Phase transfer catalysis intramolecular reactions

Similar to the Pd-catalyzed pyrrole and thiophene annulations, an intramolecular Heck reaction of substrate 91 resulted in benzofuran 92 [80], Such an approach has become a popular means of synthesizing fused furans. Muratake et al. exploited the intramolecular Heck cyclization to establish the tricyclic core structure en route to the synthesis of a furan analog of duocarmycin SA, a potent cytotoxic antibiotic [81]. Under Jeffery s phase-transfer catalysis conditions, substrate 93 was converted to tricyclic derivatives 94 and 95 as an inseparable mixture (ca. 4 1) of two double bond isomers. 

In the synthesis of the -azaebumane series, an intramolecular heteroaryl Heck reaction was the major operation to realize the cyclization <95TL1491>. Under Jeffery s phase-transfer catalysis conditions, the -azaebumane skeleton 105 was prepared from bromopyridine 104. The migratory insertion occurs onto the C(2) position of the indole ring. 

FER CATALYSIS GENERAL ACID CATALYSIS GENERAL BASE CATALYSIS HOMOGENEOUS CATALYST HETEROGENEOUS CATALYST INTRAMOLECULAR CATALYSIS MICELLAR CATALYSIS Mich ALT IS-MeNTEN KINETICS PHASE-TRANSFER CATALYSIS PSEUDOCATALYSIS RATE OF REACTION SPECIFIC CATALYSIS. 

The Darzens reaction (tandem aldol-intramolecular cyclization sequence reaction) is a powerful complementary approach to epoxidation (see Chapter 5) that can be used for the synthesis of a,P-epoxy carbonyl and a,p-epoxysulfonyl compounds (Scheme 8.32). Currently, all catalytic asymmetric variants of the Darzens reactions are based on chiral phase-transfer catalysis using quaternary ammonium salts as catalysts. 

Examples of migratory insertion to aromatic rings also include the total syntheses of anhydrolycorine-7-one (217) [102] and the f-azaebutnane series [103]. As illustrated in Scheme 38, an intramolecular Heck reaction of Af-acylindoline 216 installed the six-membered lactam in anhydrolycorine-7-one (217). In a similar process, the tetracyclic pyrido-[2 ,3 -prepared from bromopyridine 218 under phase-transfer catalysis conditions. Pyridyl indole 219 is a precursor of the pentacyclic skeleton of the E-azaeburnane series. 

Enantioselective phase-transfer catalysis has also been successfiilly applied to intramolecular aza-Michael reactions, as elegantly exemplified by Bandini and Umani-Ronchi in the reaction of amide tethered indolyl a,p-unsaturated esters to yield 3,4-dihydropyrazino[l,2-a]-indol-l(2/i)-ones [109]. With the general assumption that the annulation reaction proceeds to give products with (5) configuration, a proposal for the transition state of the enantioselective step of the reaction was made by the same group two years later [110]. In this transition step a favorable ir-stacking interaction between the indole and the benzyl-CF3 groups was postulated (Scheme 11.30). 

Cyclopropanecarboxylic esters have been prepared, in 75—86 % yield, by intramolecular alkylation of 4-chloroalkyl esters, using phase-transfer catalysis. Monoalkylation of nitro-alkenes by acrylic esters occurs in a controlled manner if a two-phase system is used, to give products of Michael addition in 45—65 % yield for five examples. An interesting variant on this reaction involves the generation of the a-nitro-carbanion by conjugate reduction of a nitroalkene with sodium borohydride followed by its conjugate addition to methyl acrylate yields of 62—95% are reported for five cases (Scheme 39). ... 

Scheme 7.5 Asymmetric intramolecular CDC reaction of THIQs under PA phase-transfer catalysis.

This chapter compares the reaction of gas-phase methylation of phenol with methanol in basic and in acid catalysis, with the aim of investigating how the transformations occurring on methanol affect the catalytic performance and the reaction mechanism. It is proposed that with the basic catalyst, Mg/Fe/0, the tme alkylating agent is formaldehyde, obtained by dehydrogenation of methanol. Formaldehyde reacts with phenol to yield salicyl alcohol, which rapidly dehydrogenates to salicyladehyde. The latter was isolated in tests made by feeding directly a formalin/phenol aqueous solution. Salicylaldehyde then transforms to o-cresol, the main product of the basic-catalyzed methylation of phenol, likely by means of an intramolecular H-transfer with formaldehyde. With an acid catalyst, H-mordenite, the main products were anisole and cresols moreover, methanol was transformed to alkylaromatics. 

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