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Abstract-A one-pot, tandem process has been developed for the efficient synthesis of functionalised carbocyclic amides. A substituted cyclopentenyl trichloroacetamide was synthesised using a tandem thermal aza-Claisen rearrangement and RCM process, while an analogous cyclohexenyl trichloroacetamide was generated with high diastereoselectivity using a tandem MOM-ether directed metal-catalysed aza-Claisen rearrangement and RCM process.Tandem and cascade reactions have emerged as powerful tools to perform several transformations in one synthetic operation rapidly increasing molecular complexity. In an effort to synthesise functionalised carbocyclic amides stereoselectively using a tandem process, it was proposed that this could be achieved by combining the etherdirected Overman rearrangement with a RCM reaction (Scheme 2). This communication describes the highly efficient synthesis of substrates 1 and 2 and the subsequent studies on the development of a tandem Overman rearrangement and RCM reaction for the one-pot synthesis of functionalised 5-and 6-membered carbocyclic amides.The allylic alcohol substrates 11 and 12, required for this study were synthesised in seven steps as shown in Scheme 3. (S)-Glycidol 3 was protected under standard conditions as the tert-butyldimethylsilyl ether. Regioselective ring opening of the epoxide using a copper-catalysed Grignard reaction with either vinylmagnesium bromide or allylmagnesium bromide gave adducts 5 and 6, respectively, both in high yields. Compounds 5 and 6 were converted to primary alcohols 7 and 8 by protection of the secondary alcohol with bromomethyl methyl ether followed by deprotection of the primary alcohol using TBAF. This allowed the one-pot Swern oxidation/HornerWadsworth-Emmons reaction of 7 and 8 to give α,β-unsaturated esters 9 and 10 in 99% and 94% yields, respectively. 14 Finally, DIBAL-H reduction of the esters completed the synthesis of allylic alcohols 11 and 12 in 68% and 78% overall yields, respectively.Development of a tandem ether-directed Overman rearrangement and RCM reaction was initially attempted using allylic trichloroacetimidate 1 which was prepared from allylic alcohol 11 using trichloroacetonitrile and DBU (Scheme 4). Surprisingly, treatment of 1 with bis(acetonitrile)palladium(II) chloride under standard conditions returned only starting material. Several other palladium(II) catalysts were also investigated giving the same result. 12b During the development of our original tandem process, the allylic acetimidate formed from (2E)-hepta-2,6-dien-1-ol was shown to rearrange in the presence of bis(acetonitrile)palladium(II) chloride in under 3 hours. 10The only difference in structure between this substrate and allylic trichloroacetimidate 1 is the MOM-ether group. This suggests that the MOM-ether may be coordinating to the palladium catalyst and directing it to the terminal alkene rather than the adjacent alkene 2 of the allylic trichloroacetimidate functional group. Such an intermediate would prevent the rearrangement from proceeding. A ta...

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Metathesis reactions O 0286Tandem aza-Claisen Rearrangement and Ring-Closing Metathesis Reactions: The Stereoselective Synthesis of Functionalized Carbocyclic Amides. -A novel tandem Mom-ether directed Overman rearrangement/ring-closing metathesis is developed to synthesize cycloalkenyl trichloroacetamides. -(SWIFT, M. D.; DONALDSON, A.; SUTHERLAND*, A.; Tetrahedron Lett. 50 (2009) 26, 3241-3244; Dep. Chem., Univ. Glasgow, Glasgow G12 8QQ, UK; Eng.) -Mais 40-045