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 crucial for simultaneous activation and thioamides, affording the beta-alkynylthioamides in a highly enantioselective manner. Control experiments suggested that intermediate copper thioamide enolate can work as drive cycle via transfer. The divergent transformation functionality...

A direct catalytic asymmetric addition of allyl cyanide to ketones with a bimetallic system comprising (R,R)-Ph-BPE/[Cu(CH3CN)4]ClO4/LiOAr is described. Exclusive γ-addition was observed, affording optically enriched tertiary alcohols bearing Z-configured α,β-unsaturated nitriles. The reaction proceeded under proton-transfer conditions, utilizing soft Lewis acid/hard Brønsted base bifunctional catalysis. applicability the aromatic, heteroaromatic, and aliphatic demonstrates its wide...

We report that a hard Lewis base substantially affects the reaction efficiency of direct catalytic asymmetric γ-addition allyl cyanide (1a) to ketones promoted by soft acid/hard Brønsted catalyst. Mechanistic studies have revealed Cu/(R,R)-Ph-BPE and Li(OC6H4-p-OMe) serve as acid base, respectively, allowing for deprotonative activation 1a rate-determining step. A ternary system comprising an additional in which basicity was enhanced phosphine oxide (the base) through hard−hard interaction,...

A direct catalytic asymmetric aldol reaction of thioamides using a soft Lewis acid/hard Brønsted base cooperative catalyst comprising (R,R)-Ph-BPE/[Cu(CH3CN)4]PF6/LiOAr is described. Exclusive enolate generation from thioacetamides through soft−soft interaction with the acid allowed for to α-nonbranched aliphatic aldehydes, which are usually susceptible self-condensation under conventional basic conditions. hard phosphine oxide has emerged as an effective additive constitute highly active...

A direct copper-catalyzed highly chemoselective α-amination is described. Acylpyrazole proved to be a efficient enolate precursor of carboxylic acid oxidation state substrate, while preactivation by stoichiometric amount strong base has been used in catalytic α-aminations. The simultaneous activation both coupling partners, enolization and metal nitrenoid formation, was crucial for obtaining the product, wide functional group compatibility highlighted mildness present catalysis. bidentate...

Unnatural α-amino acids are invaluable building blocks in synthetic organic chemistry and could upgrade the function of peptides. We developed a new mode for catalytic activation amino acid Schiff bases, serving as platform highly congested unnatural synthesis. The redox active copper catalyst enabled efficient cross-coupling to construct contiguous tetrasubstituted carbon centers. broad functional group compatibility highlights mildness present catalysis. Notably, we achieved successive...

Direct catalytic asymmetric addition of allylic cyanides to N-diphenylphosphinoyl ketoimines with a bimetallic system comprising Ph-BPE/[Cu(CH3CN)4]ClO4/LiOAr is described. Intermediary alpha-adducts readily isomerized afford synthetically useful alpha,beta-unsaturated nitriles bearing an optically active tetrasubstituted carbon. Applicability aromatic, heteroaromatic, and aliphatic exemplifies wide substrate generality. Transformation the product into densely functionalized material...

A direct catalytic asymmetric aldol reaction of thioamides with a soft Lewis acid/hard Brønsted base cooperative system comprising (R,R)-Ph-BPE/[Cu(CH(3)CN)(4)]PF(6)/LiOAr is described. Highly chemoselective deprotonative activation allows for alpha-nonbranched aliphatic aldehydes, which are susceptible to self-condensation. Facile reduction the thioamide functionality and catalyst-controlled second provides 1,3-diols in highly stereoselective manner.

A synthetic route to trans-configured tetrahydrothiophenes (THTs) through Fe(OTf)3 -promoted [3+2] cycloaddition of donor-acceptor cyclopropanes with thionoesters was developed. The proceeded in high yield diastereoselectivity, affording transient α-alkoxy THTs. Not only aromatic and aliphatic thionoesters, but also thionolactone were applicable the present iron catalysis. Further transformation S,O-ketal functionality product achieved a highly trans diastereoselective manner. Moreover,...

Much more reactive than the corresponding benzophenone imines, which have often been used in synthesis of α-amino acids, title compounds undergo Mannich-type reactions with imines presence a catalytic amount base to afford α,β-diamino acid and α,β-diaminophosphonic derivatives high syn diastereoselectivity (see scheme). An asymmetric version reaction is also described. Boc=tert-butoxycarbonyl. Glycine are useful starting materials for acids. For example, glycine esters, type 1 introduced by...

Twice the catalyst: The simultaneous activation of an allyl cyanide (pronucleophile) and α,β-unsaturated thioamide (electrophile) was achieved using a Cu-based soft Lewis acid/hard Brønsted base cooperative catalyst, thus resulting in formation enethioamides 1 highly enantio- Z-selective manner (see scheme). sequential Cu-catalyzed intramolecular cyclization gave rise to enantioenriched fused isothiazoles 2. Detailed facts importance specialist readers are published as "Supporting...

The synthesis of novel oxetanyl peptides, where the amide bond is replaced by a non-hydrolyzable oxetanylamine fragment, reported. This new class pseudo-dipeptides with same H-bond donor/acceptor pattern found in proteins expands repertoire peptidomimetics.

Chemoselective iron-catalyzed dehydrogenative cross-coupling using 2-acylimidazoles is described. The addition of a phosphine oxide ligand substantially facilitated the generation tert-butoxy radicals from di-tert-butyl peroxide, allowing for efficient benzylic C–H bond cleavage under mild conditions. Extensive mechanistic studies revealed that enolization 2-acylimidazole proceeded through dual iron catalyst activation, followed by subsequent chemoselective with benzyl radical over an...

We developed a chemoselective catalytic activation of carboxylic acid for 1e– radical process. α-Oxidation variety acids, which preferentially undergo undesired decarboxylation under conditions, proceeded efficiently the optimized conditions. Chemoselective enolization was also achieved even in presence more acidic carbonyls. Extensive mechanistic studies revealed that cooperative actions iron species and alkali metal ions derived from 4 Å molecular sieves substantially facilitated...

Abstract Taking the reins : The title transformation of thioamides and N ‐diphenylphosphinoyl imines is described. By harnessing power cooperative catalysis between a soft Lewis acid hard Brønsted base, thioamide carbon pronucleophiles can furnish Mannich products (see scheme). Divergent functionality highlights utility this methodology. magnified image

Abstract A detailed study of the direct catalytic asymmetric conjugate addition terminal alkynes to α,β‐unsaturated thioamides is described. soft Lewis acid/hard Brønsted base cooperative catalyst, comprising [Cu(CH 3 CN) 4 ]PF 6 , bisphosphine ligand, and Li(OC H ‐ p ‐OMe) simultaneously activated both substrates compensate for low reactivity copper alkynylide. series control experiments revealed that intermediate copper‐thioamide enolate functioned as a generate alkynylide from alkyne,...

We designed highly active and practical bis(imidazole)/zinc complexes for transesterification reactions.

A new strategy, a transient homocoupling dimer for direct catalytic oxidative cross-enolate coupling reactions is developed. Cross-enolate products bearing (contiguous) tetrasubstituted carbon center were obtained chemoselectively without the need stoichiometric amounts of strong bases/metal oxidants, and thus, present catalysis provides general method synthesis unnatural α,α-disubstituted amino acid motifs. The distinct transformation azlactone 2-acylimidazole units highlighted synthetic...

We developed a catalytic aerobic method to synthesize α,α-disubstituted α-amino acids through cross-dehydrogenative coupling of azlactones. Combining an iron catalyst with bisoxazolidine ligand resulted in high performance, and cross-coupling indole proceeded smoothly under conditions. A wide variety α-aryl aliphatic amino acid derived azlactones were applied the present catalysis. In addition, quaternary carbon could be constructed using oxindole benzofuranone

A concise enantioselective synthetic route to a potent GPR40 agonist AMG 837 is described. The crucial catalytic asymmetric conjugate addition of terminal alkyne was promoted by soft Lewis acid/hard Brønsted base cooperative catalyst, allowing efficient construction the requisite stereogenic center. thioamide functional group key both activation in alkynylation and facile transformation into carboxylic acid.

Direct catalytic asymmetric aldol reaction of thioamide offers a new entry to the concise enantioselective synthesis duloxetine. The direct protocol was scalable (>20 g) afford product in 92% ee after LiAlH(4) reduction, and 84% chiral ligand recovered recrystallization. following four steps transformation delivered

Abstract A highly chemoselective conjugate addition of alcohols in the presence amines is described. The cooperative nature catalyst enabled activation over amines, allowing to soft Lewis basic α,β‐unsaturated nitriles. Divergent transformation nitrile functionality highlights utility present catalysis.