Intramolecular Termination

As an application of this methodology to the syntheses of natural products, Sannicolo et al. have reported the preparation of benzazepine and tetra-hydroisoquinoline derivatives by silane-terminated intramolecular Heck reactions. These workers argued that one main disadvantage of the Heck reaction... 

The general procedure for a silane-terminated intramolecular enantioselective Heck reaction is exemplified by Scheme 3-60 [61a,b, 259]. A mixture of [Pd2(dba)3 - CHCI3] (0.025 mmol,... 

Li L, Liu L, Hong R, Robertson RL, Hastings JW. N-terminal intramolecularly conserved histidines of three domains in Gonylaulax luciferase are responsible for loss of activity in the alkaline region. Biochemistry 2001 40 1844-9. 

Scheme 3-5 Silane-terminated intramolecular Heck reaction [61].

Tietze, L.F. and Modi, A. (2000) Regioselective sUane-terminated intramolecular Heck reaction with alkenyl triflates and alkenyl iodides. Eur. J. Org. Chem., 1959-64. 

Tietze, L.E. and Schimpf, R. (1994) Regio- and enantioselective silane-terminated intramolecular Heck reactions. Angew. Chem., Int. Ed. Engl., 33,1089-91. 

Whereas the photochemical Nazarov cyclizations that are terminated through intermolecular nucleophilic attack typically give only modest yields of product, those that are terminated intramolecularly are highly efficient. West and co-workers have demonstrated trapping by a pendant hydroxyl group as indicated in Scheme 19.37. When methanol was used as the photolysis solvent instead of poorly nucleophilic trifluoroethanol, the yield of 141 dropped to 60%. A diastereomeric mixture of the methanol adducts to the epoxy zwitterion was also isolated in 14— 16% yield. Intramolecular trapping by electron-rich aryls and alkenes has also been demonstrated. 

The cyclization reactions discussed here either involve the intramolecular reaction of a donor group D with an acceptor group A or a cyclizing dimerization of two molecules with two terminal acceptors and two donors. A polymerization reaction will always compete with cyclization. For macrolides see p. 146 and p. 319 — 329. 

The TT-allylpalladiLim complexes formed as intermediates in the reaction of 1,3-dienes are trapped by soft carbon nucleophiles such as malonate, cyanoacctate, and malononitrile[ 177-179). The reaction of (o-iodophenyl-methyl) malonate (261) with 1,4-cyclohexadiene is terminated by the capture of malonate via Pd migration to form 262. The intramolecular reaction of 263 generates Tr-allylpalladium, which is trapped by malononitrile to give 264. o-[odophenylmalonate (265) adds to 1,4-cyciohexadiene to form a Tr-allylpalladium intermediate via elimination of H—Pd—X and its readdition, which is trapped intramolecularly with malonate to form 266)176]. 

The novel intramolecular reaction of the alkenyl bromide with the terminal alkyne in 328, followed by intramolecular Diels-Alder reaction, afforded the highly strained dynemicin A structure 329 in one stepf237]. 

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

The alkenylpalladium intermediate 364, formed by the intramolecular insertion of 363, is terminated by hydrogenolysis with formic acid to give the terminal alkene 365[266]. The intramolecular insertion of 366 is terminated by the reaction of the alkynylstannane 367 to afford the conjugated dienyne system 368[267j. 

The benzene derivative 409 is synthesized by the Pd-catalyzed reaction of the haloenyne 407 with alkynes. The intramolecular insertion of the internal alkyne, followed by the intermolecular coupling of the terminal alkyne using Pd(OAc)2, Ph3P, and Cul, affords the dienyne system 408, which cyclizes to the aromatic ring 409[281]. A similar cyclization of 410 with the terminal alkyne 411 to form benzene derivatives 412 and 413 without using Cul is explained by the successive intermolecular and intramolecuar insertions of the two triple bonds and the double bond[282]. The angularly bisannulated benzene derivative 415 is formed in one step by a totally intramolecular version of polycycli-zation of bromoenediyne 414[283,284],... 

The telomer 145 of nitroethane was used for the synthesis of recifeiolide (148)[121], The nitro group was converted into a hydroxy group via the ketone and the terminal double bond was converted into iodide to give 146. The ester 147 of phenythioacetic acid was prepared and its intramolecular alkylation afforded the 12-membered lactone, which was converted into recifeiolide (148),... 

The polymerization of ethyleneimine (16,354—357) is started by a catalyticaHy active reagent (H or a Lewis acid), which converts the ethyleneimine into a highly electrophilic initiator molecule. The initiator then reacts with nitrogen nucleophiles, such as the ethyleneimine monomer and the subsequendy formed oligomers, to produce a branched polymer, which contains primary, secondary, and tertiary nitrogen atoms in random ratios. Termination takes place by intramolecular macrocycle formation. 

Bis-Pyndoxal Tetraphosphate. A second class of bifunctional reagents, described in 1988, involves two pyridoxal groups linked by phosphates of different lengths (89). As shown in Table 4, the yield of intramolecularly cross-linked hemoglobin increases dramatically with increasing length of the phosphate backbone. It is beheved that the site of reaction of (bis-PL) is between the amino-terminal amino group of one P-chain and the... 

Transannular Te N interactions have also been employed to stabilize compounds of the type 15.24 with terminal Te=E (E = S, Se) bonds.The Te=Se bond length in 15.24b is 2.44 A (cf. 2.54 A for a Te-S single bond) and d(Te N) = 2.62 A. Intramolecular coordination was also employed in the isolation of the first aryl-selenenium and -tellurenium cations 15.25a,b as [PEg] salts. 

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