Cyclization, catalysts

The same methodology was extended to the synthesis of other condensed pyrrole derivatives too. N-Boc 2-amino-3-iodothiophene was alkylated with ethyl 4-bromocrotylate to give the A-crotyl derivative, which on treatment with a palladium-triphenylphosphine catalyst cyclized efficiently to the appropriate pyrrolo[2,3-6]thiophene (3.12.),16... 

Fig. 4. Dehydrocyclization of n-butylbenzene over 2% platinum on silica gel catalyst. (—) Cyclization to methylindan and methylindenes and (---) cyclization to naphthalene. According to Csicsery (13).

Macrocyclization. Trost and Warner17 have effected efficient cyclization to ten-and fifteen-membered rings by use of Pd(0) supported on a polystyrene bearing phosphine ligands. Precursors with an epoxy vinyl terminal group proved particularly suitable. Thus, 1 in the presence of such a Pd(0) catalyst cyclizes to 2 and 3 in 71% yield. The products are isomeric at the double bond, since both are oxidized to the ketone 4. The same catalyst system converted 1 (n = 9) into two macrocyclic isomers in 66% yield. Both cyclizations are concentration dependent. The temperature is also critical, the reaction being particularly clean at 65°. 

A study of the effect of the Michael acceptor configuration on the efficiency of intramolecular Morita-Baylis-Hillman reactions has been performed. Enones containing a pendant aldehyde moiety attached at the -position of the alkene group were employed as substrates and the reactions were catalysed by a phosphine. In all cases examined, with Ph3P as the catalyst, cyclization of (Z)-alkene (117) gave 2.5-8.5 times higher yield than with the E-isomer (115) under identical reaction conditions, both affording the same product (116). Steric effects are believed to be the source of this difference in reactivity.172... 

The precursor has the same carbon skeleton as the designated starting material. All that is necessary is to hydrogenate the double bond of the alkynoic acid to the cis alkene. This can be done by using the Lindlar catalyst. Cyclization of the hydroxy acid to the lactone is spontaneous. 

Yamamoto et al. [42] reported a highly enantioselective ene cyclization with a chiral zinc reagent as Lewis acid catalyst. Cyclization of 3-methylcitronellal 57 by at least 3 equiv. catalyst prepared in-situ from (i )-l,T-bi-2-naphthol (BINOL) 58 and Mc2Zn afforded the frans-cyclohexanol 59 in 86 % yield with 88 % ee as the sole product (Sch. 23). Reducing the amounts of the chiral zinc catalyst reduced both the chemical yield and the enantioselectivity. 

Condensation catalyst. Cyclization of 8-propionylphenylhydrazine to 3-methyl-oxindole is effected by heating it with either freshly ground calcium hydride or 40-mesh hydride supplied by Ventron. ... 

Diels-Alder condensation of acrolein followed by reduction affords a fairly good yield of 3,4-dihydro-2//-pyran-2-methanol (25) which, in the presence of acid catalysts, cyclizes to racemic 6,8-dioxabi-cyclo[3.2.1]octane, that is, l,6-anhydro-2,3,4-trideoxy-/8-DL-gZycero-hexopyranose323-326 (26). On reaction of 26 with bromine in carbon tetrachloride, a mixture of 2-bromo derivatives (27) is formed325-327... 

Other methodologies capable of cyclizing 1,6 dienes require the use of precious metals. Pd allyls cyclize these dienes to unsaturated products [117], and Ru and Rh catalysts cyclize heterocycle-substituted dienes [118]. Murai s method functions by the mechanism proposed in Scheme 1.13). 

While nickel catalysts cyclize 2,5-dimethyl-2,3,4-hexatriene to give octamethy/1-[4]-radialene, [CpCo(C2H4)2] under ethylene pressure gives a 1 1 codimerization product see equation (48). The [4]-radialene is rearranged by the catalyst to a benzene derivative, probably via cobalt 7r-allyl intermediates. ... 

A mixture of 400 mg. l-(3-aminobenzyl)-l,2,3,4-tetrahydro-6,7-dimethoxyisoquino-line, 36%-formaldehyde, and ethanol refluxed 1 hr. under Ng -> 340 mg. 11-amino-2,3-dimethoxy-5,6,13,13a-tetrahydro-8H-dibenzo[a,g]quinolizine. - An amino as well as a hydroxyl group promotes this reaction without acid catalyst. Cyclization occurs selectively at the position para to the amino group. F. e. s. S. Ishiwata and K. Itakura, Chem. Pharm. Bull. 18, 763 (1970). 

In addition, we have found that the stereochemistry of the Michael acceptor also plays an important role in the efficiency of phosphine-mediated intramolecular MBH reactions. In all examined cases with PPhs or polymer-supported phosphine as the catalyst, cyclization substrates enones 275 possessing (Z)-alkenes afforded the desired product 276 in a higher yield than ( )-275 under identical conditions (Scheme 1.99). The reason for this difference in reactivity is most likely steric in nature, as substrates where the p-substituent is ds to the electron-withdrawing substituent are more accessible to reaction with the nucleophilic catalyst than their trans counterparts. 

The A-acryloyl-o-bromoanilines (62) in the presence of a palladium catalyst cyclize to give the oxindole derivatives (63), no six-membered quinolone being produced. In attempting to favour ring closure to the six-membered product, the cyclization of a -substituted N-acryloyl-o-bromoaniline (64) was investigated, but the product was not the expected 3-substituted but the 4-substituted quinolone (65), which was obtained in 40% yield. "... 

Inactivated secondary alkyl- or arylsubstituted (pent-l-enyl)amines 10 undergo intramolecular hydroamination catalyzed, for example, by [IrClCOD]2 [234]. giving rise to pyrrolidines 9. With Pd-catalysts, cyclizing hydroamination is followed by an additional side-chain arylation ( 11) [235]. With systems of type 12, the Pd-catalyzed ring-closure proceeds with high stereoselectivity ( 13). 

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