C À O Activation DOI: 10.1002/anie.201005767 Insertion of an Alkene into an Ester: Intramolecular Oxyacylation Reaction of Alkenes through Acyl C À O Bond Activation** Giang T. Hoang, Venkata Jaganmohan Reddy, Huy H. K. Nguyen, and Christopher J. Douglas* b-Alkoxyketones are common intermediates in organic syn- thesis. An unusual approach to this class of compounds could be the insertion of a C =C bond into an ester, a potentially atom economical process (Scheme 1). This alkene “oxyacy- lation” could be an alternative to the aldol reaction. [1] Atom economy and ester manipulation, however, are rarely com- patible: esters usually fragment after reactions with nucleo- philes, or decarbonylate when activated with transition metals. [2] In the rare cases when the acyl C ÀO bond is activated and decarbonylation is suppressed, the acyl metal alkoxide complexes can undergo additional transforma- tions, [3, 4] but only with the expulsion of an alcohol (Scheme 2 a) [3b–f] or ketone (Scheme 2 b). [3a] We are aware of one example where acyl C ÀO activation provided products containing the original atoms: Ohes recent Pd-catalyzed nitrile insertion into an acyl C ÀO bond, followed by rearrangement (Scheme 2 c). [4] The challenge of productive acyl C À O bond activation is accentuated by the frequent reports of the reverse reaction : when acyl metal alkoxides are accessed by other means, they readily undergo reductive elimination to form esters. [5] We postulated that a chelating group would prevent decarbonylation by stabilizing the acyl metal complex, I. Our approach was akin to stoichiometric acyl C À O bond activa- tion strategies [6–8] in which metal chelating groups were used. [6] We employed quinoline as a chelating group based on our previous successes in acyl C ÀC bond activation. [9] We designed an intramolecular reaction to avoid problems with regioselectivity and to increase local concentrations of alkene. Activation of 1a to I, followed by migratory insertion and reductive elimination would provide 2a, containing a cyclic ether with a ketone in a 1,3-relationship and a new fully substituted carbon center. Here, we report the first example of alkene insertion into the acyl C À O bond of an ester. Beginning with 1a, we screened Rh complexes containing various counterions (Cl, BF 4 , OTf), with [Rh(cod) 2 ]OTf (cod = cyclooctadiene) pro- viding encouraging results (Table 1, entries 1–3). A by- product observed in our initial study was the phenol 3a, resulting from a formal hydrolysis of 1a, though attempts to rigorously exclude water did not decrease the formation of 3a. Switching to 1,2-dicholorethane as solvent, [Rh(cod) 2 ]BF 4 showed good conversion, but gave a 1:1 mixture of 2a :3a (Table 1, entries 4, 5). The addition of bidentate phosphine ligands, particularly dppp, was effective at maintaining high conversion. Using the [Rh(cod) 2 BF 4 ]/dppp catalyst system at higher temperature suppressed the formation of 3a (Table 1, entries 8–11). Using the conditions from Table 1, entry 11, we examined the scope of oxyacylation (Table 2). Both electron-donating and electron-withdrawing substituents on the aromatic linker gave products 2b–g in good yields (Table 2, entries 1–6), although longer reaction times were required for electron- Scheme 1. Alkene oxyacylation. Scheme 2. Processes involving acyl C ÀO activation. [*] G. T. Hoang, V. J. Reddy, H. H. K. Nguyen, [+] Prof. C. J. Douglas Department of Chemistry, University of Minnesota Twin Cities, 207 Pleasant St. SE, Minneapolis, MN 55455 (USA) Fax: (+ 1) 612-626-7541 E-mail: cdouglas@umn.edu [ + ] UMN Undergraduate Research, 2009–2010. [**] We acknowledge the donors of the ACS Petroleum Research Fund for partial support (47565-G1). We thank UMN (start-up funds), Prof. Gunda Georg for discussions, and Rosalind Douglas for assistance with this manuscript. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201005767. Communications 1882  2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2011, 50, 1882 –1884