title: Gold-catalyzed cycloisomerization of 1,7-enyne esters to structurally diverse cis-1,2,3,6-tetrahydropyridin-4-yl ketones.
abstract: A synthetic method that relies on gold(I)-catalyzed cycloisomerization of 1,7-enyne esters to prepare highly functionalized cis-1,2,3,6-tetrahydropyridin-4-yl ketone derivatives in good to excellent yields and as a single regio-, diastereo-, and enantiomer is described. By taking advantage of the distinctive differences in the electronic and steric properties between an NHC (NHC = N-heterocyclic carbene) and phosphine ligand in the respective gold(I) complexes, a divergence in product selectivity was observed. In the presence of [PhCNAuIPr](+)SbF6(-) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidine) as the catalyst, tandem 1,3-acyloxy migration/6-exo-trig cyclization/1,5-acyl migration of the substrate was found to selectively occur to give the δ-diketone-substituted 1,2,3,6-tetrahydropyridine adduct. In contrast, reactions with the gold(I) phosphine complex [MeCNAu(JohnPhos)](+)SbF6(-) (JohnPhos = (1,1'-biphenyl-2-yl)-di-tert-butylphosphine) as the catalyst was discovered to result in preferential 1,3-acyloxy migration/6-exo-trig cyclization/hydrolysis of the 1,7-enyne ester and formation of the cis-1,2,3,6-tetrahydropyridin-4-yl ketone derivative. The utility of this piperidine forming strategy as a synthetic tool that makes use of 1,7-enyne esters was exemplified by its application to the synthesis of an enantiopure analogue of the bioactive 2,3,4,4a,5,9b-hexahydroindeno[1,2-c]pyridine family of compounds.
authors: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
authors: Weidong
authors: W
authors: Rao
authors: Sally
authors: Ming Joo
authors: MJ
authors: Koh
authors: Philip Wai Hong
authors: PW
authors: Chan
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D004952:Esters / Q000737:chemistry*; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D050607:Organogold Compounds / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D000480:Alkynes; D004952:Esters; D007659:Ketones; D050607:Organogold Compounds