Intramolecular condensation reactions reaction scheme

Lithium enolate 329 and a nitrile-furnished enamino ester 330, which on condensation with isocyanates/isothiocyanates gave N-3 substituted 331 (X = O, S) through a tandem nucleophilic addition-intramolecular aza-Michael reaction (Scheme 126) (09JFC1145). 

The preparation of thionan-5-one (143), in very poor yield, has been reported by the Dieckmann cyclization of 3-carboxyethylpropyl-4-carboxyethylbutyl sulfide <62JA2814>. The nine-membered aryl-fused rings (160) and (161) have been prepared by intramolecular condensation reactions between methyl ketones and methyl esters, using sodium hydride in boiling toluene (Scheme 14) <87CB1151>. 

Scheme 7.37 Enantioselective synthesis of 1,4-dihydropyridines by one-pot Michael/ enamine formation/intramolecular condensation reaction.

Scheme 7.73 Michael addition intramolecular condensation reaction.

Polymeranalogous reactions considered above may be referred to as intramolecular condensation transformations since they are accompanied by elimination of low-molecular products. On the other hand, PCSs can be obtained via polymeranalogous transformations, principally intramolecular polymerization reactions . Thermal and chemical cyclization of poly(acrilonitrile) (PAN) is an example of processes of this type. It was demonstrated by a number of researchers216-225 that thermal transformations of PAN follow the scheme ... 

The synthesis of highly substituted rigid tricyclic nitrogen heterocycles via a tandem four-component condensation (the Ugi reaction)/intramolecular Diels-Alder reaction was investigated in both solution and solid phase [24]. The Ugi reaction in MeOH (Scheme 4.2) involves the condensation of furylaldehydes 17, benzylamine 18, benzyl isocyanide 19 and maleic or fumaric acid derivatives 20, and provides the triene 21 which immediately undergoes an intramolecular Diels-Alder reaction, affording the cycloadduct 22 in a diastereoisomeric mixture with high yield. 

Recently, a new multicomponent condensation strategy for the stereocontrolled synthesis of polysubstituted tetrahydropyran derivatives was re-published by the Marko group, employing an ene reaction combined with an intramolecular Sakurai cyclization (IMSC) (Scheme 1.14) [14]. The initial step is an Et2AlCl-promoted ene reaction between allylsilane 1-50 and an aldehyde to afford the (Z)-homoallylic alcohol 1-51, with good control of the geometry of the double bond. Subsequent Lewis acid-media ted condensation of 1-51 with another equivalent of an aldehyde provided the polysubstituted exo-methylene tetrahydropyran 1-53 stereoselectively and... 

In the course of the first total synthesis of (+)-halichlorine <1999TL6513, 1999AGE3542>, the spiroquinolizidine unit 460 was constructed by a two-carbon chain extension in compound 458 through a crossed Claisen condensation, leading to 459, and an intramolecular Mannich reaction of this compound with formaldehyde (Scheme 109). 

The condensation reaction between a 1,3-oxazine 134 and 3-hydroxy-2,2-dimethylpropionaldehyde generates an intermediate product 135 which undergoes intramolecular cyclization via the Asinger reaction to give compound 136 (Scheme 16) <1995ZSK976>. 

Synthesis of acid 129 starts from the commercially available 6-heptenoic acid (122), which upon reaction with (4S)-benzyloxazolidin-2-one (123) as the chiral auxiliary group yields the intermediate 124, hydroxymethylation of which affords compound 125. Hydrolysis of compound 125 followed by condensation with O-benzylhydroxylamine gives rise to the hydroxamate (126), which is then converted into (Claclam 127 via an intramolecular Mitsunobu reaction. Hydrolysis of the (Claclam 127 affords acid 128, which is subsequently formylated at the benzyloxyamine moiety to give the required intermediate acid (129) in quantitative yield, as depicted in Scheme 26. 

A stereospecific intramolecular imino-ene reaction was used by Weinreb and co-workers92 to provide the enantio-selective total syntheses of (-)-montanine, (-)-coccinine, and (-)-pancracine. Refluxing the imine resulting from the condensation of 151 and 152 in mesitylene produces the amine 153 (Scheme 33) as a single stereoisomer in 63% yield after removal of the silyl group from the alkyne. The high stereoselectivity is thought to arise from a concerted ene process. 

Enantiopure quinolizidinones and indolizidinones were obtained by Ma and Zhu in an intramolecular conjugate addition of the secondary amine of 293 to the alkynoate ester to provide the intermediate allenoate 294, which was subsequently trapped in a condensation reaction to afford 295 (Scheme 19.53) [62], In some instances, intermediate 296 was isolated, which could also be converted to 295. This quinolizidinone intermediate was then converted in a concise manner to lasubine II (297). 

The limited extent of intramolecular rearrangements undergone by the chiral oxonium ions 35 and 36 at 720 torr and at 40 °C (Table 22) allows their use for probing the regio- and stereochemistry of the displacement reactions of Scheme 19. In this case, the allylic alcohol, precursor of the chiral oxonium ions 35 and 36, acts as the nucleophile NuH. The relevant results are condensed in Scheme 21. 

The proline-mediated intramolecular aldol condensation of dialdehyde substrates was also reported by List in 2003, affording enantioselective synthesis of cyclic p-hydroxy aldehydes via a 6-e ofexo-aldolization reaction (Scheme 11.7d). 

The aldol reaction can be applied to dicarbonyl compounds in which the two carbonyl groups are favorably disposed for intramolecular reaction. For formation of five- and six-membered rings, the use of a catalytic amount of a base is frequently satisfactory. With more complex structures, the special techniques required for directed aldol condensations are used. Scheme 2.9 illustrates intramolecular aldol condensations. 

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