Cyclization, intermolecular

Bifunctional molecules undergo intermolecular cyclizations with enamines through simple alkylations 112-114) and acylations 115). For example, the reaction between l-(N-pyrrolidino)cyclopentene and 1,4-diiodobutane produces, after hydrolysis, ketospirans 92 and 93 113). 

The utility of base catalyzed condensations of esters to give jS-ketoesters is well known. A straightforward example of this reaction is the intermolecular cyclization of diethyl succinate giving 2,5-dicarbethoxy-l,4-cyclohexanedione, which can in turn be easily decarboxylated to give 1,4-cyclohexanedione. 

Intermolecular Cyclizations Involving Two Adjacent Halogeno Substituents... 

Reaction of vinyliminophosphoranes with aldehydes gives betaines which undergo either intra- or intermolecular cyclization to give pyridines 1 or dihydropyridines 2 in moderate yields <95TL(36)8283, 96JOC(61)8094>. 

The thermal, but not the photochemical, decomposition of ferro-cenylsulphonyl azide (14) in benzene gave some intermolecular aromatic substitution product FCSO2NHC6H5 (6.5%) but no intermolecular cyclization product (17). Contrariwise, photolysis of 14 in benzene gave 17 but no anilide 1 ). 

Many versatile approaches to the construction of fused heterocyclic systems (6 5 6) with ring junction heteroatoms have been reported. More general reactions which can be used for synthesis of derivatives of several tricyclic systems, and transformations which have potential for use in the preparation of a series of substituted compounds, are discussed in this section. Formation of the five-membered ring is presented first because it is a conceptually simple approach. It should be noted, however, that the addition of a fused six-membered ring to a bicyclic component offers much more versatility in the construction of a (6 5 6) system. Each subsection below starts with intramolecular cyclization of an isolated intermediate product. Reactions which follow are one-pot intermolecular cyclizations. 

This approach involves intermolecular cyclization of two six-membered heterocycles substituted with appropriate functional groups. Synthesis of 83 by the reaction between 2-aminopyridines and 3-ethoxycarbonyM-pipcridonc hydrochloride 82 in polyphosphoric acid is provided as an example (Equation 5) <1996T7789>. 

The intermolecular cyclization that involves the peri positions of unsubstituted systems (6 6) has been applied to the construction of fused (6 6 6) systems. An example of this approach is the reaction of bicyclic guanidine 123 with 1,3-dibromopropane furnishing the /wi-fused product 124 which can be isolated as tetrafluoroborate salt (Equation 12) C1996CB21, 1997TL1911>. 

Compound 133 was synthesized by the one-pot intermolecular cyclization of ketene aminal 132 with alkyl isothiocyanate (Equation 15) <1995BML1541, 1997BML651, 2002BMC1275>. 

A methodology described previously (Equation 11) has been successfully used to synthesize compounds 67 by intermolecular cyclization of acyclic tetraamine 137 with a-dicarbonyl reagents. This one-pot preparation furnishes... 

A few additional Pd-catalyzed schemes have been employed for Ilac type cyclization chemistry. Palladium-phenanthroline complexes were used by the Ragaini group to prepare indoles via the intermolecular cyclization of nitroarenes and alkynes in the presence of carbon monoxide <06JOC3748>. Jia and Zhu employed Pd-catalysis for the annulation of o-haloanilines with aldehydes <06JOC7826>. A one-pot Ugi/Heck reaction was employed in the preparation of polysubstituted indoles from a four-component reaction system of acrylic aldehydes, bromoanilines, acids, and isocyanides <06TL4683>. 

Intermolecular cyclization of allyloxycarbonylphosphines in the presence of azabisisobutyronitrile also results in the formation of heterocycles containing the P—C—O fragment (11) [Eq. (9)] (82ZN965). 

Allylation of aldehydes accompanying alkoxycarbonylation using cyclopentadienylmolybdenum complexes was also applied to butenolactone synthesis.246,247 Intra- and intermolecular cyclization occurred after allylation of the aldehyde to give a-methylene butenolactone derivatives (Scheme 59). 

Sonogashira reactions of both a-halothiophenes [117] and P-halothiophenes [118] proceed smoothly even for fairly complicated molecules as illustrated by the transformation of brotizolam (134) to alkyne 135 [119]. Interestingly, 3,4-bis(trimethylsilyl)thiophene (137), derived from the intermolecular cyclization of 4-phenylthiazole (136) and bis(trimethylsilyl)acetylene, underwent consecutive iodination and Sonogashira reaction to make 3,4-bisalkynylthiophenes [120], Therefore, a regiospecific mono-i/wo-iodination of 137 gave iodothiophene 138, which was coupled with phenylacetylene to afford alkynylthiophene 139. A second iodination and a Sonogashira reaction then provided the unsymmetrically substituted 3,4-bisalkynylthiophene 140. 

Two groups independently demonstrated that the strategy for the preparation of 55 could be used for the synthesis of 2-substituted-3-allenylbenzo[b]furans 59 (Scheme 3.31). The synthesis of 59 was achieved by intermolecular cyclization between alkynylphenols 56 and propargyl carbonates 57 [67] or by intramolecular rearrangement of (2-alkynylphenyl)propargyl ethers 58 [67, 68]. 

Dienes and polyenes can undergo a variety of intermolecular cyclization reactions, the exact nature of which is dependent on the number of double bonds, the relative positions of these bonds with respect to each other, the preferred conformation of the diene or polyene system and the reaction partner. 

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