Alkynes, dimerization/cyclization

Scheme 87 6-Endo-dig vs. 5-exo-dig cyclization in sequential alkyne dimerization-cyclizations [156]...

Under optimized conditions, cycloisomerizations of a number of functionalized hept-l-en-6-ynes took place in good-to-excellent yields (Table 9.3). Heteroatom substitution was tolerated both within the tether and on its periphery. Alkynyl silanes and selenides underwent rearrangement to provide cyclized products in moderate yield (entries 6 and 7). One example of seven-membered ring formation was reported (entry 5). Surprisingly, though, substitution was not tolerated on the alkene moiety of the reacting enyne. The authors surmize that steric congestion retards the desired [2 + 2]-cycloaddition reaction to the point that side reactions, such as alkyne dimerization, become dominant. 

The diyne 20b, prepared by oxidative dimerization of the corresponding terminal alkyne, was cyclized to the biindole 20e using NaOEt. <95SL859> H... 

The same type of bis-functionalization has been reported for the palladium-catalyzed borylstannylative carbocy-cyclization of 1,6-, 1,5-, 1,7-diynes, bis-propargylamine, and ether.377 It should be noted that even 1,2-dialkylidene cyclobutane can be obtained in reasonable yield. Ito has proposed the related silaborative reaction involving nickel(O) catalysis.378 This reaction has been performed in an intra- and intermolecular fashion. The intramolecular reaction allows the formation of cyclic dienes and the intermolecular process proceeds through a dimerization of alkynes to give acyclic dienes. 

Cyclopentadienones.2 Cyclopentadienones are generally not useful synthons because of their ready dimerization. A new synthesis of more stable substituted cyclopentadienones involves cyclization of two substituted alkynes with carbon monoxide by the [2 + 2 + 21cycloadditions shown in equations (I) and (II). 

A similar polar cyclization of an enamine and a thioketene derivative is shown in equation (87) (76TL4283), but electron-deficient alkenes and alkynes react in a concerted fashion. Concerted cyclizations may be subdivided into those in which the sulfur atom is part of the enophile or the dienophile. Into the first category fall the dimerizations of a,( - unsaturated thioaldehydes (equation 88) which may be shown to closely follow frontier molecular orbital predictions of regioselectivity (79JOC486). Related to this are the thiochalcones (equation... 

The cyclopropanation of alkenes, alkynes, and aromatic compounds by carbenoids generated in the metal-catalyzed decomposition of diazo ketones has found widespread use as a method for carbon-carbon bond construction for many years, and intramolecular applications of these reactions have provided a useful cyclization strategy. Historically, copper metal, cuprous chloride, cupric sulfate, and other copper salts were used most commonly as catalysts for such reactions however, the superior catalytic activity of rhodium(ll) acetate dimer has recently become well-established.3 This commercially available rhodium salt exhibits high catalytic activity for the decomposition of diazo ketones even at very low catalyst substrate ratios (< 1%) and is less capricious than the old copper catalysts. We recommend the use of rhodium(ll) acetate dimer in preference to copper catalysts in all diazo ketone decomposition reactions. The present synthesis describes a typical cyclization procedure. 

Pauson and Khand discovered the very important class of alkyne/alkene/CO cyclization catalytic reactions catalyzed, once again, by Co2(CO)g see Pauson-Khand Reaction). This reaction produces a, /3-unsaturated cyclopentanones (equation 23). With unstrained alkenes the reaction works best in a stoichiometric setting, but with strained alkenes like norbomadiene the reaction can be made catalytic. These reactions have been fairly extensively studied, and the reaction proceeds through an alkyne-bridged Co2(CO)6 dimer species. Unsymmetrical alkynes lead to mixtures of the various substituted a, /3-unsaturated cyclopentanone products. 

When benzylic alcohols are the substrates, arenes behave as nucleophiles, as shown in equation (123) and for the analogs in the 1,4-addition.These reactions have been performed with alcohols that are activated by an arene substituent and another group that could be an olefin, an alkyne, or other arene (equation 140). In the case of dimerization reported by Hashmi (equation 141), primary benzylic alcohols produce dimers of the type in equation (141) that arise from the activation of this moiety, together with the expected cyclization products. In a very recently reported example, aryl-alkyl ethers are obtained by reaction with NaAuCU. ... 

Reaction with alkynes. (f-Butyldimethylsilyl)alkynes give dimers while simultaneously introducing one or two iodine atoms into the products. Certain alkynyl sulfides undergo cyclization. ... 

The intermolecular dimerization of ortho-quinodimethanes to [2.2]paracyclo-phanes is an established synthetic procedure [39]. However, with extended exo-cyclic double bond systems,para- or orf/zo-quinodimethanes yield cydophanes with alkyne groups in their bridges, such as 69, as products of an intermolecular cyclization [44]. Such para-quinodimethanes with cumulated double bonds are accessible via l,x elimination of bis-propargyl or benzyl bromides with Bu3SnSi-Me3/CsF [45]. Carbo- and heterocyclic unsaturated cydophanes have been pre-... 

Aryl and alkyl-substituted diynes and tetraynes have been synthesized in good yields (82-99%) by TBAF-promoted desily-lation and Cu-catalyzed oxidative dimerization of triisopropylsi-lyl (TlPS)-protected acetylenes (eq 38). Copper acetate was used as oxidant in this reaction. Aryl- and alkenyl alkynes were made under similar conditions (eq 39). Pd/C with TBAF was used in ligand- and copper-free, one-pot, domino Halex-Sono-gashira reactions. Similarly, TBAF promoted the synthesis of 2-substituted indoles by a tandem Sonogashira/cyclization reaction of 2-iodoanilines and terminal alkynes. ... 

The most desirable aim in benzannulation is selective cyclization of three different alkynes to give a single isomer Yamamoto offered a solution. Reaction of phenylacetylene (82) with 5-dodecadiyne (50) using Pd(PPh3)4 and additional P(o-To1)3 as a catalyst, afforded the tetrasubstituted benzene 218 as a single product in 89% yield. In this case, dimerization of phenylacetylene to 1,3-diphenylbut-l-yn-3-ene (219) took place. 

Metal-mediated cyclizations that rely on the initial complexation of an alkene or alkyne around a low oxidation state metal center are often sensitive to the presence of additional substituents (particularly electron-donating substituents), and relatively more stringent reaction conditions are often required for successful cychzation. This effect was noted in the Ni-catalyzed formal [4 -I- 4] cycloaddition reactions developed by Wender and Tebbe and is apparent when one compares the reported facility of Pd-catalyzed linear dimerization of 1,3-butadiene versus that of substituted 1,3-dienes. Similarly, the initial attempts at Pd-catalyzed cyclization of bisdiene 70a (Scheme 22) were rather disappointing. Using 0.05 equiv of [Pd(OAc)2/3 PhjP] (THF, 65 °C, 12 h), only a small... 

---