Trifluoroacetic anhydride—catalyzed conjugate addition of boronic acids to a,b-unsaturated ketones Silvia Roscales, Ángela Rincón, Eduardo Buxaderas, Aurelio G. Csákÿ ⇑ Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense, Paseo Juan XXIII, 1. E-28040 Madrid, Spain article info Article history: Received 11 May 2012 Revised 18 June 2012 Accepted 22 June 2012 Available online 2 July 2012 Keywords: Conjugate addition Boronic acids a,b-Unsaturated ketone Acid anhydride Catalysis abstract The conjugate addition of boronic acids to a,b-unsaturated ketones catalyzed by acylating reagents has been explored. The results show that trifluoroacetic anhydride catalyzes the addition of vinylboronic acids under experimentally simple and metal-free conditions for a variety of substrates with good yields. Ó 2012 Elsevier Ltd. All rights reserved. The formation of C–C bonds is pivotal in the building of complex organic molecules. The development of new synthetic procedures which enable the selective formation of this type of linkage under mild reaction conditions is an area of active research. Among these methods, the conjugate addition reaction of carbon nucleophiles to electron-deficient alkenes has become one of the most important. 1 In particular, the conjugate addition reaction of boronic acids to a wide variety of electron-deficient systems under transition-metal catalysis constitutes a useful synthetic method. Most boronic acids are terminally stable compounds, resistant to air and humidity, compatible with many functional groups readily attacked by con- ventional organometallic reagents, and have low toxicity. In addi- tion, a large number of them are nowadays commercially available, and can also be prepared by various synthetic routes. 2 However, the direct conjugate addition of boronic acids is pre- cluded by their low nucleophilicity, and some kind of activation is normally required. This can be achieved by transmetalation to transition metals, mainly Rh and Pd, in catalytic cycles. 3,4 Although less developed, this type of reaction can also be promoted by or- ganic molecules, either stoichiometrically 5 or catalytically. 6 In the search for new reagents that allow the activation of boro- nic acids catalytically toward the conjugate addition to simple a,b- unsaturated ketones under metal-free mild reaction conditions, we have focussed our attention on acylation reagents. The interaction of boronic acids with this type of reagents (Scheme 1) leads to the in situ formation of mono or diacylboronates A, where the Lewis acidity of the boron atom is enhanced with respect to the starting boronic acid. 7 This may permit coordination of boron to the lone electron-pair of the carbonyl oxygen, thus facilitating the transfer of the nucleophilic carbon backbone in an intramolecular fashion. 8 We began our research by exploring different acylation reagents in the conjugate addition of chalcone 2a with 2-phenylvinylboron- ic acid 1a. These results are gathered in Table 1. We observed that reaction in the presence of Ac 2 O, either in cat- alytic or stoichiometric amounts (Table 1, entries 1 and 2), led to the formation of the conjugate addition product 3a in a low yield. However, the use of Ac 2 O as the solvent at 60 °C permitted the syn- thesis of 3a in a higher yield (Table 1, entry 3). When the reaction was carried out using AcCl as the promoter, we observed again a 0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2012.06.105 ⇑ Corresponding author. Tel./fax: +34 91 394 3253. E-mail address: csaky@quim.ucm.es (A.G. Csákÿ). R 1 B(OH) 2 + 1 2 RCOX R 1 B Y Y A X = Cl, OCOR, Y = OH, OCOR R 2 R 3 O R 3 R 2 O B R 1 Y Y + - B R 2 O R 3 R 1 B R 2 O R 3 R 1 C 3 H + Y Y Scheme 1. Activation of boronic acids toward conjugate addition. Tetrahedron Letters 53 (2012) 4721–4724 Contents lists available at SciVerse ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet