Asymmetric Catalysis DOI: 10.1002/ange.201007727 Rhodium-Catalyzed Asymmetric Formal Olefination or Cycloaddition: 1,3-Dicarbonyl Compounds Reacting with 1,6-Diynes or 1,6-Enynes** Takeshi Suda, Keiichi Noguchi, and Ken Tanaka* Transition-metal-catalyzed asymmetric hydrogenation of enolizable b-ketoesters leading to b-hydroxyesters is a useful method for the one-step construction of two consec- utive stereocenters. [1–3] In this reaction, the ketone carbonyl group is enantioselectively reduced with hydrogen through C À H/O À H bond formation (Scheme 1). In contrast, asym- metric olefination or cycloaddition of the ketone carbonyl group of b-ketoesters through C =C or C ÀC/C ÀO bond formation would furnish chiral b,g-unsaturated esters or b- alkoxyesters in a single step (Scheme 1). [4] Despite potential synthetic utility of such reactions, no report has been found in the literature to date. In 2007 our research group reported that a cationic rhodium(I)/H 8 -binap complex [5, 6] is a highly active and versatile catalyst for the [2+2+2] cycloaddition [7] of 1,2-dicarbonyl compounds with 1,6-diynes. [8–12] After this report, we succeeded using the cationic rhodium(I)/H 8 -binap complex as a catalyst in the asymmetric [2+2+2] cyclo- addition of 1,2-dicarbonyl compounds with 1,6-enynes, thereby constructing two stereocenters with high enantio- and diastereoselectivity. [13, 14] We report herein the cationic rhodium(I)/H 8 -binap or segphos complex as a catalyst for the asymmetric formal olefination and cycloaddition of 1,3- dicarbonyl compounds with 1,6-diynes and 1,6-enynes, respectively, which construct one or three stereocenters with high diastereo- and enantioselectivity. [15] We first investigated the reaction of b-ketoester 2a (1.1 equiv) with sulfonamide-linked 1,6-diyne 1a in the presence of a cationic rhodium(I)/(R)-binap complex (5 mol%). Gratifyingly, the reaction proceeded at room temperature for only 1 hour to give a-methyl-b,g-unsaturated ester 3aa with moderate yield and enantioselectivity presum- ably through [2+2+2] cycloaddition and subsequent electro- cyclic ring opening [16] (Table 1, entry 1). After screening biaryl bisphosphine ligands (entries 1–3), the use of (R)-segphos furnished 3aa with the highest ee value, but the yield was still moderate (entry 3). The use of excess 2a (2.0 equiv) in the reaction using (R)-segphos increased the product yield along with slight improvement of the product ee value (entry 4). Significant improvement of both the product yield and ee value using excess 2a was observed in the reaction using (R)-H 8 -binap, which furnished 3aa with the highest yield and ee value (entry 5). The absolute configuration of the major Scheme 1. Transition-metal-catalyzed asymmetric C ÀH/OÀH versus C =C or C ÀC/C ÀO bond-forming reactions of enolizable b-ketoesters. Table 1: Screening of ligands for rhodium-catalyzed asymmetric inter- molecular reaction of 1,6-diyne 1a and b-ketoester 2a. [a] Entry Ligand 2a [equiv] Yield [%] [b] (E/Z) ee [%] [c] 1 (R)-binap 1.1 69 (1:7) 61 (S) 2 (R)-H 8 -binap 1.1 66 (1:7) 70 (S) 3 (R)-segphos 1.1 61 (1:5) 92 (S) 4 (R)-segphos 2.0 83 (1:6) 94 (S) 5 (R)-H 8 -binap 2.0 97 (1:7) 96 (S) [a] In all entries, complete conversions of 1a were observed. [b] Yield of isolated product. [c] The ee value and absolute configuration of a major olefin geometric isomer. (R)-binap = (R)-2,2’-bis(diphenylphosphino)- 1,1’-binaphthyl, (R)-H 8 -binap = (R)-2,2’-bis(diphenylphosphino)- 5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-binaphthyl, cod = 1,5-cyclooctadiene, (R)-segphos = (R)-5,5’-bis(diphenylphosphino)-4,4’-bi-1,3-benzodioxole. [*] T. Suda, Prof.Dr. K. Tanaka Department of Applied Chemistry, Graduate School of Engineering Tokyo University of Agriculture and Technology Koganei, Tokyo 184-8588 (Japan) Fax: (+ 81) 42-388-7037 E-mail: tanaka-k@cc.tuat.ac.jp Homepage: http://www.tuat.ac.jp/ ~ tanaka-k/ Prof. Dr. K. Noguchi Instrumentation Analysis Center, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588(Japan) [**] This work was supported partly by Grants-in-Aid for Scientific Research (Nos. 20675002 and 20·8746) from MEXT (Japan). We are grateful to Takasago International Corporation for the gift of H 8 - binap, segphos, and xyl-segphos, and Umicore for generous support in supplying a rhodium complex. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201007727. Angewandte Chemie 4567 Angew. Chem. 2011, 123, 4567 –4571  2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim