Organocatalytic Desymmetrisation of Fittig’s Lactones: Deuterium as a Reporter Tag for Hidden Racemisation

Péter Spránitz; Petra Sőregi; Bence Béla Botlik; Máté Berta; Tibor Soós

doi:10.1055/s-0037-1611655

Synthesis, Table of Contents

CC BY ND NC 4.0 · Synthesis 2019; 51(05): 1263-1272
DOI: 10.1055/s-0037-1611655

paper

Copyright with the author

Organocatalytic Desymmetrisation of Fittig’s Lactones: Deuterium as a Reporter Tag for Hidden Racemisation

Authors

Péter Spránitz
Petra Sőregi
Bence Béla Botlik
Máté Berta
Tibor Soós *

Institute of Organic Chemistry, Research Centre for Natural Sciences, Magyar tudósok körútja 2A, 1117 Budapest, Hungary Email: soos.tibor@ttk.mta.hu

Abstract

All articles of this category

Published as part of the 50 Years SYNTHESIS – Golden Anniversary Issue

Abstract

Highly enantioselective desymmetrisation of Fittig’s lactones with alcohols is promoted by bifunctional cinchona squaramides. The reactions were carried out with monodeuterated methanol to detect possible hidden racemisation of the stereogenic centre. Current evidence suggests that racemisation was not a relevant process for most substrates; partial erosion of enantioselectivity was only detected with ortho-substituted aryl derivates. The resultant glutaric acid derivatives possess a scaffold that is common in natural products and the compounds are also useful chiral building blocks for further synthetic endeavours.

Key words

Fittig’s lactone - desymmetrization - bislactone acylal - bifunctional organocatalysis - racemization

Full Text

References

References

1a Borissov A, Davies TQ, Ellis SR, Fleming TA, Richardson MS. W, Dixon DJ. Chem. Soc. Rev. 2016; 45: 5474
1b Suzuki T. Tetrahedron Lett. 2017; 58: 4731

2a For a recent review, see: Merad J, Candy M, Pons J.-M, Bressy C. Synthesis 2017; 49: 1938

Selected examples:

2b Phillips EM, Roberts JM, Scheidt KA. Org. Lett. 2010; 12: 2830
2c Higuchi K, Suzuki S, Ueda R, Oshima N, Kobayashi E, Tayu M, Kawasaki T. Org. Lett. 2015; 17: 154
2d Park KH, Chen DY.-K. Chem. Commun. 2018; 13018
2e Park J, Chen DY.-K. Angew. Chem. Int. Ed. 2018; 57: 16152

3a Chen Y, McDaid P, Deng L. Chem. Rev. 2003; 103: 2965
3b de Villegas MD, Gálvez JA, Etayo P, Badorrey R, López-Ram-de-Víu P. Chem. Soc. Rev. 2011; 40: 5564

4 Gualtierotti J.-B, Pasche D, Wang Q, Zhu J. Angew. Chem. Int. Ed. 2014; 53: 9926

5a Shim SH, Gloer JB, Wicklow DT. J. Nat. Prod. 2006; 69: 1601
5b Chen X.-L, Liu H.-L, Li J, Xin G.-R, Guo Y.-W. Org. Lett. 2011; 13: 5032
5c Weinaes K, Bahr W. Justus Liebigs Ann. Chem. 1969; 724: 214

6a Biber A, Koch E. Planta Med. 1999; 65: 192
6b Rossi R, Basilico F, Rossoni G, Riva A, Morazzoni P, Mauri PL. J. Pharm. Biomed. Anal. 2009; 50: 224
6c Woelkart K, Feizlmayr E, Dittrich P, Beubler E, Pinl F, Suter A, Bauer R. Phytother. Res. 2010; 24: 445

7a Acylals are cleaved by esterases and used in drug design: Gisch N, Balzarini J, Meier C. J. Med. Chem. 2007; 50: 1658
7b For a review on aldehyde acylals, see: Sydnes LK, Sandberg M. Proc. Indian Natn. Sci. Acad. Part A 2002; 68: 141

8 Fittig R. Justus Liebigs Ann. Chem. 1901; 314: 1

9a Ohsawa S, Morino K, Sudo A, Endo T. Macromolecules 2011; 44: 1814
9b Yamasaki R, Sudo A, Endo T. J. Polym. Sci., Part A: Polym. Chem. 2015; 53: 2462

10a Parker WL, Johnson F. J. Org. Chem. 1973; 38: 2489
10b Walraven HG. M, Pandit UK. Tetrahedron 1980; 36: 321
10c Strunz GM, Lal GS. Can. J. Chem. 1982; 60: 2528

11a Weise CF, Lauridsen VH, Rambo RS, Iversen EH, Olsen ML, Jørgensen KA. J. Org. Chem. 2014; 79: 3537
11b Jiang H, Albrecht Ł, Jørgensen KA. Chem. Sci. 2013; 4: 2287
11c Albrecht Ł, Dickmeiss G, Acosta FC, Rodríguez-Escrich C, Davis RL, Jørgensen KA. J. Am. Chem. Soc. 2012; 134: 2543

12a Malerich JP, Hagihara K, Rawal VH. J. Am. Chem. Soc. 2008; 130: 14416
12b For a review on squaramides, see: Alemán J, Parra A, Jiang H, Jørgensen KA. Chem. Eur. J. 2011; 17: 6890
12c Mechanism: Kótai B, Kardos G, Hamza A, Farkas V, Pápai I, Soós T. Chem. Eur. J. 2014; 20: 5631

13a Li B.-J, Jiang L, Liu M, Chen Y.-Ch, Ding L.-S, Wu Y. Synlett 2005; 603
13b Vakulya B, Varga S, Csámpai A, Soós T. Org. Lett. 2005; 7: 1967
13c McCooey SH, Connon SJ. Angew. Chem. Int. Ed. 2005; 44: 6367
13d Ye J, Dixon DJ, Peter S, Hynes PS. Chem. Commun. 2005; 4481
13e Mechanism: Hamza A, Schubert G, Soós T, Pápai I. J. Am. Chem. Soc. 2006; 128: 13151

14 Berkes B, Ozsváth K, Molnár L, Gáti T, Holczbauer T, Kardos G, Soós T. Chem. Eur. J. 2016; 22: 18101
15 For details see the Supporting Information.

16a Dedeoglu B, Catak S, Houk KN, Aviyente V. ChemCatChem 2010; 2: 1122
16b Blise K, Cvitkovic MW, Gibbs NJ, Roberts SF, Whitaker RM, Hofmeister GE, Kohen D. J. Org. Chem. 2017; 82: 1347

17 Mechanism of lactone hydrolysis: Gómez-Bombarelli R, Calle E, Casado J. J. Org. Chem. 2013; 78: 6868
18 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich AV, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery JA. Jr, Peralta JE, Ogliaro F, Bearpark MJ, Heyd JJ, Brothers EN, Kudin KN, Staroverov VN, Keith TA, Kobayashi R, Normand J, Raghavachari K, Rendell AP, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ. Gaussian 16, Revision B.01. Gaussian, Inc; Wallingford CT: 2016