An efficient synthesis of styrenyl enamides from 4-aryl-2-oxazolidinones in the presence of strong baseby Kaihe Zou, Jinxing Ye, Xin-Yan Wu

Tetrahedron Letters

About

Year
2015
DOI
10.1016/j.tetlet.2015.08.026
Subject
Organic Chemistry / Biochemistry / Drug Discovery

Similar

Text

id e o on, S ity o vers yl e 2-th eede  2015 Elsevier Ltd. All rights reserved. tant sc diates s can es, imi nyl enamides, the development of their preparation remains challenging and synthetically useful.

Because of widespread applications of styrenyl enamides, many efforts have been made toward to general, efficient, and stereoselective methods access to this class of compounds. Different methods could be applied to synthesize these enamides (Scheme 1), including traditional approaches such as direct condensations of de a broad scope enyl-3-pro ts and ba failed to obtain the a-arylation product (Scheme 2). It is very esting that the starting material was transformed into en after careful purification and characterization with NMR, was further confirmed by single-crystal X-ray crystallography.

Owing to the interesting transformation and the significance of styrenyl enamides, we decided to investigate the reaction in details.

We initially studied the reaction of 4-phenyl-3-propionyloxazolidin-2-one (1a) with various additives in THF at 78 C. As shown in Table 1, no reaction occurred with potassium tert-butoxide, ⇑ Corresponding authors. Tel.: +86 21 64252011; fax: +86 21 64252758.

E-mail addresses: yejx@ecust.edu.cn (J. Ye), xinyanwu@ecust.edu.cn (X.-Y. Wu).

Tetrahedron Letters 56 (2015) 5517–5520

Contents lists availab ro .e lamides building blocks with chiral catalyst including metal complexes and organic molecules.2 In recent years, more and more such compounds are used for stereoselective C–C and C–N bond forming reactions.3 In spite of the extensive applications of styresynthesis of enamides. This process could provi of styrenyl enamides in high yields.

When we tried to run the a-arylation of 4-ph oxazolidin-2-one (1a) with diaryliodonium salhttp://dx.doi.org/10.1016/j.tetlet.2015.08.026 0040-4039/ 2015 Elsevier Ltd. All rights reserved.pionylse, we interamide whichtors in the presence of a suitable Lewis acid catalyst. With metal catalyst, the a- and b-carbon of styrenyl enamides can be regioselective functionalized.1f The products so generated can be easily transformed to other nitrogen-containing compounds or other functional groups. On the other hand, styrenyl enamides are remarkable substrates in a range of asymmetric reactions.1c

Especially, they were frequently utilized in asymmetric hydrogenation for the synthesis of various chiral amines and amides, and the Heck reaction of N-vinyl amide with aryl triflates or halide compounds.7 In the recent decades, great progress has been achieved in the preparation of enamides. According to the references, reducing agents have been developed in this catalyzed reductive acylation reaction.8–15

Aiming at the development of a more direct and friendly process, herein we report a direct, very rapid, relatively mild, and efficient procedure that promoted by the strong base LDA for theKeywords:

Enamides

Lithium diisopropylamine

Oxazolidinones

Thioxooxazolidines

Thioxothiazolidines

Enamides are present as an impor natural products, and key interme

Among them, the styrenyl enamide perform addition to aldehydes/ketonaffold in various drugs, in organic synthesis.1 act as a nucleophile to nes, and Michael accep1a,b amides to ketones with catalysts,4 the addition of organomagnesium or organolithium reagents to nitriles as intermediates and then constructing enamides with different substances,5 the metal-catalyzed cross coupling of alkenyl compounds with 6Available online 14 August 2015 92%). This reaction provides an easy, rapid, and good-yielding method for the synthesis of styrenyl enamides.An efficient synthesis of styrenyl enam 4-aryl-2-oxazolidinones in the presenc

Kaihe Zou a,c, Jinxing Ye a,b,⇑, Xin-Yan Wu c,⇑ a Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Educati

Road, Shanghai 200237, China b Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China Univers cKey Laboratory for Advanced Materials and Institute of Fine Chemicals, East China Uni a r t i c l e i n f o

Article history:

Received 11 June 2015

Revised 4 August 2015

Accepted 10 August 2015 a b s t r a c t

Efficient synthesis of styren 2-thioxooxazolidines, and lamine. The reaction proc

Tetrahed journal homepage: wwwes from f strong base chool of Pharmacy, East China University of Science and Technology, 130 Meilong f Science and Technology, 130 Meilong Road, Shanghai 200237, China ity of Science and Technology, 130 Meilong Road, Shanghai 200237, China namides can be achieved from the corresponding 4-aryl-2-oxazolidinones, ioxothiazolidines in the presence of the strong base lithium diisopropyd efficiently to achieve the enamides in good to excellent yields (up to le at ScienceDirect n Letters sevier .com/ locate/ tet le t obtained in 70%, 85%, and 78% yield correspondingly (entries 6–8). As we known, Kinoshita and co-workers reported a procedure to prepare (E)-a,b-didehydroamino acid derivatives by reaction of cis-4,5-oxazolidinone and LiHMDS, which shared a similar chemistry with this work, and they obtained the desired products in good yield and high E selectivity.16 Next the effect of different solvents was subsequently surveyed (entries 9–11). The results indicated that the reaction performed well in both ether and alkane solvents, while all the solvents gave the desired product in moderate yield. Further increasing the reaction time did not provide a better result (entry 12). Thus, the best optimized conditions for this reaction have been established, LDA as the strong base in

THF at 78 C for 30 min.

With the optimal reaction conditions in hand, the substrate scope of the reaction was then investigated. A variety of differently substituted oxazolidinones 1 were subjected to the above reaction conditions. The results are shown in Table 2. It is satisfactory that all the reactions completed in short reaction time, and provided the desired products in good to excellent yields, exhibiting good functional group and extensive N-acyl group tolerance. The reactions of oxazolidone substrates with alkyl acetyl groups gave excellent yields (3a–f). Among these results, oxazolidinones with bulky acetyl groups gave slightly high yield (3e and 3f), probably due to