One-pot cyclocondensation

Wu and Sun have presented a versatile procedure for the liquid-phase synthesis of 1,2, ,4-tctrahydro-/i-carbolines [77]. After successful esterification of the MeO-PEG-OH utilized with Fmoc-protected tryptophan, one-pot cyclocondensations with various ketones and aldehydes were performed under microwave irradiation (Scheme 7.68). The desired products were released from the soluble support in good yields and high purity. The interest in this particular scaffold is due to the fact that the l,2,3,4-tetrahydro-/f-carboline pharmacophore is known to be an important structural element in several natural alkaloids, and that the template possesses multiple sites for combinatorial modifications. The microwave-assisted liquid-phase protocol furnished purer products than homogeneous protocols and product isolation/ purification was certainly simplified. 

Substantial MW rate enhancements have been reported in the Biginelli synthesis of dihydropyrimidines [50, 51] under homogeneous conditions. The synthesis involves a one-pot cyclocondensation of a /i-ketoester with an aryl aldehyde and urea or thiourea in the presence of a catalytic amount of HC1 in ethanol solution. An example of this synthesis is shown in Scheme 4.17. 

Synthesis of tetrahydropyrido[2,3-,y pyrimidin-7-ones 537 in a microwave-assisted one-pot cyclocondensation of a,/3-unsaturated esters with active methylene compounds (malononitrile or methyl cyanoacetate) and amidine salts (guanidine or benzamidine) in NaOMe/MeOH for 10min has been reported <2003TL5385>. 

Patel and co-workers [61] have reported the microwave-assisted synthesis of a series of 3-(2,6-diphenyl-4-pyridyl)hydroquinolin-2-ones 10 by a one-pot cyclocondensation reaction under Krohnke s reaction conditions using 2-chloro-3-for-myl quinoline, an acetophenone and Al-phenacylpyridinum chloride in a mixture of ammonium acetate and acetic acid. Different kinds of substituents on the quinoline and acetophenone are well tolerated and most compounds 10 are obtained in high yield. This method allows the easy introduction of various substituents in the 2-, 4- and 6-positions of the pyridine 10 (Scheme 10). 

Sauzem et al. [23] demonstrated that the 5-trifluoromethyl-4,5-dihydro-lH-pyrazole scaffold (xxii) behaves like benzene bioisosteres, supplying novel analgesic and anti-inflammatory pyrazole derivatives. The target pyrazoles were obtained through a rapid one pot cyclocondensation reaction via microwave irradiation. 

Various benzimidazolyl spiro[mdole-thiazolidinones] (xxiii) have been synthesized following a three-component regioselective one-pot cyclocondensation strategy by Dandia et al. [30]. 

In a recent approach [66], 2,4,6-trisubstituted or 2-aminosubstituted pyridines 173/174 can be prepared in a one-pot cyclocondensation of methyl phosphonate anion with nitriles, aldehydes and enolates of methyl ketones or nitrile a-carbanions (followed by dehydrogenation) via in-situ generated a,p-unsaturated imines 172. 

Tetrahydro-p-carbolines, important structural elements of many tryptophan-derived natural alkaloids, showed a broad spectrum of pharmacological activities. One-pot cyclocondensation of polymer-bound tryptophan 399 with different aldehydes and ketones in CHCI3 in the presence of/>-toluenesulfonic acid (PTSA) as catalyst were carried out under MWI to give polymer-bound 1,2,3,4-tetrahydro-p-carboline derivatives within 15 min. Subsequent reaction with KCN in MeOH at room temperature gave 400 in 87-96% yields (Scheme 80). When cyclization was carried out under reflux in CHCI3 for 15 min using identical stoichiometry, no... 

The Biginelli reaction, that is, a one-pot cyclocondensation of aldehyde, 1,3-keto ester, and either urea or thiourea, is a useful multicomponent reaction which... 

Synthesis of 2-amino-7-methyl-5-oxo-4-aryl-4,5-dihydropyrano[4,3- ]pyran-3-carbonitriles (12) was reported in water medium in the presence or absence of catalyst as well from the one-pot cyclocondensation reaction between aromatic aldehydes, malononitrile (3), and 4-hydroxy-6-methylpyrone (11) (Scheme 6) [81,86]. 

Yan et al. (2007) reported that polysubstituted annulated pyridines can be synthesized in high yields by four-component, one-pot cyclocondensation reactions of N-phenacyl pyridinium bromide, aromatic aldehydes, acetophenones or cyclic ketones in the presence of ammonium acetate and acetic acid, assisted by microwave irradiation. Cyclic ketones with two a-CH groups yield annulated pyridines with additional a-benzylidene groups, which are derived in situ from double aldol condensation of cyclic ketones with two moles of aromatic aldehydes. 

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