Stereoselective Total Synthesis of (+)-Casuarine via a Functionalized Pyrrolidine

Abstract

The stereoselective total synthesis of (+)-casuarine has been achieved via a functionalized pyrrolidine obtained from a chiral 1,3-oxazine. The synthetic strategy includes a stereoselective dihydroxylation reaction using osmium tetroxide and stereoselective Grignard-type vinyl addition reaction as the key steps to generate the two new stereocenters. The dihydroxylation catalyzed by osmium tetroxide formed anti-amino alcohol, and the vinyl addition formed syn-alcohol. (+)-Casuarine was prepared from the functionalized pyrrolidine over 11 steps in an overall yield of 16%.

Key words

total synthesis - natural products - stereoselective synthesis - dihydroxylation - Grignard reaction - annulation - heterocycles

Publication History

Received: 25 November 2021

Accepted after revision: 20 December 2021

Article published online:
14 February 2022

• References

• 1a Kim J.-S, Kang J.-C, Yoo G.-H, Jin X, Myeong I.-S, Oh C.-Y, Ham W.-H. Tetrahedron 2015; 71: 2772
• 1b Park S.-H, Jin X, Kang J.-C, Jung C, Kim S.-S, Kim S.-S, Lee K.-Y, Ham W.-H. Org. Biomol. Chem. 2015; 13: 4539
• 1c Kim J.-S, Kim G.-W, Kang J.-C, Myeong I.-S, Jung C, Lee Y.-T, Choo G.-H, Park S.-H, Lee G.-J, Ham W.-H. Tetrahedron: Asymmetry 2016; 27: 171
• 1d Kim J.-S, Lee Y.-T, Lee K.-H, Myeong I.-S, Kang J.-C, Jung C, Park S.-H, Ham W.-H. J. Org. Chem. 2016; 81: 7432
• 1e Myeong I.-S, Kim J.-S, Lee Y.-T, Kang J.-C, Park S.-H, Jung C, Ham W.-H. Tetrahedron: Asymmetry 2016; 27: 823
• 1f Myeong I.-S, Jung C, Kim J.-Y, Park S.-H, Ham W.-H. Tetrahedron Lett. 2018; 59: 2422
• 1g Myeong I.-S, Ham W.-H. Tetrahedron 2019; 75: 3832
• 1h Myeong I.-S, Jung C, Ham W.-H. Synthesis 2019; 51: 3471
• 1i Myeong I.-S, Lee Y.-T, Kang J, Ham W.-H. J. Org. Chem. 2019; 84: 4211
• 1j Myeong IS, Ham WH. Eur. J. Org. Chem. 2019; 1077
• 2 Kim J.-Y, Mu Y, Jin X, Park S.-H, Pham V.-T, Song D.-K, Lee K.-Y, Ham W.-H. Tetrahedron 2011; 67: 9426
• 3 Nash RJ, Thomas PI, Waigh RD, Fleet GW. J, Wormald MR, Lilley PM. d. Q, Watkin DJ. Tetrahedron Lett. 1994; 35: 7849
• 4a Matsumura T, Kasai M, Hayashi T, Arisawa M, Momose Y, Arai I, Amagaya S, Komatsu Y. Pharm. Biol. 2000; 38: 302
• 4b Cardona F, Faggi E, Liguori F, Cacciarini M, Goti A. Tetrahedron Lett. 2003; 44: 2315
• 4c Kato A, Kano E, Adachi I, Molyneux RJ, Watson AA, Nash RJ, Fleet GW, Wormald MR, Kizu H, Ikeda K. Tetrahedron: Asymmetry 2003; 14: 325
• 4d Cardona F, Parmeggiani C, Faggi E, Bonaccini C, Gratteri P, Sim L, Gloster TM, Roberts S, Davies GJ, Rose DR. Chem. Eur. J. 2009; 15: 1627
• 4e Bonaccini C, Chioccioli M, Parmeggiani C, Cardona F, Lo Re D, Soldaini G, Vogel P, Bello C, Goti A, Gratteri P. Eur. J. Org. Chem. 2010; 5574
• 4f Ritthiwigrom T, Pyne SG. Stud. Nat. Prod. Chem. 2012; 36: 1-26
• 5a Denmark SE, Hurd AR. Org. Lett. 1999; 1: 1311
• 5b Denmark SE, Hurd AR. J. Org. Chem. 2000; 65: 2875
• 6 Izquierdo I, Plaza MT, Tamayo JA. Tetrahedron 2005; 61: 6527
• 7 Van Ameijde J, Horne G, Wormald MR, Dwek RA, Nash RJ, Jones PW, Evinson EL, Fleet GW. Tetrahedron: Asymmetry 2006; 17: 2702
• 8a Cardona F, Parmeggiani C, Faggi E, Bonaccini C, Gratteri P, Sim L, Gloster TM, Roberts S, Davies GJ, Rose DR, Goti A. Chem. Eur. J. 2009; 15: 1627
• 8b Parmeggiani C, Cardona F, Giusti L, Reissig HU, Goti A. Chem. Eur. J. 2013; 19: 10595
• 9 Ritthiwigrom T, Willis AC, Pyne SG. J. Org. Chem. 2010; 75: 815
• 10 Concia AL, Gómez L, Parella T, Joglar J, Clapés P. J. Org. Chem. 2014; 79: 5386
• 11 Li Y.-X, Wang J.-Z, Kato A, Shimadate Y, Kise M, Jia Y.-M, Fleet GW, Yu C.-Y. Org. Biomol. Chem. 2021; 19: 9410
• 12a VanRheenen V, Kelly RC, Cha DY. Tetrahedron Lett. 1976; 1973
• 12b Tian Y.-S, Joo J.-E, Kong B.-S, Pham V.-T, Lee K.-Y, Ham W.-H. J. Org. Chem. 2009; 74: 3962
• 13a Kiyooka S, Nakano M, Shiota F, Fujiyama R. J. Org. Chem. 1989; 54: 5409
• 13b Myeong I.-S, Lee Y.-T, Lee S.-H, Jung C, Kim J.-S, Park S.-H, Kang J, Lee S.-J, Ye I.-H, Ham W.-H. Tetrahedron: Asymmetry 2017; 28: 1053
• 13c Myeong I.-S, Lee S.-H, Ham W.-H. Tetrahedron 2018; 74: 3888
• 14 The geometries were optimized with molecular modeling (MMFF) followed by density functional calculations (DFT) at the B3LYP level with 6-311+g(d,p) as basis set (Gaussian09, by Gaussian, Inc.) in the gas phase.
• 15 Please see the Supporting Information for further details.

For selective reports of stereoselective Upjohn dihydroxylations, see:
• 16a Corey E, Danheiser RL, Chandrasekaran S, Siret P, Keck GE, Gras JL. J. Am. Chem. Soc. 1978; 100: 8031
• 16b Cha JK, Christ W, Kishi Y. Tetrahedron Lett. 1983; 24: 3943
• 16c Cha JK, Kim N.-S. Chem. Rev. 1995; 95: 1761
• 17a Boschelli D, Takemasa T, Nishitani Y, Masamune S. Tetrahedron Lett. 1985; 26: 5239
• 17b Nicolaou K, Webber S. Synthesis 1986; 453
• 18a Keck GE, Andrus MB, Romer DR. J. Org. Chem. 1991; 56: 417
• 18b Venkatesan K, Srinivasan K. Tetrahedron: Asymmetry 2008; 19: 209
• 18c Sabitha G, Reddy CN, Gopal P, Yadav J. Tetrahedron Lett. 2010; 51: 5736
• 18d Yadav JS, Chinnam VV, Krishna BB. M, Rao KL. S, Das S. Tetrahedron Lett. 2015; 56: 1661
• 19 Davies SG, Fletcher AM, Roberts PM, Thomson JE. Synlett 2017; 28: 2697
• 20 Peaks in ¹H NMR and ¹³C NMR spectra of the compound are broad and split due to the presence of N-Cbz rotamers.