Asymmetric Synthesis of a Bicyclo[4.3.0]nonene Derivative Bearing a Quaternary Carbon Stereocenter: Desymmetrization of σ-Symmetrical Diketones through Intramolecular Addition of an Alkenyl Anion

Tomoyuki Yoshimura; Yuki Enami; Jun-ichi Matsuo

doi:10.1055/s-0040-1706421

Synthesis, Table of Contents

Synthesis 2020; 52(23): 3667-3674
DOI: 10.1055/s-0040-1706421

paper

Asymmetric Synthesis of a Bicyclo[4.3.0]nonene Derivative Bearing a Quaternary Carbon Stereocenter: Desymmetrization of σ-Symmetrical Diketones through Intramolecular Addition of an Alkenyl Anion

Tomoyuki Yoshimura ∗

Division of Pharmaceutical Sciences, Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan Email: yosimura@p.kanazawa-u.ac.jp

,

Yuki Enami

,

Jun-ichi Matsuo

› Author Affiliations

Abstract

All articles of this category

Abstract

The enantioselective synthesis of a bicyclo[4.3.0]nonene derivative bearing a quaternary carbon stereocenter is achieved by employing a desymmetrization strategy involving an intramolecular addition. The intramolecular nucleophilic addition of a highly reactive carbanion generated from an alkenyl iodide in the presence of a chiral ligand occurs with discrimination of two keto carbonyl groups to give the corresponding bicyclic compound in 81% yield and 39% ee. Asymmetric synthesis via an intramolecular desymmetrization strategy using a chiral ligand–carbanion complex represents a complementary approach to using chiral organocatalysts or chiral ligand–transition-metal complexes.

Key words

desymmetrization - asymmetric synthesis - alkenyl lithium - quaternary carbon stereocenter - bicyclo[4.3.0]nonene

Full Text

References

References

1a Li C, Ragab S, Liu G, Tang W. Nat. Prod. Rep. 2020; 37: 276
1b Xu P.-W, Yu J.-S, Chen C, Cao Z.-Y, Zhou F, Zhou J. ACS Catal. 2019; 8: 1820
1c Feng J, Holmes M, Krische MJ. Chem. Rev. 2017; 117: 12564
1d Overman LE, Quasdorf KW. Nature 2014; 516: 181

2a Zeng X.-P, Cao Z.-Y, Wang Y.-H, Zhou F, Zhou J. Chem. Rev. 2016; 116: 7330
2b Petersen KS. Tetrahedron Lett. 2015; 56: 6523
2c Studer A, Schleth F. Synlett 2005; 3033

3 Buchschacher P, Fürst A, Gutzwiller J. Org. Synth. 1985; 63: 37
4 Hajos ZG, Parrish DR. Org. Synth. 1985; 63: 26
5 Nakazaki K, Hayashi K, Hosoe S, Tashiro T, Kuse M, Takikawa H. Tetrahedron 2012; 68: 9029
6 Tang Y, Liu J, Chen P, Ly M, Wang Z, Huang Y. J. Org. Chem. 2014; 79: 11729

7a Wei Q, Cai J, Hu X.-D, Zhao J, Cong H, Zheng C, Liu W.-B. ACS Catal. 2020; 10: 216
7b Selmani A, Darses S. Org. Lett. 2020; 22: 2681
7c Yuan Z, Feng Z, Zeng Y, Zhao X, Lin A, Yao H. Angew. Chem. Int. Ed. 2019; 58: 2884
7d Zanghi JM, Liu S, Meek SJ. Org. Lett. 2019; 21: 5172
7e Zhu T, Lui Y, Smetankova M, Zhuo S, Mou C, Chai H, Jin Z, Chi YR. Angew. Chem. Int. Ed. 2019; 58: 15778
7f You C, Li X, Gong Q, Wen J, Zhang X. J. Am. Chem. Soc. 2019; 141: 14560
7g Knowe MT, Danneman MW, Sun S, Pink M, Johnston JN. J. Am. Chem. Soc. 2018; 140: 1998
7h Cai J, Wei Q, Hu X.-D, Zhang Y, Li W, Cong H, Liu W, Liu W.-B. Synthesis 2018; 50: 1661
7i Wu X, Chen Z, Bai Y.-B, Dong VM. J. Am. Chem. Soc. 2016; 138: 12013
7j Li Y, Yang S, Wen G, Lin Q, Zhang G, Qiu L, Zhang X, Du G, Fang X. J. Org. Chem. 2016; 81: 2763
7k Ema T, Akihara K, Obayashi R, Sakai T. Adv. Synth. Catal. 2012; 354: 3283
7l Deschamp J, Riant O. Org. Lett. 2009; 11: 1217
7m Ema T, Oue Y, Akihara K, Miyazaki Y, Sakai T. Org. Lett. 2009; 11: 4866

8a Zhao Y.-S, Tang X.-Q, Tao J.-C, Tian P, Lin G.-Q. Org. Biomol. Chem. 2016; 14: 4400
8b Molander GA, Huérou YL, Brown GA. J. Org. Chem. 2001; 66: 4511
8c Balog A, Geib J, Curran DP. J. Org. Chem. 1995; 60: 345
8d Villagómez-Ibarra R, Alvarez-Cisneros C, Joseph-Nathan P. Tetrahedron 1995; 51: 9285
8e Kinoshita A, Mori M. Chem. Lett. 1994; 23: 1475
8f Mori M, Kaneta N, Shibasaki M. J. Organomet. Chem. 1994; 464: 35

9a Mori M, Isono N, Kaneta N, Shibasaki M. J. Org. Chem. 1993; 58: 2972
9b Mori M, Isono N, Kaneta N, Shibasaki M. Tetrahedron Lett. 1991; 32: 6139

10 Schmidt W, Schulze TM, Brasse G, Nagrodzka E, Maczka M, Zettel J, Jones PG, Grunenberg J, Hilker M, Trauer-Kizilelma U, Braun U, Schulz S. Angew. Chem. Int. Ed. 2015; 54: 7698

Enantioselective syntheses through desymmetrization via intermolecular reactions of carbanion species are reported, see:

11a Graff J, Debande T, Praz J, Guénée L, Alexakis A. Org. Lett. 2013; 15: 4270
11b Perron Q, Alexakis A. Adv. Synth. Catal. 2010; 352: 2611
11c Hodgson DM, Štefane B, Miles TJ, Witherington J. J. Org. Chem. 2006; 71: 8510
11d Hodgson DM, Paruch E. Tetrahedron 2004; 60: 5185
11e Shintani R, Fu GC. Angew. Chem. Int. Ed. 2002; 41: 1057
11f Hodgson DM, Cameron ID. Org. Lett. 2001; 3: 441
11g Hodgson DM, Lee GP. Tetrahedron: Asymmetry 1997; 8: 2303

12 Martínez-Estíbalez U, Sotomayor N, Lete E. Org. Lett. 2009; 11: 1237 ; and references cited therein
13 Bedekar AV, Watanabe T, Tanaka K, Fuji K. Synthesis 1995; 1069
14 Byrne SJ, Fletcher AJ, Hebeisen P, Willis MC. Org. Biomol. Chem. 2010; 8: 758
15 Tomioka K, Shindo M, Koga K. J. Am. Chem. Soc. 1989; 111: 8266

16a Carl E, Stalke D. In Lithium Compounds in Organic Synthesis . Luisi R, Capriati V. Wiley-VCH; Weinheim: 2014: 3
16b Clayden J. Organolithiums: Selectivity for Synthesis . Elsevier Science; Oxford: 2002
16c Reich HJ. Chem. Rev. 2013; 113: 7130

17 Wei Z.-L, Li A.-Y, Lin G.-Q. Synthesis 2000; 1673
18 Yearick K, Wolf C. Org. Lett. 2008; 10: 3915

19a Alkenyl halides 7a,b were synthesized from ethyl propiolate by the following 3 steps: cis-addition of a hydrogen halide on the triple bond, reduction of the ester, and bromination of the alcohol. For cis-addition of a hydrogen halide on a triple bond, see: Ma S, Lu X, Li Z. J. Org. Chem. 1992; 57: 709
19b For conversion of an ester into allylic bromide, see: Shen Z, Ni Z, Mo S, Wang J, Zhu Y. Chem. Eur. J. 2012; 18: 4859

Supplementary Material

Supporting Information