The catalytic deuterodechlorination of aryl/heteroaryl chlorides was developed with a palladium/unsymmetrical NHC system, and the precisely controlled introduction of deuterium into a variety of aryl/heteroaryl compounds was achieved with a high level of efficiency, selectivity, and deuteration degree. This method was also successfully applied to the transformation of bioactive agents even in a gram-scale synthesis. The crystal structure analysis of Pd–NHC complexes led to the observation of Pd–arene interaction.

The copper-catalyzed enantioselective monoarylation of meso-1,2-diols by the use of diaryliodonium triflates as aryl sources has been developed. The chiral copper(II) complex catalyzed the asymmetric desymmetrization effectively to afford optically active β-aryloxy alcohols in moderate to high chemical yields and enantioselectivity.(R,R)-(+)-2,2′-(Nonane-5,5-diyl)bis(4-phenyl-2-oxazoline)C27H34N2O2[α]D27 = +69.1 (c 0.64, CH2Cl2)Source of chirality: amino acidAbsolute configuration: (R,R)(1S,2R)-(−)-2-PhenoxycycloheptanolC13H18O2Ee: 59%[α]D26 = −8.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)(1S,2R)-(−)-2-PhenoxycyclohexanolC12H16O2Ee: 24%[α]D25 = −9.6 (c 0.75, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)(2S,3R)-(−)-3-Phenoxybutan-2-olC10H14O2Ee: 37%[α]D27 = −11.2 (c 1.23, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

The heterocycle-containing diarylmethane synthesis from chloromethyl(hetero)arenes with (hetero)arylboron reagents was attained using the palladium/ether-imidazolium chloride system. This coupling process tolerated a diverse range of heteroaromatic moieties with sufficient catalytic activity to achieve the efficient synthesis of various diheteroarylmethanes in good to excellent yields.

Easily accessible and handled ether-imidazolium chlorides were developed as ligand precursors. The coupling reactions of heteroaryl chlorides with aryl/heteroarylboronic acids and esters were catalyzed by the palladium/ether-imidazolium chloride system with high substrate tolerance to give various heterobiaryls in good to excellent yields.

Dimethyltin(IV)dichloride-catalyzed selective oxidation of 1,2-diols in water was achieved using dibromoisocyanuric acid (DBI) or Br2 as oxidants. The catalyst activates the 1,2-diol moiety through the formation of stannylene acetal in addition to enhancing selectivity. Various cyclic and acyclic 1,2-diol substrates have been selectively oxidized affording α-hydroxyketones in good to excellent yields. This method is safe and simple in operation.

A highly diastereoselective synthesis of 2,3-disubstituted piperidines has been accomplished through nucleophilic additions to N-acyliminium ions with aryl- and alkenyl boronic acids. A reversal of stereoselectivity depending on a β-substituent on the piperidine ring was observed in the alkenylation reactions with (E)-styrylboronic acid. Our strategy was applied in the key step for the synthesis of the neurokinin NK1 receptor antagonist (±)-L-733,060.

The selective monosilylation of 1,2-diols catalyzed by dimethyltin dichloride was successfully developed. This procedure was applied to various 1,2-diols, giving monosilylated products in good to excellent yields with high chemoselectivity.

Kinetic resolution of β-hydroxyalkanephosphonates was efficiently performed by 2-fluorobenzoylation in the presence of copper(II) triflate and (R,R)-Ph-BOX as a catalyst with good s value of up to 21.Dimethyl (R)-(2-hydroxy-2-phenylethyl)phosphonateC10H15O4PEe = 49%[α]D20=-14.5 (c 1.3, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-(2-benzoyloxy-2-phenylethyl)phosphonateC17H19O5PEe = 62%[α]D20=-10.6 (c 0.53, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-[2-phenyl-2-(2-toluoyloxy)ethyl]phosphonateC18H21O5PEe = 69%[α]D20=+3.7 (c 1.1, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-[2-(2-methoxybenzoyloxy)-2-phenylethyl]phosphonateC18H21O6PEe = 6%[α]D20=-0.15 (c 1.4, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-[2-(2-fluorobenzoyloxy)-2-phenylethyl]phosphonateC17H18FO5PEe = 80%[α]D20=-6.5 (c 0.69, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-[2-(3-fluorobenzoyloxy)-2-phenylethyl]phosphonateC17H18FO5PEe = 59%[α]D20=-7.9 (c 0.70, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-[2-(4-fluorobenzoyloxy)-2-phenylethyl]phosphonateC17H18FO5PEe = 52%[α]D20=-6.6 (c 1.1, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-[2-(2,6-difluorobenzoyloxy)-2-phenylethyl]phosphonateC17H17F2O5PEe = 56%[α]D20=+7.1 (c 1.2, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-(2-pentafluorobenzoyloxy-2-phenylethyl)phosphonateC17H14F5O5PEe = 47%[α]D20=+3.4 (c 0.96, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-[2-(2-chlorobenzoyloxy)-2-phenylethyl]phosphonateC17H18ClO5PEe = 72%[α]D20=+4.1 (c 1.3, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-[2-(2-bromobenzoyloxy)-2-phenylethyl]phosphonateC17H18BrO5PEe = 61%[α]D20=-6.2 (c 1.2, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-[2-(1-naphthoyloxy)-2-phenylethyl]phosphonateC21H21O5PEe = 64%[α]D20=+28.7 (c 0.40, acetone)Source of chirality: catalytic kinetic resolutionDimethyl (S)-[2-(2-naphthoyloxy)-2-phenylethyl]phosphonateC21H21O5PEe = 55%[α]D20=-37.3 (c 0.51, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-(2-acetoxy-2-phenylethyl)phosphonateC12H17O5PEe = 16%[α]D20=+2.6 (c 1.0, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-(2-chloroacetoxy-2-phenylethyl)phosphonateC12H16ClO5PEe = 8%[α]D20=+4.7 (c 0.93, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-(2-phenyl-2-phenylaminocarbonyloxyethyl)phosphonateC17H20NO5PEe = 29%[α]D20=-6.7 (c 1.2, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Diethyl (R)-(2-hydroxy-2-phenylethyl)phosphonateC12H19O4PEe = 41%[α]D20=-10.8 (c 1.1, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Diethyl (S)-(2-benzoyloxy-2-phenylethyl)phosphonateC19H23O5PEe = 66%[α]D20=-7.8 (c 1.0, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Diethyl (S)-[2-(2-fluorobenzoyloxy)-2-phenylethyl]phosphonateC19H22FO5PEe = 83%[α]D20=+2.0 (c 1.2, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Diisopropyl (R)-(2-hydroxy-2-phenylethyl)phosphonateC14H23O4PEe = 36%[α]D20=-10.1 (c 1.4, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Diisopropyl (S)-(2-benzoyloxy-2-phenylethyl)phosphonateC21H27O5PEe = 66%[α]D20=-11.6 (c 1.4, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Diisopropyl (S)-[2-(2-fluorobenzoyloxy)-2-phenylethyl]phosphonateC21H26FO5PEe = 77%[α]D20=+2.9 (c 1.1, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dibutyl (R)-(2-hydroxy-2-phenylethyl)phosphonateC16H27O4PEe = 20%[α]D20=-11.7 (c 1.2, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dibutyl (S)-(2-benzoyloxy-2-phenylethyl)phosphonateC23H31O5PEe = 56%[α]D20=-7.8 (c 1.1, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dibutyl (S)-[2-(2-fluorobenzoyloxy)-2-phenylethyl]phosphonateC23H30FO5PEe = 82%[α]D20=-2.7 (c 1.1, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-[2-hydroxy-2-(2-methylphenyl)ethyl]phosphonateC11H17O4PEe = 34%[α]D20=-18.8 (c 1.4, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(2-fluorobenzoyloxy)-2-(2-methylphenyl)ethyl]phosphonateC18H20FO5PEe = 87%[α]D20=-27.0 (c 0.83, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-[2-hydroxy-2-(3-methylphenyl)ethyl]phosphonateC11H17O4PEe = 31%[α]D20=-11.3 (c 1.2, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(2-fluorobenzoyloxy)-2-(3-methylphenyl)ethyl]phosphonateC18H20FO5PEe = 83%[α]D20=+9.2 (c 1.4, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-[2-hydroxy-2-(4-methylphenyl)ethyl]phosphonateC11H17O4PEe = 38%[α]D20=-12.5 (c 1.3, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(2-fluorobenzoyloxy)-2-(4-methylphenyl)ethyl]phosphonateC18H20FO5PEe = 75%[α]D20=+2.8 (c 1.3, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-[2-hydroxy-2-(2-methoxyphenyl)ethyl]phosphonateC11H17O5PEe = 38%[α]D20=-20.4 (c 3.5, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(2-fluorobenzoyloxy)-2-(2-methoxyphenyl)ethyl]phosphonateC18H20FO6PEe = 74%[α]D20=-17.4 (c 1.4, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-[2-hydroxy-2-(4-methoxyphenyl)ethyl]phosphonateC11H17O5PEe = 29%[α]D20=-7.1 (c 3.8, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(2-fluorobenzoyloxy)-2-(4-methoxyphenyl)ethyl]phosphonateC18H20FO6PEe = 84%[α]D20=+1.7 (c 1.4, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-[2-hydroxy-2-(4-nitrophenyl)ethyl]phosphonateC10H14NO6PEe = 29%[α]D20=-7.6 (c 1.0, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(2-fluorobenzoyloxy)-2-(4-nitrophenyl)ethyl]phosphonateC17H17FNO7PEe = 57%[α]D20=-2.3 (c 1.3, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-[2-hydroxy-2-(4-fluorophenyl)ethyl]phosphonateC10H14FO4PEe = 41%[α]D20=-12.3 (c 1.0, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(2-fluorobenzoyloxy)-2-(4-fluorophenyl)ethyl]phosphonateC17H17F2O5PEe = 72%[α]D20=+2.1 (c 2.4, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-[2-hydroxy-2-(4-chlorophenyl)ethyl]phosphonateC10H14ClO4PEe = 37%[α]D20=-9.2 (c 1.8, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(4-chlorophenyl)-2-(2-fluorobenzoyloxy)ethyl]phosphonateC17H17ClFO5PEe = 66%[α]D20=-9.0 (c 1.2, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-[2-hydroxy-2-(4-bromophenyl)ethyl]phosphonateC10H14BrO4PEe = 49%[α]D20=-11.5 (c 0.68, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(4-bromophenyl)-2-(2-fluorobenzoyloxy)ethyl]phosphonateC17H17BrFO5PEe = 60%[α]D20=-9.6 (c 1.3, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-[2-hydroxy-2-(1-naphthyl)ethyl]phosphonateC14H17O4PEe = 43%[α]D20=-27.6 (c 2.6, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(2-fluorobenzoyloxy)-2-(1-naphthyl)ethyl]phosphonateC21H20FO5PEe = 79%[α]D20=-60.0 (c 2.2, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-[2-hydroxy-2-(2-naphthyl)ethyl]phosphonateC14H17O4PEe = 47%[α]D20=-14.3 (c 1.0, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(2-fluorobenzoyloxy)-2-(2-naphthyl)ethyl]phosphonateC21H20FO5PEe = 72%[α]D20=-24.6 (c 1.2, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-(2-hydroxypropyl)phosphonateC5H13O4PEe = 10%[α]D20=-1.4 (c 0.46, CHCl3)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (S)-[2-(2-fluorobenzoyloxy)propyl]phosphonateC12H16FO5PEe = 57%[α]D20=+15.2 (c 1.0, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (E)-(R)-(2-hydroxy-4-phenylbut-3-enyl)phosphonateC12H17O4PEe = 38%[α]D20=+3.0 (c 1.2, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Dimethyl (E)-(S)-[2-(2-fluorobenzoyloxy)-4-phenylbut-3-enyl]phosphonateC19H20FO5PEe = 58%[α]D20=-13.3 (c 0.80, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (R)-(2-hydroxy-4-phenylbut-3-ynyl)phosphonateC12H15O4PEe = 50%[α]D20=+3.4 (c 0.99, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Dimethyl (S)-[2-(2-fluorobenzoyloxy)-4-phenylbut-3-ynyl]phosphonateC19H18FO5PEe = 47%[α]D20=+4.6 (c 0.59, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Diethyl (R)-[2-hydroxy-2-(2-methylphenyl)ethyl]phosphonateC13H21O4PEe = 60%[α]D20=-25.8 (c 0.91, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Diethyl (S)-[2-(2-fluorobenzoyloxy)-2-(2-methylphenyl)ethyl]phosphonateC20H24FO5PEe = 78%[α]D20=-24.1 (c 1.1, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Diethyl (R)-[2-hydroxy-2-(4-methoxyphenyl)ethyl]phosphonateC13H21O5PEe = 59%[α]D20=-12.4 (c 1.6, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Diethyl (S)-[2-(2-fluorobenzoyloxy)-2-(4-methoxyphenyl)ethyl]phosphonateC20H24FO6PEe = 77%[α]D20=+0.95 (c 0.96, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Diethyl (R)-[2-hydroxy-2-(1-naphthyl)ethyl]phosphonateC16H21O4PEe = 47%[α]D20=-31.5 (c 0.76, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Diethyl (S)-[2-(2-fluorobenzoyloxy)-2-(1-naphthyl)ethyl]phosphonateC23H24FO5PEe = 61%[α]D20=-44.9 (c 1.0, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)Diethyl (R)-(2-hydroxypropyl)phosphonateC7H17O4PEe = 49%[α]D20=-5.2 (c 0.87, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (R)Diethyl (S)-[2-(2-fluorobenzoyloxy)propyl]phosphonateC14H20FO5PEe = 56%[α]D20=+15.1 (c 1.0, acetone)Source of chirality: catalytic kinetic resolutionAbsolute configuration: (S)

A facile synthetic method toward optically active 3,3-disubstituted oxindoles with excellent enantioselectivity was achieved using chiral copper-catalyzed desymmetrization of prochiral 1,3-diols. The monotosylated product was transformed into oxindole derivatives efficiently.(R)-(+)-3-Hydroxymethyl-1-methyl-3-(p-toluenesulfonyloxymethyl)oxindoleC18H19O5NS[α]D22=+17.2 (c 1.0, CHCl3)Source of chirality: catalytic asymmetric monotosylationAbsolute configuration: (R)(R)-(+)-3-Benzyloxymethyl-3-cyanomethyl-1-methyloxindoleC19H18N2O2[α]D22=+16.7 (c 0.36, CH2Cl2)Source of chirality: catalytic asymmetric monotosylationAbsolute configuration: (R)(R)-(+)-3-((+)-10-Camphorsulfonyloxymethyl)-1-methyl-3-(p-toluenesulfonyloxymethyl)oxindoleC28H33O8NS2[α]D22=+24.0 (c 0.5, CHCl3)Source of chirality: catalytic asymmetric monotosylationAbsolute configuration: (R)

α-Cyanation of N-protected cyclic amines was achieved using a direct electrochemical method. Unsubstituted N-protected cyclic amines were easily cyanated at the α-position using an undivided cell in high yields; moreover, α-cyanation of α′-substituted pyrrolidine and α′-,β′- or γ-substituted piperidines smoothly proceeded in high yield and with high to excellent diastereoselectivity. α-Substituted N-cyano-pyrrolidines and -piperidines were also cyanated at the more substituted position (the α-position) using a divided cell with high yield and high regioselectivity.

An enantiomerically pure bicyclic proline derivative was prepared by cis-selective allylation and diastereospecific intramolecular alkylation starting from d-pipecolinic acid. In addition, enantiomerically pure azabicyclo N-oxyls derived from the bicyclic proline worked well as catalysts for the enantioselective electrooxidation of racemic sec-alcohols to afford optically active sec-alcohols in moderate enantiomeric purity.Methyl N-methoxycarbonyl-(6S)-allyl-d-pipecolinateC12H19NO4[α]D20=+106.6 (c 1.0, CHCl3)Absolute configuration: (6S)Source of chirality: d-pipecolinic acidMethyl N-methoxycarbonyl-(6S)-(2-hydroxyethyl)-d-pipecolinateC11H19NO5[α]D20=+50.2 (c 1.0, CHCl3)Absolute configuration: (6S)Source of chirality: d-pipecolinic acidMethyl N-methoxycarbonyl-(6S)-[2-(p-tolunesulfonyloxy)ethyl]-d-pipecolinateC18H25NO7S[α]D20=+61.5 (c 1.0, CHCl3)Absolute configuration: (6S)Source of chirality: d-pipecolinic acidMethyl (1R)-N-methoxycarbonyl-8-azabicyclo[3.2.1]octane-1-carboxylateC11H17NO4Ee = >99%[α]D23=+25.0 (c 1.0, CHCl3)Absolute configuration: (1S)Source of chirality: d-pipecolinic acid(1R)-N-Methoxycarbonyl-8-azabicyclo[3.2.1]octane-1-carboxylic acidC10H15NO4Ee = >99%[α]D29=+21.6 (c 1.0, CHCl3)Absolute configuration: (1S)Source of chirality: d-pipecolinic acidMethyl N-[(1R)-N-methoxycarbonyl-8-azabicyclo[3.2.1]octane-1-carbonyl]dimethylglycyl-dimethylglycinateC19H31N3O6[α]D25=+25.6 (c 0.5, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acidMethyl (1R)-8-azabicyclo[3.2.1]octane-1-carboxylateC9H15NO2Ee = >99%[α]D28=+14.3 (c 0.7, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acidMethyl (1R)-8-azabicyclo[3.2.1]octane-1-carboxylate-N-oxylC9H13NO3Ee = >99%[α]D29=-13.9 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid(1R)-N-Methoxycarbonyl-1-hydroxylmethyl-8-azabicyclo[3.2.1]octaneC10H17NO3Ee = >99%[α]D26=-21.3 (c 0.9, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid(1R)-N-Methoxycarbonyl-1-benzoyloxymethyl-8-azabicyclo[3.2.1]octaneC17H21NO4Ee = >99%[α]D25=+51.3 (c 1.2, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid(1R)-Benzoyloxymethyl-8-azabicyclo[3.2.1]octaneC15H19NO2Ee = >99%[α]D25=+1.4 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid(1R)-Benzoyloxymethyl-8-azabicyclo[3.2.1]octane-N-oxylC15H18NO3Ee = >99%[α]D24=+48.8 (c 1.0, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid(1R)-N-Methoxycarbonyl-1-N-phenylcarbamoyl-8-azabicyclo[3.2.1]octaneC16H20N2O3Ee = >99%[α]D18=+71.6 (c 1.0, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid(1R)-N-Methoxycarbonyl-1-N-benzylcarbamoyl-8-azabicyclo[3.2.1]octaneC17H22N2O3Ee = >99%[α]D25=+70.8 (c 1.0, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acidMethyl N-[(1R)-N-Methoxycarbonyl-8-azabicyclo[3.2.1]octane-1-carbonyl]-l-phenylglycinateC19H24N2O5Ee = >99%[α]D25=+53.0 (c 0.9, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acidMethyl N-[(1R)-N-Methoxycarbonyl-8-azabicyclo[3.2.1]octane-1-carbonyl]-d-phenylglycinateC19H24N2O5Ee = >99%[α]D25=+74.7 (c 0.9, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid(1R)-N-Phenylcarbamoyl-8-azabicyclo[3.2.1]octaneC14H18N2OEe = >99%[α]D27=+74.6 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid(1R)-N-Benzylcarbamoyl-8-azabicyclo[3.2.1]octaneC15H20N2OEe = >99%[α]D28=+28.2 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acidMethyl N-[(1R)-8-azabicyclo[3.2.1]octane-1-carbonyl]-l-phenylglycinateC17H22N2O3Ee = >99%[α]D24=+0.8 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acidMethyl N-[(1R)-8-azabicyclo[3.2.1]octane-1-carbonyl]-d-phenylglycinateC17H22N2O3Ee = >99%[α]D25=+1.4 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid(1R)-N-Phenylcarbamoyl-8-azabicyclo[3.2.1]octane-N-oxylC14H17N2O2Ee = >99%[α]D29=+72.1 (c 0.9, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid(1R)-N-Benzylcarbamoyl-8-azabicyclo[3.2.1]octane-N-oxylC15H19N2O2Ee = >99%[α]D29=+18.7 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acidMethyl N-[(1R)-8-azabicyclo[3.2.1]octane-1-carbonyl]-l-phenylglycinate-N-oxylC17H21N2O4Ee = 99%[α]D25=+86.1 (c 0.8, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acidMethyl N-[(1R)-8-azabicyclo[3.2.1]octane-1-carbonyl]-d-phenylglycinate-N-oxylC17H21N2O4Ee = >99%[α]D25=+119.7 (c 1.3, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

α-Cyanation of N-protected cyclic amines was achieved using a direct electrochemical method. Unsubstituted N-protected cyclic amines were easily cyanated at the α-position using an undivided cell in high yields; moreover, α-cyanation of α′-substituted pyrrolidine and α′-,β′- or γ-substituted piperidines smoothly proceeded in high yield and with high to excellent diastereoselectivity. α-Substituted N-cyano-pyrrolidines and -piperidines were also cyanated at the more substituted position (the α-position) using a divided cell with high yield and high regioselectivity.