Ketones cyclization, catalysts

Anhydrous iron(III) halides catalyse coupling of alkynes and aldehydes.211 Simple terminal alkynes, R CH, react with aldehydes, R2CHO, to give ( ,Z)-1,5-dihalo-1,4-dienes (55). In contrast, non-terminal arylalkynes give ( ,)-o, /3-unsaturated ketones. The catalysts also promote standard Prins cyclization of homoallylic alcohols. Studies of intermediates and of alkyne hydration - together with calculations - all support FeX3 complex formation with alkyne as the activating step. 

Acylations by a,3-unsaturated acyl halides provide routes to a,3,a, 3 -unsaturated ketones. Care must be taken in choice of reaction conditions, since Lewis acids are excellent catalysts for Nazarov cy-clizations to cyclopentenones (Scheme 2). Indeed, this can be exploited as a synthesis of the five-mem-bered ketones without isolation of the intermediate divinylic ketones. Cyclizations are also observed after acylations of cyclohexenes with vinylacetyl chloride derivatives (equation The acylation-cycloalkylation sequence provides a complement for the Robinson annelation, since the carbonyl function is located adjacent to the bridgehead position. This potential has been realized in natural product syntheses. ... 

Haloallenyl ketones cyclization gives halofuranes via two competitive pathways depending on the catalyst (Scheme 34) [194]. Thus, more oxophilic Au(III) activates the carbonyl group leading to 3-halofurans by a 1,2-halogen shifts, whereas Au(I) selectively activates the terminal double bond of the allene to form 2-halofurans. 

Another issue of regioselectivity arises with meta-substituted arylhydrazones from which either 4- or 6-substitutcd indoles can be formed. Robinson has tabulated extensive data on this point[9]. A study comparing regioselectivity of cyclization as catalysed by HCl/EtOH and ZnClj was carried out for several m-substituted arylhydrazones of diethyl ketone[10]. The results given in Table 7.1 show some dependence on catalyst but mixtures are obtained under all conditions studied. 

The Fischer indole synthesis can be regarded as the cyclization of an arylhydrazone 1 of an aldehyde or ketone by treatment with acid catalyst or effected thermally to form the indole nucleus 2. ... 

Many aryhydrazones provide two or more isomers when subjected to the conditions of the Fischer indole cyclization. The product ratio and the direction of indolization can also be affected by different reaction conditions (i.e. catalysts and solvents), which is attributed, at least in part, to the relative stabilities of the two possible tautomeric ene-hydrazine intermediates. Generally, strongly acidic conditions favor formation of the least substituted ene-hydrazine, while cyclization carried out in weak acids favors the most substituted ene-hydrazine. Eaton s acid (10% P2O5 in MeSOsH) has been demonstrated to be an effective catalyst for the preparation of 3-unsubstituted indoles from methyl ketones under strongly acidic conditions. Many comprehensive reviews on this topic have appeared. ... 

Alkylation lo yield a leriiary amine may occur easily if the formation involves cyclization (ii). Catalysts may have a marked influence. In reductive alkylation of ammonia wilh cyclohexanones, more primary amine was formed over Ru and Rh and more secondary amine over Pd and Pt. Reduction of the ketone to an alcohol is an important side reaction over ruthenium. 

The detailed mechanism of this enantioselective transformation remains under investigation.178 It is known that the acidic carboxylic group is crucial, and the cyclization is believed to occur via the enamine derived from the catalyst and the exocyclic ketone. A computational study suggested that the proton transfer occurs through a TS very similar to that described for the proline-catalyzed aldol reaction (see page 132).179... 

Perez-Pietro et al. have introduced the dirhodium complex (105) with a unique o/7/io-metalated arylphosphine ligand. The complex is an efficient catalyst for the cyclization of alkenyl diazo ketones (Scheme 7S).288 289... 

Addition of acyl anions generated from acylsilanes to a,(3-unsaturated ketones using N-heterocyclic carbenes (NHCs) derived from thiazolium salts as catalyst produced 1,4-diketones, which cyclized to form the corresponding furans in good yields under an acidic condition <06JOC5715>. 

The Skraup cyclization is another reaction principle that provides rapid access to the quinoline moiety. Theoclitou and Robinson have published the preparation of a 44-member library based on the 2,2,4-trisubstituted 1,2-dihydroquinoline scaffold by the Lewis acid-catalyzed cyclization of substituted anilines or aminoheterocyc-les with appropriate ketones (Scheme 6.237) [420], The best results were obtained using 10 mol% of scandium(III) triflate as a catalyst in acetonitrile as solvent at... 

Hydrative cyclization of diynes with ruthenium catalyst has been reported for the synthesis of sulfolenes or enones in aqueous medium.381 Reactions of unsymmetrical 1,6-diynes have been investigated, and some substrates are found to exhibit a directing effect of the ketone moiety in a pendant group. 

Recently, the silane-mediated reductive cyclization of activated alkynes with tethered ketones using Stryker s reagent as a catalyst was reported.112,90b Alkynyl ketone substrate 84a was treated with a catalytic amount of Stryker s reagent in the presence of polymethylhydrosiloxane (PMHS) to afford the cA-fused hydrindane 84b as a single diastereomer. This method is applicable to both five- and six-membered ring formation, but often suffers from competitive over-reduction of the reaction products (Scheme 59). 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

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