Alkenes heterocyclic synthesis

The electrophile-induced cyclization of heteroatom nucleophiles onto an adjacent alkene function is a common strategy in heterocycle synthesis (319,320) and has been extended to electrophile-assisted nitrone generation (Scheme 1.62). The formation of a cyclic cationic species 296 from the reaction of an electrophile (E ), such as a halogen, with an alkene is well known and can be used to N-alkylate an oxime and so generate a nitrone (297). Thus, electrophile-promoted oxime-alkene reactions can occur at room temperature rather than under thermolysis as is common with 1,3-APT reactions. The induction of the addition of oximes to alkenes has been performed in an intramolecular sense with A-bromosuccinimide (NBS) (321-323), A-iodosuccinimide (NIS) (321), h (321,322), and ICl (321) for subsequent cycloaddition reactions of the cyclic nitrones with alkenes and alkynes. 

Dehydrochlorination of pentachlorocyclopropane, formed from trichloroethylene and sodium trichloroacetate as a source of dichlorocarbene, yields tetrachloro-cyclopropene [150], a particularly versatile reagent for various applications. It is a reasonably reactive dienophile [151], a reagent applicable to heterocyclic synthesis [152], and an electrophile for aromatic substitutions [153] and additions to alkenes [154] in the presence of Lewis acids. 

Pyridyldimethylsilane 24 is a reagent for the metal-catalyzed hydrosilylation of alkynes and alkenes <2004EROS1>. 4-(Trifluoromethyl)pyridine 25 has been used as a building block in heterocycle synthesis <2005EROS1>. 

Heterocycles can be prepared from selenium-induced cyclizations of urethanes, thioesters and alkenes. These cyclizations are seen infrequently, but have much potential in heterocyclic synthesis. The aniline (37) was treated with benzeneselenenyl chloride and silica gel (to facilitate the ring closure) to produce the hexahydrocarbazole (38) in good yield (equation 30). Sulto heterocycles are prepared similarly to nitrogen heterocycles. ... 

Padwa and coworkers found that a-cyanoaminosilane 12a is a convenient synthon for azomethine ylide 15 which is extensively used in heterocyclic synthesis [7]. AgP has been adopted to generate the ylide 15 from 12a for the preparation of pyrrolidine derivative 14 (Sch. 4). Various dipolarophiles including A-phenylmaleimide (13) can be used for the cycloaddition. When iV-[(trimethylsilyl)methyl]-substituted indole 16 is reacted with AgP in the presence of maleimide 13, pyrrolo[l,2-a]indole 17 is formed in good yield, retaining the CN group [8]. A silver-bonded carbonium ion is assumed to be a reactive intermediate. Reaction of a cyano-substituted azomethine ylide, derived from (silylmethylamino)malononitrile 12b and AgP, with methyl propiolate (18) provides 3-carbomethoxy-A-benzylpyrrole (19) [9]. Epibatidine, a novel alkaloid, was successfully synthesized by employing the [3 + 2] cycloaddition of azomethine ylide with electron-deficient alkenes as a key step [10]. 

M. A. P. Martins 4-Alkoxy-l,14-trichloro-3-alken-2-ones Preparation and applications in heterocyclic synthesis 2004CSY391... 

Topics of relevance to the content of this chapter which have been reviewed during the year include photoactive [2]rotaxanes and [2]catenanes, photochemical synthesis of macrocycles, phototransformations of phthalimido amino acids, photoaddition reactions of amines with aryl alkenes and arenes, photoreactions between arenenitriles and benzylic donors, photostability of drugs, polycyclic heterocycles from aryl- and heteroaryl-2-propenoic acids, photoreactions of pyrroles, photoamination reactions in heterocyclic synthesis, switching of chirality by light, photochromic diarylethenes for molecular photoionics and solid state bimolecular photoreactions. 

Vinylsilanes 132 have been reacted with bromomalononitrile to yield the intermediate 133, which was used for the synthesis of cyclopropane derivatives Addition reactions of dichloromalononitrile with substituted alkenes and alkadienes can also be used for the preparation of intermediates in carbo- and heterocyclic synthesis. 2-Arylmalononitriles 135 have been produced by coupling malononitriles with aryllead(IV) triacetates like 134163. 

The Pauson-Khand reaction provides another new approach to the metal-catalyzed synthesis of heterocycles. This reaction involves the interaction of the multiple bonds of an alkyne with an alkene and carbon monoxide in the presence of dicobalt octacarbonyl (Co2(CO)g), or with just this reagent as a source of CO. The overall process has been described as a [2 -h 2 -h 1] cycloaddition. Only a few applications to heterocyclic synthesis have been reported so far. A 2008 paper that is illustrative of the process describes the use of this reaction for the construction of a heterocyclic ring that is part of an azabicy-clo[3.3.1]nonane derivative. This ring system is present in the alkaloid (-)-alstonerine (4.37), which prompted this study. 

Alkylidenephosphoranes (a.La. phosphorus yUdes) of the general formula Ph3P=CR R (1) have been frequently used in key steps of heterocycle synthesis. Numerous papers and review articles [1-4] testify their versatility in the construction of rings with sizes ranging from three to well beyond 20 and with virtually any number, kind and distribution of heteroatoms. The Wittig alkenation of carbonyl groups is doubtless the most common, though not the only, reaction of P-ylides that has been employed in the cyclization of bifunctional precursors. The cycloaddition between acyl ylides (1 = H,... 

Several transformations involving CO insertion into a Pd-heteroatom bond have been developed that lead to incorporation of two molecules of CO into the heterocyclic product. This approach to heterocycle synthesis is exemplified by a synthesis of dihydroindolones reported by Gabriele [101]. As shown below, treatment of ortho-alkynyl aniline 157 with a Pd catalyst under CO in methanol afforded 158 in 50% yield (Eq. (1.62)). A similar strategy has been employed for the conversion of alkene 159 to pyrrolidinone 160 (Eq. (1.63)) [102]. 

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