Synergistic Strategies in Aminocatalysis

Abstract

Synergistic catalysis offers the unique possibility of simultaneous activation of both the nucleophile and the electrophile in a reaction. A requirement for this strategy is the stability of the active species towards the reaction conditions and the two concerted catalytic cycles. Since the beginning of the century, aminocatalysis has been established as a platform for the stereoselective activation of carbonyl compounds through HOMO-raising or LUMO-lowering. The burgeoning era of aminocatalysis has been driven by a deep understanding of these activation and stereoinduction modes, thanks to the introduction of versatile and privileged chiral amines. The aim of this review is to cover recent developments in synergistic strategies involving aminocatalysis in combination with organo-, metal-, photo-, and electro-catalysis, focusing on the evolution of privileged aminocatalysts architectures.

Keywords: aminocatalysis; asymmetric catalysis; electrocatalysis; organocatalysis; photoredox catalysis; synergistic catalysis.

Figure 1

Principal activation modes and privileged catalysts in aminocatalysis.

Figure 2

Comparison between the monocatalytic approach (LUMO‐lowering), synergistic catalysis, and differentiating catalysis.

Scheme 1

α‐Alkylation of aldehydes by synergistic amino/Brønsted acid catalysis.

Scheme 2

γ‐Alkylation of α‐branched enals by synergistic amino/Brønsted acid catalysis.

Scheme 3

a) Synegistic enamine‐/Brønsted acid‐catalyzed α‐addition of 4‐vinyl pyridines to aldehydes. b) Formal [4+2] cycloaddition of dienals to 4‐vinyl quinolines.

Scheme 4

Trienanmine‐catalyzed [4+2] cycloaddition of dienals on ortho‐formyl cinnamates.

Scheme 5

Allylation of α‐branched aldehydes through synergistic enamine/Lewis acid catalysis.

Scheme 6

Asymmetric disulfuration of α‐branched keto‐esters through synergistic enamine/FLP catalysis.

Scheme 7

a) [4+2] cycloaddition of vinylogous malononitriles to enals by iminium ion/Brønsted base catalysis; b) [4+2] cycloaddition of vinylogous 2‐methylindolyl methyl‐enemalononitriles to enals.

Scheme 8

Synergistic iminium ion/Brønsted base catalysis assisted by counter‐anion binding.

Scheme 9

Differentiating catalysis in [4+2] cycloaddition.

Scheme 10

Synergistic chiral amine/ketone catalysis for the α‐oxygenation of encumbered carbonyl compounds.

Scheme 11

Synergistic enamine/Pd⁰ α‐alkylation of aldehydes.

Scheme 12

General mechanism for amino‐metal synergistic catalysis.

Scheme 13

Synthesis of allyl‐ammonium salts.

Scheme 14

Enantioselective synthesis of α‐disubstituted chiral vinyl aldehydes.

Scheme 15

Enantioselective functionalization of linear aldehydes with an enolizable proton.

Scheme 16

α‐Alkylation of aldehydes with simple alkynes.

Scheme 17

Primary amine/Rh synergistic asymmetric catalysis for the allylation of α‐branched ketones.

Scheme 18

Synergistic strategies for the α‐allylation of encumbered carbonyl compounds.

Scheme 19

Stereoselective synthesis of β‐keto esters.

Scheme 20

Enantioselective synthesis of α‐branched ketone derivatives through directing group assistance.

Scheme 21

Asymmetric addition of monoepoxides and allyl epoxides to 1,3 carbonyl derivatives.

Scheme 22

Enatio‐ and diasterodivergent hydroalkylation for the synthesis of enantiopure vinyl aldehydes.

Scheme 23

Enantioselective α‐allylation of aldehydes by asymmetric counter‐anion directed catalysis.

Scheme 24

Enantioselective α‐allylation of aldehydes with allylic alcohols with chiral diamines.

Scheme 25

Asymmetric cyclopropanation of bonzoxazoles.

Scheme 26

Asymmetric synthesis of cyclopenta[b]indole derivatives through [3+2] transformation.

Scheme 27

Cooperative procedure for the enantioselective synthesis of spiro derivatives.

Scheme 28

Synergistic enamine/photoredox catalysis for α‐functionalization of carbonyl compounds.

Scheme 29

a) General catalytic cycle for the synergistic amino/photoredox α‐alkylation of aldehydes with transition metal complexes as photocatalyst. b) Proposed radical chain mechanism.

Scheme 30

α‐Alkylation of aldehydes driven by EDA complexes.

Scheme 31

α‐Alkylation of aldehydes with simple olefins.

Scheme 32

α‐Alkylation of aldehydes with styrene‐driven enamine/photoredox/HAT synergistic catalysis.

Scheme 33

α‐Alkylation of aldehydes with bromomalonate driven by synergistic ground‐/photoexcited‐state enamine catalysis.

Scheme 34

β‐Arylation of saturated carbonyl compounds through enamine/Ir^III synergistic catalysis.

Scheme 35

Mechanistic insight into the synergistic enamine/photoredox/biocatalysis of the DKR of β‐substituted cyclic ketones.

Scheme 36

Deracemization of α‐branced aldehydes by synergistic use of aminocatalysis and light.

Scheme 37

a) Synergistic enamine‐/photocalytic‐mediated α‐alkylation of aldehydes with different chlorides; b) Formation of a relatively weak C−S bond and consequently the electrophilic radical B.

Figure 3

a) Challenges in radical addition to iminium ion intermediates. b) Aminocatalyzed reduction through intramolecular SET of the α‐iminyl radical cation followed by the formation of the photoactive catalyst D.

Scheme 38

Amino‐photoredox synergistic methodology for the stereoselective formation of β,β‐disubstituted cycloketones with benzodioxole or anilines.

Scheme 39

Functionalization of ketones with various silylated radical precursors through intramolecular EDA complex formation.

Scheme 40

Melchiorre et al.′s investigation of the photoredox behavior of the iminium ion.

Scheme 41

Mechanistic insight into the β‐functionalization of aldehydes through synergistic ground‐state/photoexcited‐state iminium ion catalysis.

Scheme 42

Enantioselective β‐benzylation of enals with toluene derivatives.

Scheme 43

β‐Alkylation of aliphatic and aromatic α,β‐unsaturated aldehydes through synergistic iminium ion/photoredox catalysis.

Scheme 44

Electrooxidation of enamines in methanol.

Scheme 45

α‐Functionalization of different enamines with dicarbonyl compounds.

Scheme 46

α‐Oxyamination of aldehydes through enamine/electro synergistic catalysis.

Scheme 47

Stereoselective α‐arylation/hemiacetalization of aldehydes through enamine/electro synergistic catalysis.

Scheme 48

Enantioselective enamine‐/electrochemically driven coupling of aldehydes with xantene.

Scheme 49

Asymmetric α‐alkylation of ketones by synergistic combination of amino‐ and electro‐catalysis C−H functionalization of ketones.

Scheme 50

Synthesis of quaternary indolin‐3‐ones.

Scheme 51

Electrochemical 3‐functionalization of indoles.

Scheme 52

α‐Arylation of α‐branched ketones by means of synergistic use of aminocatalysis and electrochemistry.