Kinetic resolution of alkyne-substituted quaternary oxindoles via copper catalysed azide-alkyne cycloadditions

Kinetic resolution of alkyne-substituted quaternary oxindoles via copper catalysed azide-alkyne cycloaddition

Asymmetric copper catalyzed azide-alkyne cycloadditions

Since its discovery independently by Sharpless and Meldal in 2002, the copper-catalyzed azide–alkyne cycloaddition (CuAAC) has become a ubiquitous molecular linking platform. Easy access to substituted 1,4-triazoles can be exploited to engender asymmetry to a myriad of potentially useful targets in high yields. Utilizing the CuAAC to form chiral triazolic products in a single step is an attractive and powerful approach for the synthetic chemist. The area of asymmetric CuAAC is still in its infancy compared to more established asymmetric metal-mediated transformations; however, this leads to exciting challenges that need to be overcome to usher in the next era in the story of the triazole and click chemistry in general. This review details the steps taken into asymmetric CuAAC and the exciting results achieved thus far. [Note that diagrams accompany this abstract in the published version and can be found at http://dx.doi.org/10.1021/acscatal.6b00996.

A Direct Route to Platinum NCN-Pincer Complexes Derived from 1,3-Bis(imino)benzenes and an Investigation into Their Activity as Catalysts for Carbon−Carbon Bond Formation

1,3-Bis(imino)lbenzenes [1,3-C6H4(CHNR)2], obtained from condensation of 1,3-isophthalaldehyde with primary amines (R = tBu, Cy, Bu, Bn, Ph), were heated with K2PtCl4 at reflux for 48 h in glacial acetic acid to give ((2,6-bis(N-R-substituted)imino)phenyl)platinum(II) chloride complexes (15−52% yield). X-ray crystal structures of the R = tBu and R = Ph complexes are reported. The byproducts were found to be 1,3-isophthalaldehyde and N-acetylamines. Quantitative chloride abstraction with AgBF4 (R = tBu) or AgOTf (R = tBu, Cy) provided the corresponding cationic complexes containing water coordinated to platinum, as established by an X-ray crystal structure of ((2,6-bis(N-tert-butyl)imino)phenyl)aquoplatinum(II) trifluoromethanesulfonate. Use of 4−5 mol % of ((2,6-bis(N-cyclohexyl)imino)phenyl)aquoplatinum(II) trifluoromethanesulfonate accelerated the rate of the Michael reaction between ethyl α-cyanoacetate and methyl vinyl ketone and the Diels−Alder reaction between acrylonitrile and cyclopentadiene

Synthesis of 2,6-Bis(2-oxazolinyl)phenylplatinum(II) NCN Pincer Complexes by Direct Cyclometalation. Catalysts for Carbon−Carbon Bond Formation

1,3-Bis(4‘,4‘-dimethyl-2‘-oxazolinyl)benzene (5a) and 5-nitro-1,3-bis(4‘,4‘-dimethyl-2‘-oxazolinyl)benzene (5b) were heated in dry acetic acid with K2PtCl4 to give the corresponding 2,6-bis(4‘,4‘-dimethyl-2‘-oxazolinyl)phenylplatinum(II) chloride complexes 6a and 6b in 49 and 11% yield, respectively. The X-ray structure of 6b is reported. The main side product observed in the platination of 5a was identified as di(2-methyl-2-N-acetyl)propyl isophthalate. In contrast, use of Pd(OAc)2 with 5a in this protocol, followed by addition of LiBr, gave 2,6-bis(4‘,4‘-dimethyl-2‘-oxazolinyl)phenylpalladium(II) bromide in only 3% yield. Treatment of 6a with AgOTf and AgSbF6 in acetone gave quantitatively the corresponding cationic 2,6-bis(4‘,4‘-dimethyl-2‘-oxazolinyl)phenyl(aquo)platinum(II) complexes 15a and 15b. Similarly treatment of 6b with AgOTf in acetone gave 4-nitro-2,6-bis(4‘,4‘-dimethyl-2‘-oxazolinyl)phenyl(aquo)platinum(II) trifluoromethanesulfonate (15c) (72%). Complexes 15a−c, together with 2,6-bis(4‘,4‘-dimethyl-2‘-oxazolinyl)phenylaquopalladium(II) triflate (15d), were applied as catalysts for the Michael reaction between methyl vinyl ketone and ethyl cyanoacetate and the Diels−Alder reaction between acrylonitrile and cyclopentadiene. In both cases platinum complex 15a was found to be the most active, with the 4-nitro group of 15c resulting in decreased catalytic activity

Diastereoselective Preparation of Azetidines and Pyrrolidines

Iodine-mediated cyclization of homoallyl amines at room temperature delivered cis-2,4-azetidine through a 4-exo trig cyclization. Isomerization of iodo-azetidines to cis-pyrrolidines could be achieved by heating, with complete stereocontrol. The relative stereochemistry of the iodo-azetidines and pyrrolidines was confirmed by NMR spectroscopy and X-ray crystallography. Further functionalization was achieved through nucleophilic displacement of iodine to deliver substituted azetidines and pyrrolidines. 1,2,3-Triazole-appended azetidines and pyrrolidines were also prepared

Diastereoselective Preparation of Azetidines and Pyrrolidines

Iodine-mediated cyclization of homoallyl amines at room temperature delivered cis-2,4-azetidine through a 4-exo trig cyclization. Isomerization of iodo-azetidines to cis-pyrrolidines could be achieved by heating, with complete stereocontrol. The relative stereochemistry of the iodo-azetidines and pyrrolidines was confirmed by NMR spectroscopy and X-ray crystallography. Further functionalization was achieved through nucleophilic displacement of iodine to deliver substituted azetidines and pyrrolidines. 1,2,3-Triazole-appended azetidines and pyrrolidines were also prepared

Diastereoselective Preparation of Azetidines and Pyrrolidines

Iodine-mediated cyclization of homoallyl amines at room temperature delivered cis-2,4-azetidine through a 4-exo trig cyclization. Isomerization of iodo-azetidines to cis-pyrrolidines could be achieved by heating, with complete stereocontrol. The relative stereochemistry of the iodo-azetidines and pyrrolidines was confirmed by NMR spectroscopy and X-ray crystallography. Further functionalization was achieved through nucleophilic displacement of iodine to deliver substituted azetidines and pyrrolidines. 1,2,3-Triazole-appended azetidines and pyrrolidines were also prepared

Asymmetric copper catalyzed azide-alkyne cycloadditions

Since its discovery independently by Sharpless and Meldal in 2002, the copper-catalyzed azide–alkyne cycloaddition (CuAAC) has become a ubiquitous molecular linking platform. Easy access to substituted 1,4-triazoles can be exploited to engender asymmetry to a myriad of potentially useful targets in high yields. Utilizing the CuAAC to form chiral triazolic products in a single step is an attractive and powerful approach for the synthetic chemist. The area of asymmetric CuAAC is still in its infancy compared to more established asymmetric metal-mediated transformations; however, this leads to exciting challenges that need to be overcome to usher in the next era in the story of the triazole and click chemistry in general. This review details the steps taken into asymmetric CuAAC and the exciting results achieved thus far. [Note that diagrams accompany this abstract in the published version and can be found at http://dx.doi.org/10.1021/acscatal.6b00996.

Heterochiral Triangulo Nickel Complex as Evidence of a Large Positive Nonlinear Effect in Catalysis

A novel triangulo complex was generated by heating, in vacuo, a racemic C2-symmetric octahedral nickel(II) diamine complex. The trinuclear species was identified by single-crystal X-ray diffraction, which revealed a 2:1 ligand stereochemistry relationship in each unit. This solid-state structure evidences the hypothesis that a 1:2 stereochemical relationship lies at the heart of the strong positive nonlinear effect observed in enecarbamate aldol-like reactions catalyzed by nickel(II) diamine complexes

Heterochiral Triangulo Nickel Complex as Evidence of a Large Positive Nonlinear Effect in Catalysis

A novel triangulo complex was generated by heating, in vacuo, a racemic C2-symmetric octahedral nickel(II) diamine complex. The trinuclear species was identified by single-crystal X-ray diffraction, which revealed a 2:1 ligand stereochemistry relationship in each unit. This solid-state structure evidences the hypothesis that a 1:2 stereochemical relationship lies at the heart of the strong positive nonlinear effect observed in enecarbamate aldol-like reactions catalyzed by nickel(II) diamine complexes