Base Cooperative Catalysis Research Articles

Pd-H/Lewis base cooperative catalysis confers asymmetric allylic alkylation of esters atom-economy and stereodivergence

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Achiral Cp*Rh(III)/Chiral Lewis Base Cooperative Catalysis for Enantioselective Cyclization via C-H Activation.

An enantioselective [4+3] cyclization via C(sp2)-H activation with a cooperative catalytic system consisting of a Cp*Rh(III) complex and a chiral Lewis base is described. An α,β-unsaturated acyl ammonium intermediate is generated from a chiral isochalcogenurea catalyst and an acyl fluoride reacts with a metallacycle generated from the Cp*Rh catalyst and a benzylamine derivative. This cooperative catalytic system gives a variety of benzolactams in good yields with excellent enantioselectivities (up to 99:1 er). The results demonstrated that chiral Lewis base catalysis is a powerful tool for controlling the enantioselectivity of transition metal-catalyzed C-H functionalizations.

Direct Asymmetric α‐Selective Mannich Reaction of β,γ‐Unsaturated Ketones with Cyclic α‐Imino Ester: Divergent Synthesis of Cyclocanaline and Tetrahydro Pyridazinone Derivatives

The first regio-, diastereo-, and enantioselective direct Mannich reaction of β,γ,-unsaturated ketones with benzoxazinone cyclic imines was enabled by Lewis acid/Brønsted base cooperative catalysis. The dinuclear zinc complex catalyzed the reaction of a broad range of β,γ-unsaturated ketones to proceed at the α-site exclusively, leading to corresponding adducts with two consecutive tertiary carbon stereocenters in diastereomeric ratios of up to >20:1 and enantioselectivities generally in the 90-99 % ee range. These products were used as general intermediates in the synthesis of multisubstituted cyclocanalines, tetrahydro pyridazinones, and 4H-furo[2,3-b][1,4]benzoxazine derivatives.

Copper/Lewis base cooperatively catalyzed asymmetric allylic alkylation of Morita-Baylis-Hillman carbonates with azomethine ylides.

In this paper, an asymmetric allylic alkylation of easily available azomethine ylides with Morita-Baylis-Hillman (MBH) carbonates through a copper (i)/Lewis base cooperative catalysis strategy has been realized. The co-catalyzed asymmetric allylic alkylation provided the corresponding amino acid derivatives in up to 90% yields with up to 99% ee as well as good to excellent regioselectivity.

Direct enolization chemistry of 7-azaindoline amides: A case study of bis(tetrahydrophosphole)-type ligands

7-Azaindoline amides are particularly useful in direct enolization chemistry due to their facilitated enolization in soft Lewis acid/Brønsted base cooperative catalysis. The Cu(I) complex of (R,R)-Ph-BPE, a bis(tetrahydrophosphole)-type chiral bisphosphine ligand, exhibits consistently high catalytic performance and stereoselectivity irrespective of the nature of the α-substituent of the amides. Unexpectedly, however, alkyl-substituted bis(tetrahydrophosphole)-type ligands have substantially inferior catalytic performance. Evaluation of the optimized structures of Cu(I)/amide and Cu(I)/enolate complexes provided clues to dissecting the diverted reaction outcomes.

Insights into chemoselective fluorination reaction of alkynals via N-heterocyclic carbene and Brønsted base cooperative catalysis

A systematically theoretical study has been carried out to understand the mechanism and chemoselectivity of N-heterocyclic carbene (NHC)-catalyzed fluorination reaction of alkynals using density functional theory calculations. The calculated results reveal that the reaction contains several steps, i.e., formation of the actual catalyst NHC, the nucleophilic attack of NHC on the carbonyl carbon atom of a formyl group, the formation of Breslow intermediate, the removal of methyl carbonate group to afford cumulative allenol intermediate, C–F bond formation coupled with generation of (SO2Ph)2N− anion, esterification accompanied with formation of (SO2Ph)2NH, and dissociation of NHC from product. For the formation of Breslow intermediate via the [1,2]-proton transfer process, apart from the direct proton transfer mechanism, the H2O- and EtOH-mediated proton transfer mechanisms were also investigated, and the free energy barriers for the crucial proton transfer steps can be significantly lowered by explicit inclusion of the protic media EtOH. Furthermore, multiple analyses have also been performed to explore the roles of catalysts and origin of chemoselectivity. Noteworthily, the in situ formed Bronsted base (BB) (SO2Ph)2N− anion was found to play an indispensable role in the esterification process, indicating that the reaction undergoes NHC-BB cooperatively catalytic mechanism, which is remarkably different from the direct esterification pathway proposed in the experimental references. This theoretical work provides a case on the exploration of the dual catalysis in NHC chemistry, which is valuable for rational design on newly cooperative organocatalysis in future.

Direct Catalytic Asymmetric Aldol Reaction of α-Alkylamides.

A catalytic asymmetric aldol reaction directly employing amides as latent enolates has remained elusive because of the resistance of amides to enolization. A direct aldol reaction of α-alkylamides without any electron-withdrawing group harnessed by specific activation of 7-azaindoline amides under soft Lewis acid/Brønsted base cooperative catalysis is reported. Diastereo- and enantioselective coupling with ynals and aromatic aldehydes as well as divergent functional group interconversion of the amide provided expeditious access to a variety of aliphatic and aromatic chiral building blocks.

Managing the retro-pathway in direct catalytic asymmetric aldol reactions of thioamides.

Thioamides are the preferred pronucleophiles for direct catalytic asymmetric aldol reactions in the context of soft Lewis acid/hard Brønsted base cooperative catalysis. In-depth investigation of this proton-transfer catalysis, which is virtually in equilibrium, revealed that the prominence of the retro-aldol reaction depended on the substrate combination. The retro-aldol reaction is a serious issue in direct aldol reactions because the product distribution, including enantiomers and diastereomers, is governed by thermodynamic parameters, and the aldol products are obtained in much lower stereoselectivity compared with the kinetically controlled process. Herein we report the beneficial effect of an additive with a functional group architecture similar to that of the aldol adduct that suppresses the retro-aldol reaction by competitively binding to the catalyst. Strategic use of the additive led to high stereoselectivity, even when the combination of substrates was prone to the retro-aldol reaction.

Iterative direct aldol strategy for polypropionates: enantioselective total synthesis of (-)-membrenone A and B.

An iterative direct aldol reaction using a C3 propionate unit as an aldol donor offers expeditious access to polyketide assembly in a highly diastereo- and enantioselective manner. An all-syn polyketide array with four consecutive stereogenic centers was efficiently constructed by an aldol reaction of thiopropionamide via soft Lewis acid/hard Brønsted base cooperative catalysis. This iterative aldol strategy led to an enantioselective synthesis of (-)-membrenone A and B.

ChemInform Abstract: Changing the Reaction Pathway by NHC/Broensted Base Cooperative Catalysis: Highly Stereoselective Synthesis of Multifunctional Benzo[a]fluoren‐11‐ones from the Dimerization of 2‐(Aroylvinyl)arylaldehydes.

AbstractThe unprecedented title synthesis requires both the triazole catalyst and 4‐methoxyphenolate as a co‐catalyst and proceeds via a benzoin‐Michael‐Michael cascade reaction sequence.

ChemInform Abstract: Direct Catalytic Asymmetric Addition of Acetonitrile to N‐Thiophosphinoylimines.

AbstractSoft Lewis acid‐hard Broensted base cooperative catalysis to activate both acetonitrile (II) and phosphinoylimine (I) is found to be crucial to promote the elusive C—C bond‐forming reaction in an enantioselective fashion.

Changing the Reaction Pathway by NHC/Brønsted Base Cooperative Catalysis: Highly Stereoselective Synthesis of Multifunctional Benzo[a]fluoren-11-ones from the Dimerization of 2-(Aroylvinyl)arylaldehydes

The unprecedented NHC/Brønsted base-cocatalyzed dimerization reaction of 2-(aroylvinyl)arylaldehydes was reported. In the presence of a triazole carbene catalyst alone, no reaction of 2-(aroylvinyl)arylaldehydes was observed. However, the combination of triazole carbene and 4-methoxyphenolate efficiently catalyzed the dimerization of 2-(aroylvinyl)arylaldehydes to proceed through a benzoin-Michael-Michael reaction cascade, producing 6-aroyl-5-(aroylmethyl)-11a-hydroxybenzo[a]fluoren-11-ones as the sole diastereomers in good yields.

Direct catalytic asymmetric addition of acetonitrile to N-thiophosphinoylimines

Direct catalytic addition of acetonitrile pronucleophiles to thiophosphinoylimines is described. Soft Lewis acid-hard Brønsted base cooperative catalysis is crucial to promote this elusive carbon-carbon bond-forming reaction in an enantioselective fashion.

Direct Catalytic Asymmetric Addition of Allylic Cyanides to Aldehydes for Expeditious Access to Enantioenriched Unsaturated δ‐Valerolactones

A direct catalytic asymmetric γ-addition of allyl cyanide to aldehydes promoted by soft Lewis acid/hard Brønsted base cooperative catalysis is described. The resulting homoallylic alcohols bearing a Z-configured α,β-unsaturated nitrile allow rapid access to enantioenriched δ-valerolactones.

Direct Catalytic Asymmetric Conjugate Addition of Terminal Alkynes to α,β-Unsaturated Thioamides

Direct catalytic asymmetric conjugate addition of terminal alkynes to alpha,beta-unsaturated thioamides under proton transfer conditions is described. Soft Lewis acid/hard Brønsted base cooperative catalysis is crucial for simultaneous activation of terminal alkynes and thioamides, affording the beta-alkynylthioamides in a highly enantioselective manner. Control experiments suggested that the intermediate copper thioamide enolate can work as Brønsted base to drive the catalytic cycle via proton transfer. The divergent transformation of the thioamide functionality highlights the synthetic utility of the alkynylation products.