Hydro-acyl-addition

Acylation of Activated Double Bonds and of Triple Bonds Hydro-acyl-addition... 

Addition of Alcohols, Amines, Carboxylic Esters, Aldehydes, etc. Hydro-acyl-addition, etc... 

In 1992, Sakai provided the first examples of highly enantioselective (>80% ee) hydro-acylations of olefins with aldehydes, the Rh(l)/BlNAP-catalyzed cyclization of 4-aUce-nals (Eq. 12) [14]. Additional work from the same laboratory established that certain 4-aryl-substituted substrates also undergo ring formation with good enantioselectivity... 

Intramolecular transition metal-catalyzed hydro acylation reactions have opened up a new area of synthesizing cyclic ketones. This reaction can also be extended to intermolecular addition reactions. Miller et al. found the first example of an intermolecular hydroacylation of an aldehyde with an olefin giving ketones, when they were studying the mechanism of the rhodium-catalyzed intramolecular cyclization of 4-pentenal using ethylene-saturated chloroform as the solvent (Eqs.46,50) [112]. 

Chelation-assisted additions of formyl C-H bonds to olefins and dienes have been reported by Jun et al. [120]. In the case of the reaction of 8-quinolinecar-boxaldehyde, they proposed that the formation of the stable 5-membered met-allacyclic complex [121] suppressed the undesired decarbonylation reaction (Eq. 53) [120]. The intermolecular hydro acylation of 1-alkene with 2-(diphenyl-phosphino)benzaldehyde by rhodium(I) catalyst has been conducted on the basis of this working hypothesis [122]. 

Yang et al reeently reported on the meehanism of 4-chlorobenzoyl eoenzyme A dehalogenase, an enzyme that catalyzes the hydrolytic dehalogenation of 4-chlo-robenzoyl coenzyme A (4-CBA-CoA) to form 4-hydro-xybenzoyl coenzyme A (4-HBA-CoA). The mechanism involves attack of an active site carboxylate at C4 of the substrate benzoyl ring to form a Meisenheimer complex (shown above). Loss of chloride ion from this intermediate then forms an arylated enzyme intermediate that is hydrolyzed to free enzyme plus 4-HBA-CoA by the addition of water at the acyl carbon. In later work, Taylor et al examined the activation of the 4-CB A-CoA toward nucleophilic attack by the active site carboxylate group. 

Carbonylation (the addition of carbon monoxide to organic molecules) is an important industrial process as carbon monoxide is a convenient one-carbon feedstock and the resulting metal-acyl complexes can be converted into aldehydes, acids, and their derivatives. The 0X0 process is the hydro-formylation of alkenes such as propene and uses two migratory insertions to make higher value aldehydes. Though a mixture is formed this is acceptable from very cheap starting materials. 

Anhydrides may also be employed instead of an acid chloride. The mixed anhydride of acetic and formic acid reacts with 1-iV-morpholinocyclohexene to give 2-hydro-xymethylenecyclohexanone . Acylation of isobutyraldehyde enamines with trichloroacetic anhydride in tetrahydrofuran at room temperature gives the a-trichloromethyl-j5-trichloroacetyl adduct . This occurs by initial ) -acylation to give the acyl iminium trichloroacetate, followed by decarboxylation and nucleophilic addition of the tri-chloromethyl anion to the iminium group. Trifluoroacetic anhydride under the same conditions just gave the -trifluoroacetyl derivative . 

The present results suggest a ready means for catalytic alcohol formation via carbene-like bihapto formyl and acyl species (e.g., equations (18) and (19)). Precedent exists for the alkoxide formation step of equation (19) (47,48,82,83). Chain growth could occur via the insertion of an unsaturated surface site into a H3C-0M(or R-OM) bond (an oxidative addition) to yield a metal-carbon bond, followed by further carbonylation, as illustrated in equations (20) and (21). There is good precedent for the insertion of metal ions into carbon-oxygen bonds (84,85,86). Hydro-... 

Quinoline, Isoquinoline, and their Benzo- and Hydro-derivatives. - Relatively few syntheses of quinolines are based on 2,3-disubstituted pyridines a recent addition to their number is illustrated in Scheme 33. The essential steps are Michael addition, intramolecular acylation, and aromatization via loss of toluene-p-sulphenic acid. ... 

Note-. These acylcinnolines have been made by primary synthesis (see Chapter 1), Reissert-type addition to cinnoline (Section 2.1.3), oxidation of alkylcin-nolines (Section 2.2.2), displacement of halogeno substituents (Section 3.2), hydrolysis of dihalogenomethylcinnolines (Section 3.2), N-acylation of tautomeric cinnolinones (Section 4.1.2.2), oxidation of extranuclear hydro-xycinnolines (Section 4.2), or as illustrated here. 

Conjugate addition products 322 and 323 have been subjected to hydro-genolysis in the presence of 10% Pd/C catalyst (Scheme 4.103). " 3-Substituted coumarins 324 were obtained in 50-66% yields from substrates 322 through fission of the benzyl ether and spontaneous cyclization via acyl substitution. Using compounds 323 as substrates, piperidinyl derivatives 325 were obtained in 45-61% yields, and the de-aminated derivatives 326 were also acquired in 9-21% yields. Such a synthetic method may enable the synthesis of multi-substituted coumarins (2//-l-benzopyran-2-ones), which are widely distributed in nature and many of which exhibit pharmacological activities. 

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