Cyclization with Alkynes

Ackermann and coworkers explored the same cyclization reactions, which were conducted with catalytic amount of KPFg and Cu(OAc)2 H2O in f-AmOH at 120 C for 16h (Eq. (7.6)) [11]. They also proposed a similar catalytic cycle involving acetate-assisted rate-determining C-H bond metalation step according to mechanistic study. 

Hydroxyl group-directed oxidative annulations with alkynes for the production of fluorescent pyrans were reported (Eq. (7.7)) [12]. Not only naphthols but also 4-hydroxycoumarin and 4-hydroxy-substituted quinolin-2-one underwent this ruthenium(II)-catalyzed C-H/O-H bond functionalization process in a highly chemo- and regioselective manner. Competition reactions showed that electron-deficient alkynes are more reactive. Deuterium experiments also revealed a reversible C-H bond ruthenation step via carboxylate assistance. 

N-phenoxypivalamide substrates bearing electron-withdrawing groups. Competition experiments revealed that the electron-deficient diarylalkynes were more reactive. 

Recently, Ackermann and coworkers reported aliphatic hydroxyl-directed oxidative annulation reactions of benzyl alcohols with alkynes to form isochromene derivatives (Eq. (7.11)) [16]. This C-H/O-H functionalization process performed smoothly by using [RuCl2(/ -cymene)]2 (5 mol%)/AgPFg (20 mol%) as catalyst and Cu(OAc)2 H2O (20 mol%) as oxidant under an atmosphere of air. Various tertiary benzylic alcohols, a,a-dimethylallyl alcohol, and diverse internal alkynes are appropriate substrates for this transformation. The reaction occurred with moderate to high regioselectivity for unsymmetrical alkylarylacetylene, and an irreversible C-H metalation step is involved in the catalytic cycle. 

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The cyclobutenone 70 is transformed to the r/4-vinylketene complex 72 with (t/5-indenyl)Co(PPh3)2 71. The vinylketene complex 72 undergoes cyclization with alkynes to produce the corresponding phenols 73. FeCl3 oxidation of the (2-phenylvinyl)ketene complex, however, leads to the naphthol 74. A catalytic synthesis of phenols via the vinylketene intermediates 72 is achieved by the use of Ni(COD)2 as a catalyst [36]. (Scheme 26)... 

Scheme 56 Mo-promoted cyclization of cyclooctatetraene and its co-cyclization with alkynes. 

The extended conjugation in compounds which have a iV-side-chain containing —CH—C=N enables it to undergo a I,S-addition cyclization with alkynes. 

Most of the useful iodine transfer radical reactions arise from the addition of alkyl iodides, which have been activated by one or more adjacent carbonyl or nitrile substituents, to unactivated olefins. This both labilizes the initial iodide, facilitating chain initiation, and helps ensure that the atom transfer step is exothermic. The requisite iodides are typically synthesized by deprotonation with EDA or NaH, followed by iodination with I2 or A-iodosuccinimide. Cyclization of an iodoester yields primarily lactone product, proceeding through the intermediacy of the I-transfer products as shown in Scheme 5 [19]. Reactions in which a-iodoesters cyclized with alkynes also proved efficient. Similar ketones yielded less synthetically useful mixtures of cyclopentyl and cyclohexyl (arising from 6-endo transition states) products. 

Ortho C-H Bond Activation Regioselective Oxidative Cycloaddition of Aromatic Amides to Alkynes. Cyclometalation reactions with nickel phosphine COD complexes used an amido nitrogen atom as the coordinating atom. The insertion and cyclization with alkynes is then proposed to proceed via the cyclometalation nickel intermediate as an active center to give the six-membered isoquinolone derivatives shown in Eq. (6.6). In 2013, Chatani et al. [22] also reported on these chelation-assisted transformations in details as the review articles. 

Diyne 47 bearing two sterically demanding boryl pinacolates at both ends could not be co-cyclized with alkynes when using CpCo(C2H4)2. The desired products 48 to 51 could, nonetheless, be obtained in moderate yields when using HI as a catalyst (Scheme 1.13) and cross-coupled with various aryl halides to give 52 to 55. 

An N-acyliminium ion was utilized as the electrophile in a key step of Hiemstra s enantioselective synthesis of the unnatural enantiomer of gelse-dine (148, Scheme 11.24) [123]. In this synthetic endeavor it was discovered that treatment with iodide promotes the participation of the allene as the nucleophile to give the cyclized vinyl iodide 147 in 42 % yield. This finding is related to Overman s previous investigations of halide-promoted iminium ion cyclizations with alkynes as the nucleophilic cyclization terminators (cf. 149 150) [124]. The allene cyclization step (145 146—>147) afforded a rapid route to the skeleton of gelsedine (148), thus enabling the total synthesis of this natural product [123]. 

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],... 

TABLE III. Alkynylpyrazoles Prepared by Cyclization of Alkynes with Diazo Compounds [68CB3700 68LA113 88JOM247 91ZOB2286]. 

Alkenyl radicals generated by addition of trialkylstannyl radicals to terminal alkynes can undergo cyclization with a nearby double bond. 

The above-mentioned important and impressive applications of titanocene mediated and catalyzed epoxide opening have been achieved by using the already classical 5-exo, 6-exo and 6-endo cyclizations with alkenes or alkynes as radical acceptors. Besides these achievements, the high chemoselectiv-ity of radical generation and slow reduction of the intermediate radicals by Cp2TiCl has resulted in some remarkable novel methodology. 

Benzocyclobutenedione 57 is transformed to the phthaloylmetal complex 58 by treatment with Fe(CO)5, RhCl(PPh3)3, and CoCl(PPh3)3. The phthaloyliron complex 58 (M=Fe) reacts with alkynes, and subsequent acidification under air then gives the naphthoquinone 59. The cyclization of the phthaloyl-cobalt 58 (M=Co) with alkynes requires AgBF4-activation [32]. (Scheme 22)... 

Alder/retrograde Diels-Alder reaction sequence of a diaryl alkyne with a 3,6-dicarbomethoxy tetrazine. The resulting diazine (14) is then reduced, cleaved and cyclized with Zn/acetic acid to the 2,3,4,5-tetrasubstituted pyrrole (15), which is then N-alkylated with a-bromo-4-methoxyacetophenone to give a pentasubstituted pyrrole (16). The synthesis of lukianol A is completed by ester hydrolysis, decarboxylation, ring closure and deprotection. 

Scheme 54 Cyclization of alkynes with metal-carbyne complexes containing Cr or W.

Arylative cyclization of alkynals with arylboronic acids is catalyzed by rhodium-diene complexes and even proceeds enantioselectively in the presence of a chiral diene (Equation (48)).399... 

Recently, addition of organorhodium species to nitriles has been reported.420 4203 4201 Intermolecular reaction of benzonitrile with phenylborate (accompanied with r//w-aryiation) (Equation (65)), arylative cyclization of acetylenic nitriles (Equation (66)), and cyclization of 2-cyanophenylboronic acid with alkynes or strained alkenes (Equation (67)) are proposed to proceed via this process. 

Ni(COD)2 alone catalyzes intramolecular alkylative cyclization of an alkynal with diethylzinc, while Ni(COD)2/PBu3 catalyzes reductive cyclization with the same zinc reagent (Scheme 87). 

Enantioselective catalysts have been developed for cyclization of dienyl aldehydes and coupling of aldehydes with alkynes (Equations (74) and (75)). For reactions with dienes see Refs 433 and 433a, and for reactions with alkynes see Refs 433b I33e. Chiral monodentate phosphines have proved to be effective. 

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