1Efficient Synthesis of Cyclopentenones fromEnynyl Acetates via Tandem Au (I)-Catalyzed3,3-Rearrangement and the Nazarov Reaction*Liming Zhang & Shaozhong WangMatthew ParkerChemistry 2320 Journal ClubMonday, February 13, 2006Synthesis of CylopentenonesM. Parker - Chem 232012/13/062Classical Nazarov ReactionR1R2R3R4OR1R2R3R4OLA or HOR3R4R2R1Lewis Acid orProtic AcidLight (hv)Vorlander & Schroeter (1903)Nazarov (1940 & 1950)Conversion of Divinyl Ketones toCyclopentenones via pentadienylic cationMechanismR1R2R3R4OR1R2R3R4OHOR3R4R2R1H-HHOR3R4R2R1HOR3R4R2R1M. Parker - Chem 232022/13/063Summary of ProblemsStereochemistry of substituentsSource of proton lossLocation of double bond formation Silicon Groups will leave preferential inplace of a proton to direct double bondformationAccessibility of Starting MaterialsSummary of PositivesCan make highly substituted fusedbicyclic ring systemsA lot of synthetic versatility Cyclopentenones Attack by nucleophiles to formcyclopentanonesM. Parker - Chem 232032/13/064Synthesis of CylopentenonesO OR1R3R2OR1R3R2OOCR1R2R3Au (I)Au (I)3,3 RearrangementOOR1R3R2OOR1R2R3AuAuOOCR1R2R3Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804M. Parker - Chem 232042/13/065Nazarov CyclizationOAcCR1R2R3AuOAcR1R2R3AuOAcR2R3AuR1-HOAcR2R3AuR1OAcR2R3AuR11,2 HydrideShift+HHHOR2R3R1Reaction OptimizationEntry Catalyst Conditions Time (h) Conv. (%) 2 311% AuCl(PPh3)/AgSbF6dry CH2Cl2, rt0.5 >99 65 821% AuCl(PPh3)/AgSbF6wet CH2Cl2, rt0.5 >99 <1 9235% AuCl3dry CH2Cl2, rt0.5 48 31 <145% AuCl3wet CH2Cl2, rt0.5 96 5 645 5% PtCl2dry toluene, 80 C 4 41 32 <165% AgSbF6wet CH2Cl2, rt0.5 <1 <1 <17 5% TfOHdry CH2Cl2, rt0.5 62d<1 <1yield (%)M. Parker - Chem 232052/13/066Reaction ScopeReaction ScopeM. Parker - Chem 232062/13/067Reaction ScopeAspects of InnovationAu (I) versus Classical Nazarov Accessibility of complex structures isgreater Availability of diverse starting materials Greater control over double bondplacement Assisted by catalyst Conditions are mild Room temperature and modest pHM. Parker - Chem 232072/13/068Versatility of Propargyl EstersR HOR'OROPrepared from Aldehyde and EnynePrepared from Aldehyde, Acetylene, andAlkenyl HalideState-Of-The-Art AnalysisRaises the bar for catalysis Multitasking Metals Two different reactions mediated by a singlecatalysis Immunity to water Reaction is aided by the presence of waterM. Parker - Chem 232082/13/069Future OutlookApplication of this methodology tocomplex molecules Fused bicyclic systems-5,5; 5,6; 5,7 ringsystemsFurther examination of this catalysisReferencesZhang, L.; Wang, S. J. Am. Chem. Soc.2006, 128, 1442.Zhang, L. J. Am. Chem. Soc. 2005, 127,16804.Kurti, L.; Czako, B. Strategic Applications ofNamed Reactions in Organic Chemistry;Elsevier Academic Press: Burlington, MA,2005; pp 304-305.M. Parker - Chem
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