Diastereo- and Enantioselective [3 + 3] Cycloaddition of Spirocyclopropyl Oxindoles Using Both Aldonitrones and Ketonitrones

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Nov 22

PMID 29158496

Citations 6

Authors

Peng-Wei Xu

Jia-Kuan Liu

Lan Shen

Zhong-Yan Cao

Xiao-Li Zhao

Jun Yan

Jian Zhou

Affiliations

Soon will be listed here.

Abstract

Optically active spirocyclic compounds play an important role in drug discovery, and new synthetic strategies for the efficient generation of spiro stereocenters are in much demand. Here we report a catalytic enantioselective cycloaddition using spirocyclic donor-acceptor cyclopropanes as a promising approach for the generation of spiro stereocenters. A diastereo- and enantioselective [3 + 3] cycloaddition of spirocyclopropyl oxindoles with both aldonitrones and ketonitrones is developed. The key to reaction development is the activation of spirocyclopropyl oxindoles by a suitable electron-withdrawing N-protecting group. This activation approach offers the promise of a general solution to enable spirocyclopropyl oxindoles as synthons for catalytic enantioselective synthesis of spirocyclic oxindoles featuring a C3 spiro stereocenter, a prominent structural motif in drugs and pharmaceutically active compounds. This protocol also constitutes the catalytic enantioselective reaction using unactivated achiral ketonitrones to construct tetrasubstituted carbon stereocenters.

Citing Articles

2-Oxindole and related heterocycles: synthetic methodologies for their natural products and related derivatives.

Sharma S, Monga Y, Gupta A, Singh S RSC Adv. 2023; 13(21):14249-14267.

PMID: 37179999 PMC: 10173257. DOI: 10.1039/d3ra02217j.

Asymmetric synthesis of chiral 1,2-oxazinane and hexahydropyridazin spirocyclic scaffolds by organocatalytic [4 + 2] cycloaddition.

Tian H, Tang Q, Lin G, Sun X RSC Adv. 2022; 12(25):15713-15717.

PMID: 35685709 PMC: 9128346. DOI: 10.1039/d2ra02759c.

Enantioselective (8+3) Cycloadditions by Activation of Donor-Acceptor Cyclopropanes Employing Chiral Brønsted Base Catalysis.

McLeod D, Thogersen M, Barlose C, Skipper M, Obregon E, Anker Jorgensen K Angew Chem Int Ed Engl. 2022; 61(29):e202206096.

PMID: 35580010 PMC: 9401081. DOI: 10.1002/anie.202206096.

Highly stereoselective spirocyclopropanation of various diazooxindoles with olefins catalyzed using Ru(ii)-complex.

Tone M, Nakagawa Y, Chanthamath S, Fujisawa I, Nakayama N, Goto H RSC Adv. 2022; 8(70):39865-39869.

PMID: 35558243 PMC: 9092356. DOI: 10.1039/c8ra09212e.

Catalytic (3 + 2) annulation of donor-acceptor aminocyclopropane monoesters and indoles.

Pirenne V, Robert E, Waser J Chem Sci. 2021; 12(25):8706-8712.

PMID: 34257869 PMC: 8246098. DOI: 10.1039/d1sc01127h.

References

Sharma I, Tan D . Drug discovery: Diversifying complexity. Nat Chem. 2013; 5(3):157-8. DOI: 10.1038/nchem.1581. View

Jia Z, Jiang H, Li J, Gschwend B, Li Q, Yin X . Trienamines in asymmetric organocatalysis: Diels-Alder and tandem reactions. J Am Chem Soc. 2011; 133(13):5053-61. DOI: 10.1021/ja1112194. View

Carson C, Kerr M . Heterocycles from cyclopropanes: applications in natural product synthesis. Chem Soc Rev. 2009; 38(11):3051-60. DOI: 10.1039/b901245c. View

Pulz R, Al-Harrasi A, Reissig H . New polyhydroxylated pyrrolidines derived from enantiopure 3,6-dihydro-2H-1,2-oxazines. Org Lett. 2002; 4(14):2353-5. DOI: 10.1021/ol0260573. View

Bencivenni G, Wu L, Mazzanti A, Giannichi B, Pesciaioli F, Song M . Targeting structural and stereochemical complexity by organocascade catalysis: construction of spirocyclic oxindoles having multiple stereocenters. Angew Chem Int Ed Engl. 2009; 48(39):7200-3. DOI: 10.1002/anie.200903192. View

Kang Y, Sun X, Tang Y . Highly enantioselective and diastereoselective cycloaddition of cyclopropanes with nitrones and its application in the kinetic resolution of 2-substituted cyclopropane-1,1-dicarboxylates. Angew Chem Int Ed Engl. 2007; 46(21):3918-21. DOI: 10.1002/anie.200604645. View

Soholm Halskov K, Kniep F, Lauridsen V, Iversen E, Donslund B, Anker Jorgensen K . Organocatalytic enamine-activation of cyclopropanes for highly stereoselective formation of cyclobutanes. J Am Chem Soc. 2015; 137(4):1685-91. DOI: 10.1021/ja512573q. View

Quasdorf K, Overman L . Catalytic enantioselective synthesis of quaternary carbon stereocentres. Nature. 2014; 516(7530):181-91. PMC: 4697831. DOI: 10.1038/nature14007. View

Shi F, Zhu R, Dai W, Wang C, Tu S . Catalytic asymmetric formal [3+3] cycloaddition of an azomethine ylide with 3-indolylmethanol: enantioselective construction of a six-membered piperidine framework. Chemistry. 2014; 20(9):2597-604. DOI: 10.1002/chem.201304187. View

10.

Meazza M, Rios R . Synergistic Catalysis: Enantioselective Ring Expansion of Vinyl Cyclopropanes Combining Four Catalytic Cycles for the Synthesis of Highly Substituted Spirocyclopentanes Bearing up to Four Stereocenters. Chemistry. 2016; 22(29):9923-8. DOI: 10.1002/chem.201601893. View

11.

Liu R, Ye S, Lu C, Zhuang G, Gao J, Jia Y . Dual catalysis for the redox annulation of nitroalkynes with indoles: enantioselective construction of indolin-3-ones bearing quaternary stereocenters. Angew Chem Int Ed Engl. 2015; 54(38):11205-8. DOI: 10.1002/anie.201504697. View

12.

Parsons A, Johnson J . Catalytic enantioselective synthesis of tetrahydrofurans: a dynamic kinetic asymmetric [3 + 2] cycloaddition of racemic cyclopropanes and aldehydes. J Am Chem Soc. 2009; 131(9):3122-3. DOI: 10.1021/ja809873u. View

13.

Grover H, Emmett M, Kerr M . Carbocycles from donor-acceptor cyclopropanes. Org Biomol Chem. 2014; 13(3):655-71. DOI: 10.1039/c4ob02117g. View

14.

Xia Y, Liu X, Zheng H, Lin L, Feng X . Asymmetric synthesis of 2,3-dihydropyrroles by ring-opening/cyclization of cyclopropyl ketones using primary amines. Angew Chem Int Ed Engl. 2014; 54(1):227-30. DOI: 10.1002/anie.201407880. View

15.

Xu H, Qu J, Liao S, Xiong H, Tang Y . Highly enantioselective [3+2] annulation of cyclic enol silyl ethers with donor-acceptor cyclopropanes: accessing 3a-hydroxy [n.3.0]carbobicycles. Angew Chem Int Ed Engl. 2013; 52(14):4004-7. DOI: 10.1002/anie.201300032. View

16.

Marti C, Carreira E . Total synthesis of (-)-spirotryprostatin B: synthesis and related studies. J Am Chem Soc. 2005; 127(32):11505-15. DOI: 10.1021/ja0518880. View

17.

Selim K, Martel A, Laurent M, Lhoste J, Py S, Dujardin G . Enantioselective ruthenium-catalyzed 1,3-dipolar cycloadditions between C-carboalkoxy ketonitrones and methacrolein: solvent effect on reaction selectivity and its rational. J Org Chem. 2014; 79(8):3414-26. DOI: 10.1021/jo5001737. View

18.

Jackson S, Karadeolian A, Driega A, Kerr M . Stereodivergent methodology for the synthesis of complex pyrrolidines. J Am Chem Soc. 2008; 130(12):4196-201. DOI: 10.1021/ja710289k. View

19.

Lerchner A, Carreira E . First total synthesis of (+/-)-strychnofoline via a highly selective ring-expansion reaction. J Am Chem Soc. 2002; 124(50):14826-7. DOI: 10.1021/ja027906k. View

20.

Trost B, Morris P, Sprague S . Palladium-catalyzed diastereo- and enantioselective formal [3 + 2]-cycloadditions of substituted vinylcyclopropanes. J Am Chem Soc. 2012; 134(42):17823-31. PMC: 3495600. DOI: 10.1021/ja309003x. View