Indium(I) Catalysis DOI: 10.1002/anie.200700899 Catalytic Activation of Pinacolyl Allylboronate with Indium(I): Development of a General Catalytic Allylboration of Ketones** Uwe Schneider and Shu ¯ Kobayashi* The discovery and development of new catalytic methods for efficient C À C bond formations is one of the most important tasks in synthetic organic chemistry. [1] In this context, the allylation of ketones [2] is among the most useful and challenging transformations in organic synthesis, as the resulting tertiary homoallylic alcohols have proved to be highly versatile intermediates and synthetic building blocks. [3] Typical protocols for the allylation of ketones involve the use of allylindium reagents generated in situ under Barbier-type conditions from allyl halides and a stoichiometric amount of indium(0) [4] or indium(I). [5] Catalytic methods that have been reported include various catalytic enantioselective allylstan- nations of ketones employing chiral indium(III) Lewis acids [6] and others. [7] However, the substrate scope for ketones is generally not satisfactory and furthermore these methods require the use of more than one equivalent of toxic stannanes, which is undesirable with respect to safety and environmental considerations. In recent years, significant advances in ketone allylation have been achieved through the development of catalytic (asymmetric) allylsilylations by using (chiral) copper(I) [8] or silver(I) [9] Lewis acids. [10] Most recently, very elegant, catalytic asymmetric allylborations catalyzed by chiral Lewis [11] or Brønsted [12] acids have also been reported. [13] However, with only a handful of exceptions, the substrate generality is limited and therefore a truly general catalytic allylation method for ketones remains to be developed. The chemistry of indium in its low oxidation state (I) [14] is an underexplored area, and only sporadic examples of its use as stoichiometric reagents have been reported. [15] To the best of our knowledge, a catalytic synthetic method involving the use of a “catalytic” amount of indium(I) is to date unknown. Nevertheless, it has been shown that, depending on the nature of the ligand by which it is coordinated, indium(I) can act as a Lewis acid [16] or Lewis base [17] owing to the presence of both free p orbitals and a lone pair of electrons. [18] Indeed, a recent report revealed that indium(I) as a s donor is able to form donor–acceptor complexes with electron acceptors such as boron derivatives. [17] On the basis of this concept involving two Group 13 elements, we hypothesized that indium(I) as a Lewis base catalyst might activate a Lewis acidic allylboro- nate through formation of a metal–metal bond, and that the bimetallic allylborate so generated might enhance nucleophi- licity towards electrophiles such as ketones. Herein we report the unprecedented catalytic activation of pinacolyl allylbor- onate with indium(I) and its application to the general catalytic allylboration of ketones. Our initial experiments were conducted with the reaction of acetophenone (1a) with pinacolyl allylboronate (2 ; 1.5 equiv) as model substrates in dry THF at 40 8C (Table 1). As the indium source, we employed a stoichiometric amount of commercially available indium(I) iodide, [19] which was selected for its higher stability compared with other indium(I) halides. As shown, the noncatalyzed reaction essentially did not proceed, with only a trace amount of product being formed even after 24h (Table 1, entry 1). Gratifyingly, however, the indium(I)-mediated transformation cleanly afforded the desired tertiary homoallylic alcohol 3a in quantitative yield (Table 1, entry 2). Next, we reduced the amount of catalyst to 50 mol% and then to 20 mol%, which provided, to our delight, the desired product in quantitative and 99% yields, Table 1: Examination of various indium catalysts in the allylation of acetophenone (1a) with pinacolyl allylboronate (2). Entry Indium cat. (x [mol%]) Yield [%] [a] 1 – trace 2 InI (100) quant. 3 InI (50) quant. 4 InI (20) 99 5 InI (10) 85 6 InI (5) 88 7 InI (1) 70 (99) [b] 8 In 0 (20) + InI 3 (10) quant. 9 In 0 (20) 4 10 InI 3 (10) 3 11 InCl (20) 65 12 InBr (20) 87 13 InOTf (20) 39 14 In(OTf) 3 (20) 16 [a] Yields after preparative thin-layer or flash chromatography (silica gel). B(pin): pinacolyl boronate; OTf: trifluoromethanesulfonate. [b] Concen- tration of 1 m in THF under otherwise identical conditions. [*] Dr. U. Schneider, Prof.Dr. S. Kobayashi Graduate School of Pharmaceutical Sciences The University of Tokyo The HFRE Division, ERATO, JST Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan) Fax: (+ 81)3-5684-0634 E-mail: skobayas@mol.f.u-tokyo.ac.jp [**] Financial support was provided by ERATO, Japan Science and Technology Agency (JST). Dr. Masaharu Ueno is acknowledged for stimulating discussions. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Angewandte Chemie 5909 Angew. Chem. Int. Ed. 2007, 46, 5909 –5912 # 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim