Catalytic Asymmetric Rearrangement of Allylic Trichloroacetimidates. A Practical Method for Preparing Allylic Amines and Congeners of High Enantiomeric Purity Carolyn E. Anderson and Larry E. Overman* Department of Chemistry, 516 Rowland Hall, UniVersity of California, IrVine, California 92697-2025 Received July 5, 2003; E-mail: leoverma@uci.edu The rearrangement of allylic trichloroacetimidates to allylic trichloroacetamides (1 f 2), first reported in 1974, 1 is the preferred method for converting allylic alcohols to transposed allylic amines and their derivatives. 2 This transformation can be accomplished at elevated temperatures or at room temperature in the presence of catalysts such as Hg(OCOCF 3 ) 2 1 or PdCl 2 complexes. 3 Attempts to date to develop asymmetric Pd(II) catalysts for the rearrangement of prochiral allylic trichloroacetimidates have been unsuccessful, being plagued by competing elimination reactions, slow reaction rates, and low enantioselectivities. 4 The first two of these difficulties likely arise from competitive complexation of the small, basic trichloroacetimidate nitrogen to palladium. 5 Consequently, success in developing asymmetric Pd(II) catalysts for allylic imidate rearrangements has been realized only with N-arylimidates (3 f 4). 4,6 As coordination of an imidate nitrogen to a neutral palladium center should be less favorable than to a cationic Pd(II) complex, typically employed in asymmetric allylic imidate rearrangements, 4,6 the recent discovery that chloride-bridged dimer 5 7 is an excellent catalyst for asymmetric rearrangement of N-(p-methoxyphenyl)- trifluoroacetimidates 6f suggested that COP-Cl (5) might also catalyze allylic rearrangement of synthetically more important allylic trichloroacetimidates. In this Communication, we report that 5 is indeed an outstanding catalyst for transforming prochiral (E)-allylic trichloroacetimidates into allylic trichloroacetamides of high enan- tiopurity. The trichloroacetimidates employed in this study were prepared in 68-99% yield by DBU-catalyzed addition of allylic alcohols to trichloroacetonitrile. 8 Table 1 summarizes results obtained from catalytic rearrangements of nine representative primary allylic trichloroacetimidates with 5 mol % COP-Cl (5) in CH 2 Cl 2 (0.6 M) for 18 h. (E)-Allylic trichloroacetimidates containing unbranched R substituents at C3 rearranged within 18 h at room temperature to provide the corresponding (S)-allylic trichloroacetamides 2 in 92-96% ee and 80-85% yield (entries 1, 7, and 9); at 38 °C, yields of these rearrangements were improved (93-99%) with little or no erosion of enantioselection (entries 2 and 10). (E)-Allylic trichloroacetimidates containing i-Bu or cyclohexyl C3 substituents (1c and 1f) rearranged slowly at room temperature; however, at 38 °C these precursors provided the corresponding (S)-allylic trichlo- roacetamides 2c and 2f in 96% ee and high yield (entries 4 and 8). When the substrate concentration was increased to 1.2 M, a catalyst loading of only 1 mol % could be employed, as demonstrated by the formation of 2c in 92% yield and 98% ee (entry 5). The rearrangement was slowed drastically when R was t-Bu (entry 12). Also unreactive were (Z)-allylic trichloroacetimidates which gave the corresponding (R)-allylic trichloroacetamides 2 in poor yield and moderate enantioselectivity (entries 3 and 6). One additional limitation was identified: (E)-cinnamyl trichloroacetimidate 1h provided amide 2h in low yield with the major product resulting from formal [1,3]-rearrangement (entry 11). 9 The rearrangement of a series of (E)-allylic trichloroacetimidates containing various Lewis basic substituents was examined to explore the functional group compatibility of the COP-Cl-catalyzed reaction (Table 2). Oxygen functionality (including ester, acetal, ketone, and silyl ether) was well tolerated, with allylic trichloro- acetamide products being formed in 92-96% ee and excellent yield (entries 1-7). Trichloroacetimidate 1o containing a free hydroxyl group rearranged in high yield in the presence of COP-Cl (entry 8); however, enantioselection in this case was lower (80% ee). Nitrogen functionality proved more problematic. Substrate 1p containing carbamate functionality rearranged cleanly to give 2p in 95% ee (96% yield at 38 °C), as did trichloroacetimidate 1q containing a distal tertiary amine to provide 2q in 97% ee (82% yield at 23 °C). However, the allylic rearrangement was prevented, Table 1. Enantioselective Formation of Allylic Trichloroacetamides 2 from (E)- and (Z)-Allylic Trichloroacetimidates 1 a imidate amide entry cpds R E/Z temp (°C) yield (%) b % ee c /conf 1 a n-Pr E rt 80 94/S 2 a n-Pr E 38 °C 99 95/S 3 b n-Pr Z 38 °C 17 71/R 4 c i-Bu E 38 °C 95 96/S 5 c i-Bu E 38 °C d 92 98/S 6 d i-Bu Z 38 °C 8 73/R 7 e Me E rt 85 92/S 8 f Cy E 38 °C e 82 96/S 9 g CH2CH2Ph E rt 83 96/S 10 g CH2CH2Ph E 38 °C 93 93/S 11 h Ph E rt 13 nd f 12 i t-Bu E 38 °C 7 nd f a Conditions: 5 mol % catalyst 5, CH2Cl2 (0.6 M), 18 h. b Duplicate experiments ((3%). c Determined by HPLC analysis of duplicate experi- ments ((2%). d 1 mol % 5, CH2Cl2 (1.2 M). e CH2Cl2 (1.0 M). f nd ) not determined. Published on Web 09/19/2003 12412 9 J. AM. CHEM. SOC. 2003, 125, 12412-12413 10.1021/ja037086r CCC: $25.00 © 2003 American Chemical Society