Spiro-dehydration reaction

A The reaction is likely to proceed in a step-wise fashion, forming first a 3-hydroxyalkylindole. which then reacts again at C-3 to give a Spiro intermediate (Scheme 7.8). Migration of one of the substituents (they are, of course, identical so there is no preference) then gives a I,4-dihydroxy-l,2.3.4-tetrahydrocarbazole that dehydrates and aromatizes into the final product. 

Georgiev et al. [82] have described the preparation of novel adamantine-spiro-heterocyclic (3-lactams 34, 35, and 40. Grignard reaction of 2-adamantanone 31 with benzylmagnesium halide provided the compound 32, which on further dehydration afforded corresponding analogs 33. Condensation reaction of compound 33 with chlorosulfonyl isocyanate in ether afforded spiro-(3-lactams 34 and cycloaddition with chlorosulfonyl isocyanate resulted in the formation of spiro product 35 (Scheme 10). 

Reaction of thiochroman-3,4-diones with NaBH4 affords a mixture of the as- and trans- 3,4-diols and two keto alcohols result from reaction with MeMgl. Attempts to separate the latter mixture by preferential dehydration of the thiochroman-4-ol gave unchanged 3-hydroxythiochromanA-one, but no 4-methylenethiochroman-3-one was detected. Instead, a spiro-linked adduct arising from a hetero Diels-Alder cycloaddition between two molecules of the expected dehydration product was isolated (Scheme 102) <1994T7865>. 

These findings can be rationalised by consideration of a common intermediate. An intermediate carbinolamine could undergo either a nucleophilic substitution reaction, probably through an ionisation step facilitated by the high temperature and by assistance from the nitrogen lone pair to form the spiro compound in dimethylacetamide, or the intermediate may suffer dehydration in apolar solvents to form the corresponding isatin-3-imine. This imine can undergo facile syn-anti isomerisation upon protonation in acetic acid and thus yields the indoloquinoxaline derivative... 

Recently, an ultrasound-promoted synthesis of a series of medicinally relevant derivatives of the spiro[indole-thiazolidinone] ring system (compound 45) has been carried out from the three-component reaction of isatin, a 4-aminopyrazolin-3-one derivative and 2-mercaptopropionic acid in water, using cetyltrimethylammonium bromide (CTAB) as a phase-transfer catalyst (Scheme 1.20). This protocol avoided the need for either azeotropic removal of water or the use of a dehydrating agent, as required by conventional methods [28]. 

While the majority of relevant reactions of glycals discussed so far involve intermolecular processes, intramolecular examples are well established and very useful, the simplest involving attack of the 0-6 at C-1 so that when o-glucal itself is dehydrated, or when 3,4-di-O-substituted derivatives or compounds with silyl protection at 0-6 are treated with Lewis acids, they give 2,3-unsaturated 1,6-anhydrides of type 64 usually in high yield [98]. A related example involves the formation of the spiro compounds 65 which are produced on activation with N-iodosuccinimide of the appropriate glycal derivative possessing a... 

A four-component domino reaction of isatin 58, phenylhydrazine, 3-aminocrotononitrile 117, and cyclic 3-diketones/amide/thioamide 118 in an aqueous medium in the presence of ( )-camphor-10-sulfonic acid on heating at 100 °C for 2-3 h afforded the spiro-fused 2-oxindoles 119 (Scheme 39) [94]. The reaction was successfully extended to 5-chloro- and 5-nitroisatins. According to the proposed mechanism, an acid-catalyzed reaction of phenylhydrazine with nitrile 117 affords the 5-amino-3-methyl-l-phenyl pyrazole 111 that adds to the carbonyl carbon of isatin giving rise to an intermediate product 120. The acid-catalyzed reaction of this intermediate (that has been isolated) with carbonyl compounds 118 affords another intermediate compound 121, which eventually furnishes the final products 119 by cyclodehydration forming tetrahydropyridine ring followed by subsequent dehydration (Scheme 40). 

Intramolecular Cyclizations.—Base-induced 1,3-bonding occurs in the conversion of (24) into (25) even though the reaction is a 1,7-elimination. A spiro-product is also obtained in the dehydration of (26) with dicyclohexyl-carbodi-imide (DCQ. The mechanism of the 1,3-elimination from 3-phenyl-propyltrimethylammonium iodide with potassium amide in liquid ammonia has been investigated. The reaction is concurrent with 1,2-elimmation and shows a nitrogen kinetic isotope effect = 1.022 + 0.001). This and deuterium-... 

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