Synlett, Table of Contents Synlett 2019; 30(11): 1356-1360DOI: 10.1055/s-0037-1611842 letter © Georg Thieme Verlag Stuttgart · New YorkAsymmetric Mannich Reaction of N-Boc Imines with Alkylmalononitriles Catalyzed by Dinuclear PhosphoiminoBINOL-Pd Complex Takayoshi Arai * a Soft Molecular Activation Research Center (SMARC), Chiba University1-33 Yayoi, Inage, Chiba 263-8522, Japan b Chiba Iodine Research Innovation Center (CIRIC), Chiba University1-33 Yayoi, Inage, Chiba 263-8522, Japan c Department of Chemistry, Graduate School of Science, Chiba University1-33 Yayoi, Inage, Chiba 263-8522, Japan Email: tarai@faculty.chiba-u.jp , Ayu Nakamura a Soft Molecular Activation Research Center (SMARC), Chiba University1-33 Yayoi, Inage, Chiba 263-8522, Japan b Chiba Iodine Research Innovation Center (CIRIC), Chiba University1-33 Yayoi, Inage, Chiba 263-8522, Japan c Department of Chemistry, Graduate School of Science, Chiba University1-33 Yayoi, Inage, Chiba 263-8522, Japan Email: tarai@faculty.chiba-u.jp› Author AffiliationsRecommend Article Abstract Buy Article All articles of this category Abstract PhosphoiminoBINOL-Pd2(OAc)2 complex catalyzed asymmetric Mannich reaction of N-Boc imines with alkyl malononitriles, with assistance of Zn(OAc)2 gave chiral amines with adjacent all-carbon quaternary carbon centers in up to 99% yield with 94% ee. Key words Key wordsMannich - asymmetric catalyst - chiral amine - quaternary carbon center Full Text References References and Notes Reviews of catalytic asymmetric Mannich reaction: 1a Cordova A. Acc. Chem. Res. 2004; 37: 102 1b Cai X.-H, Hui G, Bing X. Eur. J. Chem. 2012; 3: 258 1c Kumagai N, Shibasaki M. Bull. Chem. Soc. Jpn. 2015; 88: 503 1d Saranya S, Harry NA, Krishnan KK, Anilkumar G. Asian J. Org. Chem. 2018; 7: 613 Selected examples of asymmetric catalyses using malononitrile: 2a Taylor MS, Jacobsen EN. J. Am. Chem. Soc. 2003; 125: 11204 2b Kanemasa S, Itoh K. Eur. J. Org. Chem. 2004; 4741 2c Hoashi Y, Okino T, Takemoto Y. Angew. Chem. Int. Ed. 2005; 44: 4032 2d Inokuma T, Hoashi Y, Takemoto Y. J. Am. Chem. Soc. 2006; 128: 9413 2e Wang J, Li H, Zu L, Jiang W, Xie H, Duan W, Wang W. J. Am. Chem. Soc. 2006; 128: 12652 2f Li XF, Cun LF, Lian CX, Zhang L, Chen YC, Liao J, Zhu J, Deng JG. Org. Biomol. Chem. 2008; 6: 349 2g Russo A, Perfetto A, Lattanzi A. Adv. Synth. Catal. 2009; 351: 3067 2h Gogoi S, Zhao C.-G. Tetrahedron Lett. 2009; 50: 2252 2i Jing LH, Wei JT, Zhou L, Huang ZY, Li ZK, Wu D, Xiang HF, Zhou XG. Chem. Eur. J. 2010; 16: 10955 2j Ren Q, Gao YJ, Wang J. Chem. Eur. J. 2010; 16: 13594 2k Su Z, Lee HW, Kim CK. Org. Biomol. Chem. 2011; 9: 6402 2l Tan HR, Ng HF, Chang J, Wang J. Chem. Eur. J. 2012; 18: 3865 2m Su Z, Lee HW, Kim CK. Eur. J. Org. Chem. 2013; 1706 2n Gao Y, Du D.-M. Chem. Asian J. 2014; 9: 2970 2o Fu N, Zhang L, Luo S. Org. Lett. 2015; 17: 382 2p Caruana L, Mondatori M, Corti V, Morales S, Mazzanti A, Fochi M, Bernardi L. Chemistry 2015; 21: 6037 2q Wang Y, Xu Y.-N, Fang G.-S, Kang H.-J, Gu Y, Tian S.-K. Org. Biomol. Chem. 2015; 13: 5367 2r Brindani N, Dell’Amico L, Curti C, Sartori A, Battistini L, Casiraghi G, Greco D, Zanardi F, Brindani N, Rassu G. Angew. Chem. Int. Ed. 2015; 54: 7386 2s Zhu Q.-N, Zhang Y.-C, Xu M.-M, Sun X.-X, Yang X, Shi F. J. Org. Chem. 2016; 81: 7898 2t Zheng S.-C, Wu S, Zhou Q, Chung LW, Ye L, Tan B. Nat. Commun. 2017; 815238 2u Grugel CP, Breit B. Chemistry 2018; 24: 15223 2v Chen X.-Y, Li S, Liu Q, Kumar M, Peuronen A, Rissanen K, Enders D. Chem. Eur. J. 2018; 24: 9735 2w Grugel CP, Breit B. Chem. Eur. J. 2018; 24: 15223 2x Hayashi Y, Kranidiotis-Hisatomi N, Sakamoto D, Oritani K, Kawamoto T, Kamimura A. Eur. J. Org. Chem. 2018; 6843 2y Zhang Y.-C, Zhang B.-W, Geng R.-L, Song J. Org. Lett. 2018; 20: 7907 2z Liu X, Wang K, Guo W, Liu Y, Li C. Chem. Commun. 2019; 55: 2668 3 Lu Z, Xie C, Zhou W, Duan Z, Han J, Pan Y. Chin. J. Chem. 2012; 30: 2333 4 Monge D, Jensen KL, Franke PT, Lykke L, Jørgensen KA. Chem. Eur. J. 2010; 16: 9478 5 Chen X, Chen H, Ji X, Jiang H, Yao Z.-J, Liu H. Org. Lett. 2013; 15: 1846 Other selected examples for asymmetric Mannich reaction using alkyl malononitriles: 6a Ding R, De los Santos ZA, Wolf C. ACS Catal. 2019; 9: 2169 6b Kawato Y, Kumagai N, Shibasaki M. Chem. Commun. 2013; 49: 11227 6c Lin S, Kawato Y, Kumagai N, Shibasaki M. Angew. Chem. Int. Ed. 2015; 54: 5183 6d Hashimoto K, Kumagai N, Shibasaki M. Chem. Eur. J. 2015; 21: 4262 6e Xu L, Wang H, Zheng C, Zhao G. Adv. Syn. Catal. 2017; 359: 2942 6f Balaji PV, Brewitz L, Kumagai N, Shibasaki M. Angew. Chem. Int. Ed. 2018; 58: 2644 6g Nakashima K, Noda Y, Hirashima S, Koseki Y, Miura T. J. Org. Chem. 2018; 83: 2402 7a Arai T, Oka I, Morihata T, Awata A, Masu H. Chem. Eur. J. 2013; 19: 1554 7b Arai T, Moribatake T, Masu H. Chem. Eur. J. 2015; 21: 10671 7c Arai T, Tosaka T, Kuwano S. ChemistrySelect 2017; 2: 7368 7d Kuwano S, Suzuki T, Hosaka Y, Arai T. Chem. Commun. 2018; 54: 3847 8 Arai T, Sato K, Nakamura A, Makino H, Masu H. Sci. Rep. 2018; 8: 837 9 Typical Experimental Procedures A mixture of 3,3′-bis(phosphoimino)binaphthol (0.005 mmol) and Pd(OAc)2 (0.01 mmol) was stirred in anhydrous chloroform (4.0 mL) for 12 h at 60 °C. After adding Zn(OAc)2 (0.005 mmol) to the mixture, the solution was further stirred for 12 h at 60 °C to give the catalyst solution. The Mannich reaction was started by adding alkyl malononitrile (0.1 mmol) and N-Boc aldimine (0.11 mmol) to the catalyst solution at rt. After being stirred for 4 h at rt, the reaction mixture was quenched with H2O, and then the products were extracted three times with dichloromethane. The collected organic layer was dried over Na2SO4. After removal of the solvent under reduced pressure, the residue was purified by a silica gel column chromatography. The enantiomeric excesses of the products were determined by chiral stationary phase HPLC using Daicel Chiralpak IA or AD-H column. 10 Characterization Data of 3aa [α]D 20.4 +30.5° (c 1.0, CHCl3, 93% ee). 1H NMR (400 MHz, CDCl3): δ = 7.51–7.45 (m, 5 H), 7.41–7.38 (m, 5 H), 5.54 (d, J = 9.6 Hz, 1 H), 5.32 (d, J = 9.6 Hz, 1 H), 3.27 (d, J = 14.0 Hz, 1 H), 3.17 (d, J = 13.6 Hz, 1 H), 1.47 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 154.8, 130.1, 129.4, 128.5, 127.0, 111.1, 110.8, 81.7, 55.5, 29.6, 28.1. IR (neat): 3347, 2980, 1706, 1521, 1498, 1368, 1250, 1167, 762, 705 cm–1. HRMS (ESI+): m/z calcd for C22H24O2N3 [M + H]+: 362.1863; found: 362.1860. Enantiomeric excess was determined by HPLC with a Chiralpak IA column (hexane/2-propanol = 80:20, 1.0 mL/min, 254 nm); major enantiomer t R = 9.7 min, minor enantiomer t R = 6.0 min, 93% ee. Pd-catalyzed asymmetric amination: 11a Trost BM. Chem. Rev. 1996; 96: 395 11b Trost BM, Crawley ML. Chem. Rev. 2003; 103: 2921 11c Miyabe H, Matsumura A, Yoshida K, Yamauchi M, Takemoto Y. Synlett 2004; 2123 11d Trost BM, Machacek MR, Aponick A. Acc. Chem. Res. 2006; 39: 747 11e Lu Z, Ma S. Angew. Chem. Int. Ed. 2008; 47: 258 Supplementary Material Supplementary Material Supporting Information
