N‐Heterocyclic Carbene‐Mediated Organocatalytic Transfer of Tin onto Aldehydes: New Access to α‐Silyloxyalkylstannanes and γ‐Silyloxyallylstannanes

A new, highly efficient and mild N‐heterocyclic carbene (NHC)‐mediated organocatalytic procedure for the transfer of tin from tributyl(trimethylsilyl)stannane (Bu₃SnSiMe₃) onto aldehydes for the preparation of α‐silyloxyalkylstannanes and γ‐silyloxyallylstannanes has been developed.     

N‐Heterocyclic Carbene‐Mediated Enantioselective Addition of Phenols to Unsymmetrical Alkylarylketenes

Chiral N‐heterocyclic carbenes (NHCs) mediate the enantioselective addition of 2‐phenylphenol to unsymmetrical alkylarylketenes, delivering α‐alkyl‐α‐arylacetic acid derivatives with good levels of enantiocontrol (up to 84% ee). Enantiodivergent stereochemical outcomes are observed using 2‐phenylphenol and benzhydrol in the NHC‐promoted esterification reaction using a triazolium precatalyst derived from pyroglutamic acid, consistent with distinct mechanistic pathways operating within these processes.     

N‐Heterocyclic Carbene‐Catalyzed Oxidative Amidation of Aldehydes with Amines

The N‐heterocyclic carbene (NHC)‐catalyzed oxidative amidation of aromatic aldehydes with amines in the presence of N‐bromosuccinimide (NBS) as an oxidant has been developed for the synthesis of amides. This amidation strategy is tolerant to both the electronic and the steric nature of the aryl aldehydes employed. The present methodology was extended to chiral amino acid derivatives to generate the corresponding amides in good yields and excellent ee values (>98%).

     

Enantioselective N‐Heterocyclic Carbene‐Catalyzed [3+3] Annulation of α,β‐Unsaturated Esters with Methyl Ketoimine

Herein, we disclose the N‐heterocyclic carbene (NHC)‐catalyzed [3+3] annulation of challenging esters with methyl ketoimines for the highly enantioselective synthesis of intriguing δ‐lactams featuring various substituent patterns. The annulation occurs under mild conditions and offers good tolerance, good yields and excellent enantioselectivities. The six‐membered heterocyclic products are valuable for the synthesis of bioactive molecules.

     

Enantioselective Synthesis of cis‐4‐Formyl‐β‐lactams via Chiral N‐Heterocyclic Carbene‐Catalyzed Kinetic Resolution

An efficient synthesis of optically pure cis‐4‐formyl‐β‐lactams (up to 99% ee) by a chiral NHC‐catalyzed ring expansion reaction has been realized, featuring the ready availability of both the substrate and the catalyst, and the mild reaction conditions. The current method is also suitable for the synthesis of enantioenriched 4‐formyl‐β‐lactams and succinimides containing quaternary carbon centers.     

N‐Heterocyclic Carbene‐Catalyzed Benzoin Strategy for Divergent Synthesis of Cyclitol Derivatives from Alditols

A divergent synthesis of cyclitol derivatives has been developed utilizing an N‐heterocyclic carbene‐catalyzed benzoin‐type cyclization of C₂‐symmetrical dialdoses. The resulting inososes are versatile intermediates, which are readily converted into not only inositols but also amino‐, deoxy‐, O‐methyl‐ and C‐methyl‐inositols.

     

Microwave‐Assisted Synthesis of N‐Heterocyclic Carbene‐ Palladium(II) Complexes

The microwave‐assisted synthesis of two different types of N‐heterocyclic carbene‐palladium(II) complexes, (NHC)Pd(acac)Cl (NHC=N‐heterocyclic carbene; acac=acetylacetonate) and (NHC)PdCl₂(3‐chloropyridine), has been carried out. A drastic reduction in reaction times (20 to 88 times faster, depending on the complex) was observed when compared to the previously described, conventionally‐heated synthesis of these complexes. The protocol also allowed for the synthesis of (IPr)Pd(acac)Cl [IPr=1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene] on a 5‐mmol scale in 30 min, with the reactants loaded in air.     

An Efficient and Recyclable Catalyst for N‐Alkylation of Amines and β‐Alkylation of Secondary Alcohols with Primary Alcohols: SBA‐15 Supported N‐Heterocyclic Carbene Iridium Complex

A mesoporous silica (SBA‐15)‐supported pyrimidine‐substituted N‐heterocyclic carbene iridium complex was prepared and used as a catalyst for both environmentally friendly N‐alkylation of amines and β‐alkylation of secondary alcohols with primary alcohols. The structure of the supported iridium catalyst was characterized by Fourier transform infrared (FT‐IR), ¹³C and ²⁹Si solid‐state nuclear magnetic resonance (NMR), small‐angle X‐ray scattering (SAXS), transmission electron microscopy (TEM), iridium K‐edge X‐ray absorption near‐edge structure (XANES) and extended X‐ray absorption fine structure (EXAFS) spectroscopic analyses which demonstrated that the coordination environment of the iridium centre and the 3‐dimensional‐hexagonal pore structure of SBA‐15 were retained after the immobilization. The catalyst was found to be highly efficient for both kinds of reaction on a wide range of substrates under mild conditions. Moreover, the supported iridium catalyst was obviously superior to the unsupported one in the N‐alkylation of aniline and β‐alkylation of 1‐phenylethanol with benzyl alcohol as substrate, which indicated that not only the iridium complex moiety but also the support material contributed to the catalytic activity of the supported iridium catalyst in these reactions. The supported iridium catalyst can be easily recycled by simple washing without chemical treatment, and exhibited excellent recycling performance without notable decrease in catalytic efficiency even after twelve test cycles for N‐alkylation of aniline with benzyl alcohol, nine cycles for N‐alkylation of different amines with different alcohols, and eight cycles for β‐alkylation of 1‐phenylethanol with benzyl alcohol, respectively.     

N‐Heterocyclic Carbene‐Catalyzed Enantioselective Annulation of Bromoenal and 1,3‐Dicarbonyl Compounds

Highly enantioselective [3+3] annulation reactions of bromoenals and 1,3‐dicarbonyl compounds are reported. In addition, both enantiomers of the resultant dihydropyranone could be easily obtained by choosing N‐heterocyclic carbenes (NHCs) with the same stereocenter but different substituents under the optimized reaction conditions.     

Enantioselective N‐Heterocyclic Carbene‐Catalyzed Annulations of 2‐Bromoenals with 1,3‐Dicarbonyl Compounds and Enamines via Chiral α,β‐Unsaturated Acylazoliums

The N‐heterocyclic carbene (NHC)‐catalyzed generation of chiral α,β‐unsaturated acylazoliums from 2‐bromoenals followed by their interception with 1,3‐dicarbonyl compounds or enamines, the formal [3+3] annulation reaction, is reported. The reaction results in the enantioselective synthesis of synthetically and medicinally important dihydropyranones and dihydropyridinones, and tolerates a wide range of functional groups. It is noteworthy that the reaction takes place under mild reaction conditions utilizing relatively low catalyst loadings. In addition, based on DFT calculations, a mechanistic scenario involving the attack of the nucleophile from below the plane of the α,β‐unsaturated acylazoliums, and the mode of enantioinduction is presented.     

Enantioselective Synthesis of Dihydrocoumarins via N‐Heterocyclic Carbene‐Catalyzed Cycloaddition of Ketenes and o‐Quinone Methides

Chiral N‐heterocyclic carbenes were found to be efficient catalysts for the formal [4+2] cycloaddition reaction of alky(aryl)ketenes and o‐quinone methides to give the corresponding 3,3,4‐trisubstituted 3,4‐dihydrocoumarins in good yields with good diastereoselectivities and excellent enantioselectivities.     

Cyclometalated N‐Heterocyclic Carbene‐Platinum Catalysts for the Enantioselective Cycloisomerization of Nitrogen‐Tethered 1,6‐Enynes

Platinum(II) complexes which combine six‐membered N‐heterocyclic carbene‐containing metallacyclic units and monodentate chiral phosphines have been prepared. The key step of their synthesis is the intramolecular oxidative addition of N‐2‐iodobenzylimidazolylidene‐platinum(0)‐diene complexes in the presence of the chiral phosphorus ligands. The platinum(II) metallacycles have been used as well‐defined pre‐catalysts for the enantioselective cycloisomerization of nitrogen‐tethered 1,6‐enynes into 3‐azabicyclo[4.1.0]hept‐4‐enes. High enantiomeric excesses have been obtained with either Monophos or phenyl‐Binepine based catalysts (ees=82–96%), although phenyl‐Binepine outperforms Monophos in these reactions. The absolute configuration of the final 3‐azabicyclo[4.1.0.]heptenes has been established by X‐ray diffraction studies. The method has been extended then to the cycloisomerization of dienynes with enantiotopic vinyl groups. An (S)‐phenyl‐Binepine‐platinum(II) complex allows total diastereoselectivity and high enantioselectivity levels to be attained in these reactions (ees up to 95%) which represent the first enantioselective desymetrizations achieved via enyne cycloisomerizations.     

Electrogenerated N‐Heterocyclic Carbene in Ionic Liquid: An Insight into the Mechanism of the Oxidative Esterification of Aromatic Aldehydes

An N‐heterocyclic carbene (NHC), generated by cathodic reduction of BMIm BF₄, mediates the oxidative esterification of aromatic aldehydes with organic bromides in the corresponding ionic liquid as solvent. The product recovery by simple extractive work‐up with diethyl ether allowed the ionic liquid to be recycled up to 9 times for subsequent electrolyses, with no significant loss in the product yield. The isolation of an intermediate, whose structure was confirmed by synthesis and transformation into the ester, provided the key for a mechanistic insight into the reaction.

     

Direct and Transfer Hydrogenation of Ketones and Imines with a Ruthenium N‐Heterocyclic Carbene Complex

The dihydride ruthenium N‐heterocyclic carbene complex Ru(IMes)(PPh₃)₂CO(H)₂ ( 1 ) (IMes=1,3‐dimesityl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene) is an efficient catalyst for both direct hydrogenation and transfer hydrogenation of ketones and imines, in the absence of base.     

N‐Heterocyclic Carbene‐Catalyzed Umpolung Formal [3+3] Cycloaddition of Enals with Isatogens: Access to Fused Indolin‐3‐ones with a Tetrasubstituted Carbon Stereocenter

A novel synthetic method to access fused indolin‐3‐ones with a tetrasubstituted carbon stereocenter has been developed via NHC‐catalyzed umpolung formal [3+3] cycloaddtion of enals with isatogens. This methodology could be also applied for the quick construction of the 6‐5‐5 tricyclic pyrrolo[1,2‐a]indole skeleton which is frequently found as a core structure of many indole alkaloids.

     

General Cycloaddition Between a Trimethylsilyl‐Capped Alkyne and an Azide Catalyzed by an N‐Heterocyclic Carbene‐Copper Complex and Pyridine‐Biscarboxamide

With an externally provided catalytic amide facilitator and an N‐heterocyclic carbene‐copper (NHC‐Cu) complex, the cycloaddition of an azide and a trimethylsilyl (TMS)‐capped alkyne can proceed smoothly. This protocol can be applied to a variety of TMS‐capped substrates, with electron‐rich alkynes generally giving higher yields and nitroaromatic alkynes giving lower yields. For special applications of this protocol, a substrate containing both a terminal alkyne and a TMS‐capped alkyne can sequentially react with different azides without isolation of intermediates; and a macrocyclic product can also be formed efficiently without the complication of polymer formation.

     

Beyond the Limits: Palladium‐N‐Heterocyclic Carbene‐Based Catalytic System Enables Highly Efficient [4+2] Benzannulation Reactions

A highly efficient catalytic system for the palladium‐catalyzed [4+2] benzannulation reaction of enynes and enynophiles has been developed. The use of an N‐heterocyclic carbene‐based palladium precursor allowed us to achieve turnover numbers up to 1800. The new catalytic system has enabled an expansion of the scope of the [4+2] homo‐benzannulation reaction.     

Synthesis of Valuable Chiral Intermediates by Isolated Ketoreductases: Application in the Synthesis of α‐Alkyl‐β‐hydroxy Ketones and 1,3‐Diols

Regio‐ and stereoselective reductions of α‐substituted 1,3‐diketones to the corresponding β‐keto alcohols or 1,3‐diols by using commercially available ketoreductases (KREDs) are described. A number of α‐monoalkyl‐ or dialkyl‐substituted symmetrical as well as non‐symmetrical diketones were reduced in high optical purities and chemical yields, in one or two enzymatic reduction steps. In most cases, two or even three out of the four possible diastereomers of α‐alkyl‐β‐keto alcohols were synthesized by using different enzymes, and in two examples both ketones were reduced to the 1,3‐diol. By replacing the α‐alkyl substituent with the OAc group, 1‐keto‐2,3‐diols, as well as 1,2,3‐triols were synthesized in high optical purities. These enzymatic reactions provide a simple, highly stereoselective and quantitative method for the synthesis of different diastereomers of valuable chiral synthons from non‐chiral, easily accessible 1,3‐diketones.