catalyzed enantioselective protonation of silyl enol ethers.

Scheme 24

(a) Enantioselective disulfonimide-catalyzed Mukaiyama aldol reaction and (b) the proposed in situ silylation of the catalyst.

Scheme 25

Enantioselective spiroacetalization catalyzed by an exceptionally bulky imidodiphosphoric acid.

Scheme 26

Acetalization by thiourea-assisted orthoester hydrolysis through anion-binding.

Scheme 27

(a) Thiourea-catalyzed tetrahydropyranylation of alcohols by anion-binding and (b) a comparison of transition structures for the uncatalyzed and thiourea-catalyzed addition of methanol to dihydropyran at the B3LYP/6-31G(d,p) level of theory (adapted from reference 105).

Scheme 28

(a) Thiourea-catalyzed enantioselective Strecker reaction, (b) potential activation mechanisms, and (c) correlation of selected, calculated transition structure hydrogen-bond lengths with enantioselectivity for the hydrocyanation of N-benzhydryl pivaldimine. for eight structurally distinct thiourea catalysts.

Scheme 29

Thiourea-catalyzed acylcyanation of imines.

Scheme 30

Thiourea-catalyzed (a) acyl-Pictet-Spengler and (b) acyl-Mannich reactions proceeding via N-acyliminium ions.

Scheme 31

Pictet-Spengler-type cyclization of hydroxylactams and the proposed anion-binding mechanism.

Scheme 32

Thiourea-catalyzed enantioselective Petasis-type reaction of quinolines proceeding via N-acylquinolinium ions.

Scheme 33

(a) Effect of thiourea catalyst aromatic group on the efficiency and enantioselectivity of the bicyclization of hydroxylactam 37 and (b) the proposed stabilizing cation–π interaction in the dominant transition state.

Scheme 34

Enantioselective thiourea-catalyzed addition of silyl ketene acetals to oxocarbenium ions.

Scheme 35

Enantioselective, catalytic S_N1-type alkylation of aldehydes with benzhydryl cations.

Scheme 36

Thiourea-catalyzed enantioselective protio-Pictet-Spengler reaction with rate-determining rearomatization.

Scheme 37

Enantioselective oxidopyrilium-based [5+2] cycloaddition via anion-binding/enamine co-catalysis.

Scheme 38

Acylative kinetic resolution of primary amines by an anion-binding approach to nucleophilic catalysis.

Scheme 39

Enantioselective acylation of silyl ketene acetals by an anion-binding approach to nucleophilic catalysis.

Scheme 40

Dual catalysis approach to the enantioselective Steglich rearrangement and addition of O-acylated azlactones to isoquinolines.

Scheme 41

Urea-catalyzed enantioselective iodolactonization.

Scheme 42

(a) Urea/strong Brønsted acid co-catalyzed enantioselective Povarov reaction (NBSA = o-nitrobenzenesulfonic acid), and energy and geometry-minimized structures of (b) the ground state catalyst-substrate interactions (Ar = 3,5-(CF₃)₂C₆H₃) and (c) the cycloaddition transition structure leading to the major enantiomer of product at the B3LYP/6-31G(d) level of theory.