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Sep. 5, Hydroacylation by Brandon Reinus Hydroacylation and Related Topics Dong Group Seminar Brandon Reinus Wed, Sept. 5th 2012 Why? ¡ Looking at the reaction, it is a highly atom- economical approach to synthesizing ketones ¡ Umpolung (ex: deprotonating dithioacetals) ¡ Using acrylate derivatives generates a 1,4 diketone relationship, a hard relationship to establish using classical organic synthesis. Presentation Overview 1. Hydroformylation (extremely brief) 2. Rh-Catalyzed Hydroacylation ¡ Intramolecular ¡ Intermolecular ¡ Other 3. NHC Catalyzed Hydroacylation ¡ Benzoin reaction ¡ Stetter reaction ¡ other Part 1 : Background Reppe Roelen Science of Synthesis, Stereoselective Synthesis 1, 2011, pg.409 Hydroformylation Metal-Organic Cooperative Catalysis Park et al. Introduction SCHEME 2 Among the many elegant examples of transition metal cat- alyzed activation of C-HandC-Cbonds,1 chelation-as- sisted protocols have recently attracted increasing attention in organometallic chemistry. Directed metalation processes have been demonstrated by valuable applications in organic synthesis, showing remarkable efficiency and chemoselectivity.2 In general, a chelation-assisted proto- col facilitates the formation of either the kinetically or ther- modynamically favored five- or six-membered metallacycle; aprepositionedcoordinatinggroupinducesspatialproxim- ing decarbonylation, their structures are too specific to apply ity between the C-HorC-Cbondsandthetransitionmetal for common aldehydes. center.1,2 Despite the magnificent usefulness in activating otherwise stable C-HandC-Cbonds,amajordrawbackof the chelation-assisted protocol is the need for a coordina- (1) tion group in a substrate. As a consequence, this introduces the necessity of additional steps to remove the coordinat- ing groups, and the method often suffers from limitations in employing noncoordinating or weakly coordinating sub- (2) strates. In particular, the C-Hbondactivationprocessof aldehydes, a key step of hydroacylation of olefins, can be seriously hampered by the lack of a strong coordinating The turning point of general chelation-assisted hydroa- group in a substrate leading to more critical problems such cylation was realized from the example of hydroacylation as decarbonylation (Scheme 1).3 using aldimine made up of 2-amino-3-picoline (1)andben- Because the principal challenge associated with the C-H zaldehyde.7 There is a very important consideration in our bond cleavage of an aldehyde involves suppressing the focus on a metal-organic cooperative catalysis (MOCC). For decarbonylation process of the acyl-metal hydride spe- instance, if incorporation of a new catalytic cycle of aldi- cies, some catalyst systems under a high pressure of car- mine formation into the conventional hydroacylation of bon monoxide or ethylene gases have been devised to aldimine is possible, we anticipated that a general and stabilize acyl-metal hydride species.4 However, these sys- decarbonylation-free hydroacylation of olefins with a vari- tems are not general and efficient due to the harshness of ety of aldehydes could be devised (Scheme 2). the reaction conditions and limitation of the olefins that can Fascinated by the concept of MOCC, we have investigated be used. acatalyticsystemconsistingofatransitionmetalandan An alternative approach to stabilize the acyl-metal hydride organic catalyst as a new chelation-assisted hydroacylation species was inspired by the isolation of cyclometalated com- protocol. In the quest for an optimized system composed of a 5 plexes derived from 8-quinolinecarboxaldehyde (eq 1) and Wilkinson’s catalyst, (Ph3P)3RhCl (2)and1,wefoundthatcom- 2-(diphenylphosphanyl)benzaldehyde6 (eq 2), which were a mon aldehydes can be successfully applied in this transfor- milestone of chelation-assistedPart hydroacylation. 2 : Rh-Catalyzed Although it is mation. 8 In addition, surprising efficiency enhancements could apparent that these aldehydesHydroacylation were very effective in avoid- be achieved when benzoic acid and aniline were introduced SCHEME 1 More on Decarbonylation: Organometallics 1999, 18, 5311 Adv. Synth. Catal. 2006, 348, 2148 JACS 2008, 130, 5206 Chem. Commun. 2008, 6215 Decarbonylation can be surpressedVol. by 41, using No. 2 highFebruary pressures 2008 222-234 of ethyleneACCOUNTS OF CHEMICAL RESEARCH 223 or CO or by generating a metallacycle Accounts of Chemical Research p222, 2008 726 Chemical Reviews, 2010, Vol. 110, No. 2 Willis Scheme 1 Scheme 4 Scheme 5 Scheme 2 Scheme 6 Historical Reactions Scheme 3 726 Chemical Reviews, 2010, Vol. 110, No. 2 ¡ Sakai (1972) Willis which the acyl unit is positioned trans to the chloride ligand (Scheme 4).8 The stability of complex 5 is due to the slow Scheme 1 Scheme 4 dissociation of the trimethylphosphine ligands.9 Heating 726726 ChemicalChemical Reviews, Reviews, 2010, 2010, Vol. Vol. 110, 110, No. No. 2 2 WillisWillis complex 5 to 50 °Cresultedinintramolecularhydroacylation to provide cyclopentanone in 72% yield. An experiment SchemeScheme 1 1 ¡ Milstein (1982)SchemeScheme 4 4 using a catalytic amount of complex 5 achieved three synthetically useful methods based on this reaction are turnovers; although only a low number of turnovers were known.4 In general, the most significant advances in hydroa- achieved,*Trimethyl this represented the first example of catalysis that cylation chemistry have involved developing strategies, or didphosphine not rely onis slow the presence of ethylene (for example, see Schememethods, 5 to limit this undesired decarbonylation pathway. Schemeto dissociate 5). ¡ Miller and Coworkers (1976) SchemeSchemeThe review 5 5 is divided according to the transformation Scheme 2 being considered, that is, intramolecular alkene hydroacy- 2.2.*Also Catalytic isolated Systems ethylene insertion lation, intermolecular alkene hydroacylation, etc., and when 2.2.1. Cyclopentanone Synthesis SchemeScheme 2 2 needed also by catalyst type. During these sections, detailed products mechanistic arguments relevant to the key hydroacylation Miller and co-workers demonstrated that intramolecular ¡ Larock (1980) Schemestep 6 will not be presented; rather, these are collected together alkene hydroacylation could be performed using substo- SchemeSchemein section 6 6 6. The scope of this review is comprehensive from ichiometric amounts of rhodium complexes if ethylene- the first report in 1972 through June 2009. A number of saturated solvent was employed. 4-Pentenal could be cyclized reviews that deal with C-H activation cover some aspects to provide cyclopentanone in 72% yield using only 10 mol of hydroacylation,1 as do several metal-specific reviews;5 %Wilkinson’scomplexinethylenesaturatedchloroform however, a comprehensive treatment that covers all substrate (Scheme 5).10 Several products originating from intermo- types and all catalyst systems has yet to appear.6 Reactions lecular reaction of ethylene and pentenal were isolated in that generate acyl metal intermediates similar to 1 indirectly Chemicallow yieldReviews, (see 2010, Scheme p. 725 32).11,12 via simple carbonylation or carbonylation-type reactions are Larock observed a similar improvement in the efficiency not considered.7 of a range of intramolecular hydroacylation reactions upon the use of ethylene saturated solvent. In a departure from 2. Intramolecular Alkene Hydroacylation the Miller system, he found that catalysts generated in situ Scheme 3 from [Rh(COD)Cl]2 and P(4-MeC6H4)3,P(4-MeOC6H4)3,or Scheme 3 13 Scheme 3 which2.1. Stoichiometric the acyl unit is positioned Systemstrans to the chloride ligand P(4-Me2NC6H4)3 were most efficient. With the relatively which the acyl8 unit is positioned trans to the chloride ligand high catalyst loadings of 50 mol % in methylene chloride at (Scheme 4). 8The stability of complex 5 is due to the slow whichdissociation(Scheme theSakai acyl disclosed 4). unit ofThe is the positioned stability the trimethylphosphine first of exampletrans complexto of the5 ligands. ais metal-mediated chloride due9 toHeating the ligand slow room temperature, the method could be used for the synthesis hydroacylation8 reaction in a study on prostanoid synthesis.9 3 (Schemecomplexdissociation 4). 5Theto 50 of stability°Cresultedinintramolecularhydroacylation the trimethylphosphine of complex 5 is ligands. due to theHeating slow of a range of substituted, spirocyclic, and fused cyclopen- dissociationtocomplexThe provide reactions of5 to cyclopentanone the 50 involved° trimethylphosphineCresultedinintramolecularhydroacylation treatment in 72% of a yield. range ligands. An of 4-enals experiment9 Heating with tanone products (Scheme 6). No other olefin or acetylene stoichiometric amounts of Wilkinson’s complex at room complexusingto5 provideto a 50 catalytic cyclopentanoneCresultedinintramolecularhydroacylation amount of in complex 72% yield.5 achieved An experiment three additive proved as effective. It was also reported that adding usingtemperature a catalytic° and delivered amount cyclopentanones of complex 53achievedin up to 34% three water had no effect on the reaction yield although the catalyst synthetically useful methods based on this reaction areto provideturnovers; cyclopentanone although only a in low 72% number yield. of turnovers An experiment were syntheticallyknown.4 In general, useful the methods most significant based on advances this reaction in hydroa- are achieved,turnovers;yield together this although representedwith similar only theamounts a low first number example of cyclopropane of of turnovers catalysis products that were was destroyed by the presence of oxygen.
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