The Baylis-Hillman Reaction: One-Pot Stereoselective Synthesis of Methyl (2E)-3-Aryl-2-hydroxymethylprop-2-enoates

Abstract

A facile, simple and one-pot conversion of methyl 3-aryl-3-hydroxy-2-methylenepropanoates into methyl (2E)-3-aryl-2-hydroxymethylprop-2-enoates via the sequential treatment with acetic anhydride/trimethylsilyl trifluoromethanesulfonate (TMSOTf) and potassium carbonate/methanol is described.The Baylis-Hillman reaction has been and continues to be an interesting carbon-carbon bond forming reaction providing a useful class of densely functionalized molecules whose applications in a variety of stereoselective transformations have been well documented in the literature. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] In continuation of our interest in the development of the Baylis-Hillman reaction as a potential source for stereoselective processes, 9-14 we herein report simple, convenient and one-pot stereoselective transformation of methyl 3-aryl-3-hydroxy-2-methylenepropanoates, the Baylis-Hillman adducts obtained from the activated alkene, methyl acrylate, into methyl (2E)-3-aryl-2-hydroxymethylprop-2-enoates via the successive treatment with acetic anhydride/trimethylsilyl trifluoromethanesulfonate (TMSOTf), and potassium carbonate/methanol in very good yields.(2E)-2-Hydroxymethylalk-2-enoic acids and their esters are useful synthons for synthesis of various biologically active molecules. [15][16][17][18][19][20][21][22] However, there are only a few methods available in the literature for synthesis of these important molecules. [18][19][20][21][22] It is interesting to note that (m)ethyl 3-hydroxy-2-methylenealkanoates, the Baylis-Hillman adducts obtained from (m)ethyl acrylate, have been a major source for obtaining these (2E)-2-hydroxymethylalk-2-enoic acid derivatives. Thus, (m)ethyl 3-hydroxy-2-methylenealkanoates have been transformed into the desired (m)ethyl (2E)-2-hydroxymethylalk-2-enoates in three different elegant ways. The first involves a three step sequence, bromination-formylation-hydrolysis, 20 the second deals with bromination-acetylation-hydrolysis, 18 while the third method uses DEAD/PPh 3 (Mitsunobu conditions) reagent to first obtain the O-protected alcohol, which on hydrolysis provides the desired (E)-allylic alcohols. 19,22 All these methods, though simple, involve at least two steps. In view of the importance of these molecules we felt that it would be desirable and more useful if methyl 3-hydroxy-2-methylenealkanoates can be converted in an operationally simple one-pot procedure directly into methyl (2E)-2-hydroxymethylalk-2-enoates.We have recently reported a convenient aqueous sulfuric acid mediated isomerization of 3-hydroxy-3-aryl-2-methylenepropanenitriles into (E)-a-cyanocinnamyl alcohols. 13 Our attempts to extend a similar aqueous sulfuric acid mediated isomerization reaction to methyl 3-hydroxy-2-methylenealkanoates were not successful. Based on our recent report on the trimethylsilyl trifluoromethanesulfonate (TMSOTf) catalyzed isomerization of methyl 3-aryl-3-acetoxy-2-methylenepropanoates into methyl (2E)-3-aryl-2-acetoxymethylprop-2-enoates, 14 we envisioned that we can firs...

Montmorillonite K10 Clay-Microwave Assisted Isomerisation of Acetates of the Baylis-Hillman Adducts: A Facile Method of Stereoselective Synthesis of (E)-Trisubstituted Alkenes

“…In the 13 C NMR spectra of trisubstituted olefins, the allylic carbon cis to aromatic group appears up field while the same carbon trans to aromatic ring appears down field. The values we obtained herein are exactly matching with the values reported 8,9 in the literature.…”

“…The Baylis-Hillman reaction is one of the important Carbon-Carbon bond forming reactions and has been used in organic synthesis for the synthesis of a variety of compounds having diverse functional groups and has been used as the starting point for a variety of synthetic organic transformations. [5][6][7][8][9][10][11][12][13] Stereoselective synthesis of (E)-trisubstituted alkenes is one of the difficult tasks in organic synthesis and only a few methods are known in the literature. 8,9,14 Stereoselective isomerisation of acetates of Baylis-Hillman adducts catalyzed by TM-SOTf, 8,9 trifluoroacetic acid, 10 benzyl-trimethylammonium fluoride 11 have appeared in the literature.…”

Recent Advances in the Baylis−Hillman Reaction and Applications

“…About the same time, we also developed an alternative, simple, and one-pot stereoselective synthesis of methyl (2 E )-3-aryl-2-(hydroxymethyl)prop-2-enoates via the sequential treatment of methyl 3-aryl-3-hydroxy-2-methylenepropanoates with Ac 2 O/TMSOTf and K 2 CO 3 in methanol (Scheme ) 124 …”

“…371 About the same time, we also developed an alternative, simple, and one-pot stereoselective synthesis of methyl (2E)-3-aryl-2-(hydroxymethyl)prop-2-enoates via the sequential treatment of methyl 3-aryl-3hydroxy-2-methylenepropanoates with Ac 2 O/TMSOTf and K 2 CO 3 in methanol (Scheme 124). 372 Subsequently, stereoselective isomerization of acetates of the Baylis-Hillman adducts have also been achieved by Shanmugam and Singh using the montmorillonite K10 clay microwave to furnish the (E)trisubstituted alkenes in high yields (eq 76). 373…”

Metal–Organic Self-Assembled Trefoil Knots for C—Br Bond Activation

“…In fact, it has been shown that even species with moderate binding affinities toward halides can enhance reactions involving carbon–halogen bond cleavage. − On account of their relatively high binding constants, we speculated that our knots can efficiently catalyze reactions that involve the cleavage of carbon–halogen bonds by stabilizing the bromide leaving group through CH···Br – interactions and long-range M···Br – electrostatic interactions (Scheme ). Therefore, we employed our metal–organic knots as catalysts in the hydrolysis of stereodefined bromo olefin-based derivatives of Baylis–Hillman adducts, − the products of which are widely used in the preparation of various natural and bioactive compounds. − …”