Chinese Chemical Letters 29 (2018) 942–944
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Enantioselective organocatalytic synthesis of the chiral chromenes by domino oxa-Michael-aldol reaction Shrikant S. Pendalwar, Avinash V. Chakrawar, Sudhakar R. Bhusare* Department of Chemistry, Dnyanopasak College, Parbhani 431 401, MS, India
A R T I C L E I N F O
Article history: Received 24 June 2017 Received in revised form 14 September 2017 Accepted 28 September 2017 Available online 3 October 2017 Keywords: Asymmetric synthesis L-Proline Organocatalyst 2-Aryl-2H-chromenes-3-carbaldehyde
A B S T R A C T
The proline based chiral organocatalyst has been found to be an efﬁcient catalyst for the facile synthesis of substituted 2-aryl-2H-chromenes-3-carbaldehyde. We envisioned that the iminium interaction between chiral amino catalysts and a,b-unsaturated carbonyl group was beneﬁcial along with thiourea group as hydrogen bond donor, heterocyclic amines as general base in the domino oxa-Michael-aldol reaction. This catalytic system provided the products in good to high yields (73%–96%) with excellent enantioselectivity (up to 97%) and reasonable reaction time. The atom economy, high yield and mild reaction conditions are some of the important features of this protocol. © 2017 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
The scope and stereoselectivities achieved by organocatalysts had grown remarkably over the past decade. Organocatalytic reactions are usually considered as operationally easy and ecofriendly because the use of metals is avoided. Organocatalytic enantioselective systems have rapidly grown and found to be a very exciting ﬁeld in organic chemistry and chiral secondary amines are perhaps the most frequently used organocatalysts, which activate substrates either by raising the highest occupied molecular orbital energy level or lowering the lowest unoccupied molecular orbital energy level . Heterocycles plays a vital role in the design and discovery of new physiologically active compounds . The benzopyrans also belong among these privileged structures, as depict and revealed by Nicolaou et al. [3,4]. The condensation reactions between Michael acceptors and salicylaldehydes have conﬁrmed to be a useful route to benzopyrans . Although asymmetric methods would furnish enantiomerically enriched chromenes, their development has proven to be a synthetic challenging task. By taking advantage of the capability of chiral proline derivatives to participate in the reversible formation of enamine and iminium intermediates, Enders Yamamoto, Jorgenson and List have independently developed novel types of organocatalyzed cascade reactions [1,6,7]. Michael addition initiated cascade Michael-aldol processes serve as powerful methods for the generation of complex structures.
* Corresponding author. E-mail address: [email protected]
Compared with the proline amide catalyst, proline with thiourea moiety having pyrrolidine ring, two hydrogen atoms on thiourea involved in hydrogen bonding and aromatic or cyclic amine as general base are functional centers in the backbone of the catalyst. It exerts stronger inﬂuence on the orientation of the iminium intermediate formed between a,b-unsaturated carbonyl and organocatalyst to enhance the stereoselectivities for the domino oxa-Michael-aldol reaction. Herein we reported the asymmetric synthesis of chiral chromenes via organocatalytic domino oxa-Michael-aldol reaction using proline based chiral organocatalyst. The strategy we presented here is the utilization of a proline based chiral organocatalyst as a promoter for activation of the Michael acceptor 5 in a highly enantioselective controlled manner (Table 1). As our earlier interest in synthesis and study of proline based chiral organocatalysts , we envisioned that the iminium interaction between chiral amino catalysts and a,b-unsaturated carbonyl group was beneﬁcial along with thiourea group as hydrogen bond donor, heterocyclic amines as general base in the domino oxaMichael-aldol reaction of simple a,b-unsaturated aromatic aldehydes and salicylaldehydes. All solvents were used as commercial anhydrous grade without further puriﬁcation. Aluminium sheets 20 cm 20 cm, Silica gel 60 F254, Merck grade was used for thin layer chromatography to determine the progress of reaction. The column chromatography was carried out over silica gel (80–120 mesh). Optical rotations were measured on a Polax-2L digital polarimeter. 1H NMR and 13C NMR spectra were recorded on a Bruker 300 MHz spectrometer. Melting points were measured in open capillary. Enantiomeric
https://doi.org/10.1016/j.cclet.2017.09.058 1001-8417/ © 2017 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
S.S. Pendalwar et al. / Chinese Chemical Letters 29 (2018) 942–944 Table 1 Screening of the catalyst and catalytic loading for the domino oxa-Michael-aldol reactiona .
Table 2 Screening of the solvent in domino oxa-Michael-aldol reactiona .
c ½a25 D
c ½a25 D
1 2 3 4 5 6
3a 3b 3c 3d 3a 3a
5 5 5 5 8 10
26 28 28 28 24 22