New pyrrolidine-triazole-based C2 symmetric organocatalysts and their utility in the asymmetric Michael reaction of β-nitrostyrenes and the synthesis of nitrochromenes
Graphical abstract
Introduction
Asymmetric synthesis using organocatalysts is at the forefront of organic synthesis; the past decade has witnessed many contributions in this area.1 The development of new organocatalysts and new synthetic methodologies are two major components of research in this area.2 Since the discovery of l-proline-catalyzed asymmetric transformations,3 a number of proline-based organocatalysts have been developed.4 Among these, pyrrolidine-tetrazole,5 pyrrolidine-triazole,6 pyrrolidine-thiourea,7 and pyrrolidine-imidazolium8 conjugates, to name a few, have been successfully employed as catalysts for various asymmetric transformations. Asymmetric Michael addition and aldol condensation have been widely used to test the efficacy of new organocatalysts because of the importance of these two C–C bond-forming reactions in organic synthesis.9 Recent literature reveals the use of excellent pyrrolidine-triazole conjugate-based organocatalysts with a pyrrolidine unit as the catalytically active moiety and a triazole unit as the face-shielding group for the above transformations.6 Pyrrolidine-triazole-based organocatalysts supported on ionic liquids, polymers or silica gels have also been reported.10 Herein, the synthesis of three pyrrolidine-triazole conjugate catalysts is reported. It is envisaged that the apparent C2 symmetry in the bis(pyrrolidine-triazole) catalysts 3a–b might be beneficial for asymmetric transformations. We anticipated that the pyridine ring in 3a and 3c might provide additional hydrogen bonding sites and improve the catalytic activity. The catalytic activity and efficiency were tested using the well-known Michael addition of cyclohexanone to β-nitrostyrene. In addition, the asymmetric synthesis of nitrochromenes is reported using these catalysts.
Section snippets
Results and discussion
Organocatalysts 3a–c were synthesized by the Huisgen 1,3-dipolar cycloaddition of N-Boc-protected proline azide 2 (derived from l-proline)11 to the corresponding alkynes 1a–c followed by deprotection of the N-Boc group using TFA (Scheme 1).
Michael addition of cyclohexanone to β-nitrostyrene was used to screen the catalysts (Scheme 2, Table 1). The reactions were performed either in water or without any solvent under neat conditions. In all the cases, the syn isomer was obtained as the
Conclusion
In conclusion, we have described the synthesis of new bis(pyrrolidine-triazole)-based organocatalysts 3a–c and their utility in the asymmetric Michael reaction of β-nitrostyrenes. Organocatalyst 3a can able to mediate the Michael reaction without any additives and only with 5 equiv of cyclohexanone. The asymmetric synthesis of nitrochromenes from salicylaldehyde and β-nitrostyrene is also reported, albeit in poor enantioselectivities.
General
All reactions were carried out in oven-dried glasswares. Commercial reagents were used without purification. The reactions were monitored by TLC using silica gel plates (Silica gel 60 F254, Merck) and visualized either with UV light or with phosphomolybdic acid stain followed by heating. Column chromatography was carried out with Acme Silica Gel (100–200 mesh). NMR spectra were recorded in CDCl3 using TMS as internal standard at 400 MHz for 1H and 100 MHz for 13C using Bruker AV400 spectrometer.
References (15)
- et al.
Chem. Commun.
(2006)et al.Tetrahedron Lett.
(2007)et al.Catal. Today
(2007)et al.Org. Lett.
(2006) - et al.
Chem. Commun.
(2007)et al.J. Am. Chem. Soc.
(2000)et al.Org. Lett.
(2001)et al.Chem. Eur. J.
(2006)et al.Chem. Eur. J.
(2006)et al.Tetrahedron: Asymmetry
(2007)et al.J. Am. Chem. Soc.
(2006)et al.Org. Lett.
(2007)et al.Chem. Commun.
(2006)Eur. J. Org. Chem.
(2007)et al.Tetrahedron: Asymmetry
(2007) - et al.
Org. Lett.
(2003) - et al.
Angew. Chem., Int. Ed.
(2008)Chem. Commun.
(2006)et al.Org. Biomol. Chem.
(2005)et al.Aldrichim. Acta
(2006) - et al.
Angew. Chem., Int. Ed.
(2004)et al.Angew. Chem., Int. Ed.
(2007)et al.Tetrahedron
(2002)et al.Angew. Chem., Int. Ed.
(2006)et al.Tetrahedron: Asymmetry
(2006)Chem. Eur. J.
(2006) - (a)Hajos, Z. G.; Parrish, D. R. German Patent DE 2102623,...(b)Eder, U.; Sauer, G.; Wiechert, R. German Patent DE 2014757,... et al.
Angew. Chem., Int. Ed. Engl.
(1971)et al.J. Org. Chem.
(1974) Tetrahedron
(2002)Angew. Chem., Int. Ed.
(2008)Angew. Chem., Int. Ed.
(2003)
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