Practical N-alkylation via homogeneous iridium-catalyzed direct reductive amination

Direct reductive amination(DRA)is one of the most efficient methods for amine synthesis.Herein we report a practical homogeneous DRA procedure utilizing iridium catalysis.Applying simple,readily available and inexpensive PPh_(3)and alike ligands along with iridium at a low loading,aldehydes and ketones reductively coupled with primary and secondary amines to efficiently form structurally and functionally diverse amine products,including a set of drugs and compounds from late-stage manipulation.The reaction conditions were exceptionally mild and additive-free,in which oxygen,moisture,polar protic groups and multiple other functional groups were tolerated.For targeted products,this methodology is especially versatile for offering multiple possible synthetic options.The 10 gram-scale synthesis further demonstrated the potential and promise of this procedure in practical amine synthesis.DFT studies reveal an“outer-sphere”H-addition pathway,in whichπ-πinteractions and H-bonding play important roles.

Partially biobased polymers:The synthesis of polysilylethers via dehydrocoupling catalyzed by an anionic iridium complex

Partially biobased polysilylethers(PSEs)are synthesized via dehydrocoupling polymerization catalyzed by an anionic iridium complex.Different types(AB type or AA and BB type)of monomers are suitable.Levulinic acid(LA)and succinic acid(SA)have been ranked within the top 10 chemicals derived from biomass.BB type monomers(diols)derived from LA and SA have been applied to the synthesis of PSEs.The polymerization reactions employ an air-stable anionic iridium complex bearing a functional bipyridonate ligand as catalyst.Moderate to high yields of polymers with number-average molecular weights(Mn)up to 4.38×104 were obtained.A possible catalytic cycle via an Ir-H species is presented.Based on the results of kinetic experiments,apparent activation energy of polymerization in the tempe rature range of 0-10℃is about 38.6 kJ/mol.The PSEs synthesized from AA and BB type monomers possess good thermal stability(T5=418℃to 437℃)and low glass-transition temperature(Tg=49.6℃).

Enantioselective synthesis of 10-allylanthrones via iridium-catalyzed allylic substitution reaction

A highly enantioselective allylic substitution reaction of anthrones with aromatic or aliphatic allyl carbonates was realized by using iridium catalyst prepared from [Ir（COD）CI]2 and BHPphos. Substituted 10-allylanthrones were obtained in excellent yields and with excellent enantioselectivity and regioselectivity （up to 98% yield, 99700 ee） under mild conditions.

Rapid Access to Polysubstituted Tetrahydrocarbazol-4-ones via Sequential Selective C—H Functionalization from N-Nitrosoanilines

Comprehensive Summary Herein,we have developed a strategy of Rh(III)-catalyzed C—H activation of N-nitrosoanilines and iodonium ylides to construct novel tetralydrocarbzol-4-one scaffolds,which provided valuable templates for sequential C—H functionalization such as alkylation,alkenylation,amidation and(hetero)arylation at C^(5)-position of tetralydrocarbzol-4-one with different coupling partners.Gram-scale synthesis and further transformations of tetralydrocarbzol-4-one derivatives to Ondansetron and its analogues demonstrated the utility of this protocol,which enabled the concise and diverse construction of biologically active molecules.

N-Acetylenethio phthalimides: Sequential linkage for compositional click reaction

Click chemistry has become a useful tool for diverse molecular linkage and modification, and the development of new click strategy that enable reversibility and multifunctionality is of high demand for the multifunction and drug release. Herein, compositionally clicking combined regioselective iridium-catalyzed azide-alkynthio cycloaddition(Ir-AAC) and disulfuration has been developed for the sequential linkage from N-acetylenethio phthalimides, naturally occurring thiols and readily available azides. This method has been successfully applied to the construction of drug hybrids, peptide modification and glycosylation. Furthermore, by the design of diacetylenethio phthalimide as a platform molecule, trifunctional conjugants were sequentially linked through independent Ir-AAC, disulfuration and Cu-AAC reaction for hydrophobic tagging ternary PROTACs.

Catalytic asymmetric dipolar cycloadditions of indolyl delocalized metal-allyl species for the enantioselective synthesis of cyclopenta[b]indoles and pyrrolo[1,2-α]indoles

The development of novel synthons and efficient methods to synthesize chiral polycyclic indoles has been a hot topic in organic synthesis and medicinal chemistry owing to their broad applications in medicines,pesticides,and other functional molecules.Here,we disclosed novel indolyl substituted metal-allyl zwitterionic intermediates through the decarboxylation of conveniently available vinyl indoloxazolidones,which could be regarded as two types of dipolar species through the anionic delocalization.The palladium-π-allyl species tended to serve as an all-carbon 1,3-dipole in the asymmetric[3+2]cycloaddition with electrondeficient alkenes,which furnished polysubstituted cyclopenta[b]indoles with high regio-and stereoselectivities.Meanwhile,the iridium-π-allyl species was recognized as an aza-1,3-dipole in asymmetric[3+2]cycloaddition with in situ generated C1 ammonium enolates,affording pyrrolo[1,2-α]indoles with high diastereo-and enantioselectivities.In addition,the dipolar cycloadditions could be easily scaled-up and several synthetic transformations of the cycloadducts were demonstrated for the rapid synthesis of diverse chiral polycyclic indoles.

Novel chiral C_2-symmetric multidentate aminophosphine ligands for use in catalytic asymmetric reduction of ketones

A series of novel chiral C_2-symmetric multidentate aminophosphine ligands have been successfully synthesized by Schiff-base condensation of bis（o-formylphenyl）phenylphosphane and easily available monoprotected（1R,2R）-diaminocyclohexane.The catalytic properties of these ligands were investigated in Ir-catalyzed asymmetric transfer hydrogenation of various aromatic ketones,giving the corresponding optical active alcohols with up to 98%conversion and good ee under mild reaction conditions.