Intermolecular with alkyne

Allylic halides react intermolecularly with alkynes in the presence of palladium(II) catalysts (Scheme The prodncts are vinylic halides, which have further been elabo-... 

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],... 

Aryl- and alkenylcarbene complexes are known to react with alkynes through a [3C+2S+1C0] cycloaddition reaction to produce benzannulated compounds. This reaction, known as the Dotz reaction , is widely reviewed in Chap. Chromium-Templated Benzannulation Reactions , p. 123 of this book. However, simple alkyl-substituted carbene complexes react with excess of an alkyne (or with diynes) to produce a different benzannulated product which incorporates in its structure two molecules of the alkyne, a carbon monoxide ligand and the carbene carbon [128]. As referred to before, this [2S+2SH-1C+1C0] cycloaddition reaction can be carried out with diyne derivatives, showing these reactions give better yields than the corresponding intermolecular version (Scheme 80). 

An intermolecular 1,3-dipolar cycloaddition of diazocarbonyl compounds with alkynes was developed by using an InCl3-catalyzed cycloaddition in water. The reaction was found to proceed by a domino 1,3-dipolar cycloaddition-hydrogen (alkyl or aryl) migration (Eq. 12.68).146 The reaction is applicable to various a-diazocarbonyl compounds and alkynes with a carbonyl group at the neighboring position, and the success of the reaction was rationalized by decreasing the HOMO-LUMO of the reaction. 

The 121/Cl3SiH combination selectively cross-couples alkenes with alkynes intermolecularly to give acyclic homoallylic silanes 127 and 128 (Eq. 22) [73]. 

The moderate level of regioselectivity seen in the alkyne insertion is dependent on added PPI13, but the alkene insertion occurs with excellent regioselectively. This is the only catalytic, late transition metal system shown to intermolecularly couple alkenes with alkynes. 

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. 

Intermolecular [4+2]-cycloaddition of vinylallenes with alkynes is efficiently mediated by means of an electronically tuned rhodium catalyst (Scheme 16.81) [91]. A five-membered rhodacycle is formed from the vinylallene. Coordination followed by insertion of an alkyne to the rhodacycle generates a seven-membered rhodacycle, from which rhodium(I) is eliminated reductively to produce a cyclohexatriene, leading to the aromatic compound. 

As an extension of intermolecular reactions described earlier, some intramolecular lEDDA reactions of electron-deficient pyridazines with alkyne dienophiles have been presented <1998MOL10, 2001TL7929>. 

Pd/tppts-catalysed intermolecular sp-sp couplings to afford diynes and sp2-sp coupling of 2-iodophenols or iodoanilines with alkynes followed by intramolecular cyclization to benzofurans and indoles, respectively, with moderate to good yields in H20/CH3CN solvent mixtures have also been described.517 8... 

Among the wide variety of unsaturated functionalities which participate in the cobalt-mediated [2+2+2] cycloaddition that has proved to be a powerful tool for the assembly of complex polycyclic molecules are a number of aromatic heterocyclic double bonds, such as those in pyrrole and indole <20000L2479, 2001JA9324 and references therein>. Indoles, including those substituted at C-3, can be cyclized, both intra- and intermolecularly, with a wide variety of alkynes to yield functionalized products in moderate to good yields. A stereoselective cobalt-mediated [2+2+2] cycloaddition reaction between the W(pent-2-en-4-ynoyl)indole moiety of tryptamine derivative 1093 (R = (CH2)2NHAc) and acetylene has been employed for the formal total synthesis of strychnine 1097, the most famous Strychnos alkaloid and a commonly used rodenticide and animal stimulant (Scheme 213). 

However, their intermolecular addition reactions with alkynes are mostly aimed at synthesizing substituted aLkenes, ° and only very few cascade reactions that are initiated by P radical addition to C = C triple bonds have been reported. Renaud and coworkers developed a simple one-pot procedure for the cyclization of terminal alkynes mediated by dialkyl phosphites (Scheme 2.35). In this radical chain procedure, dialkyl phosphite radicals, (R0)2P =0, undergo addition to the C = C triple bond in 190, which triggers a radical translocation (l,5-HAT)/5-eAO cyclization cascade. The sequence is terminated by hydrogen transfer from dialkyl phosphite to the intermediate 194 and regeneration of P-centered radicals. 

Formation of polycyclic ring systems via intermolecular reactions of Fischer carbenes with alkynes can be achieved. In a metathesis-type reaction, reactions of 1,6-enynes afford... 

Cyclopropene can also be used as the aUcene component and affords bicyclo[3.1.0]hexen-2-ones upon reaction with alkyne dicobalt octacarbonyl complexes in the presence of NMO (Scheme 250). Vinyl ethers and vinyl esters serve as ethene equivalents in Pauson-Khand reactions. For example, reaction of vinyl benzoate with complex (169) furnished cyclopentenone (170) (Scheme 251). This reaction was used in a synthesis of (-l-)-taylorine and nortaylorine. Allenes participate in intermolecular Pauson-Khand reactions affording alkylidene-substituted cyclopentenones (Scheme 252). ... 

Later, Arcadi showed that /J-keto-imines react with alkynes intramolecularly to give pyrroles. The intermolecular animation with aniliaes was later developed by Hayashi and Tanaka using a cationic Au(I) catalyst to form imines (equation 27). More recently, Arcadi etal. developed an intramolecular version for the cyclization of o-alkynylanilines to form indoles (equation 28) and Li reported a double intra- and intermolecular hydroamination to obtain A-vinylindoles. " O-Substituted hydroxylamines can also undergo this type of transformation to dihydroisoxazole derivatives. " " Tandem sequences that involve a first alkyne-hydroamination step with anilines have been recently developed " " and are similar to the previonsly discnssed additions with phenols that access isoflavone skeletons. 

Imines react with alkynes to give pyrroles (equation 29). " A related transformation of azides has been reported by the group of Toste to afford pyrroles by an acetylenic Schmidt reaction (equation 30). " In an intermolecular-related addition, gold triazolates are obtained. The intramolecnlar hydroamination of trichloroacetimidates derived from propar-gyl and homopropargyl alcohols also proceeds with cationic An(I) as catalysts. ... 

AUyl propargyl ethers (oxygen-tethered 1,6-enynes) also react intermolecularly with alcohols or water to give six-membered ring acetals or hemiacetals (equation 52) AUyl silyl alkynes react somewhat similarly with Au(I) catalysts in the presence of alcohols to give cyclic or open alkenylsilanes (equation 59). Both types of products are the result of... 

The cocycloaddition of a,d)-cyanoalkynes with alkynes is another efficient entry to bicyclic pyridines. In this process an intermediate metallacyclopentadiene is formed intermolecularly from the cyanoalkyne and the alkyne. The larger alkyne substitutent ends up nearer the metal with very high regioselectivity except in the case of 2-hexyne, where selectivity is reduced to about 3 2 (equation 43). ... 

Scheme 11.3 Intermolecular Pauson-Khand reaction with alkyne and 2-pyridylsilylalkene.

Sulfenic acids also react with alkynes, and (r-butylsulfinyl)alkynes (85) eliminate 2-methylpropene on thermolysis to give the ( )-alkenyl sulfoxides (87) stereoselectively via cyclization of the intermediate sulfenic acids (86 Scheme 20)7 The stereochemistry of the adduct (87) is established by the mechanism of sulfenic acid addition. For the intermolecular trapping of sulfenic acids by alkynes, generation of the sulfenic acids by thermolysis of the corresponding 3-sulfinylpropionitrile (88 equation 35) is the preferred route. Sterically hindered sulfenic acids have also been generated by flash vacuum pyrolysis of sulfoxides and trapped intermolecularly by alkynes. ... 

Bis(disilanyl)dithiane 32 is a good precursor for intermolecular bis-silylation of alkynes. In the presence of the isonitrile-palladium catalyst 34, the facile intramolecular Si-Si bond metathesis produces reactive four-membered cyclic bis(organosilyl)palladium(II) intermediate 34, which then reacts with alkynes to afford five-membered cyclic products 55 in high yields (Eq. 24) [20,30]. 

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-... 

Synthesis of cycloheptenes by intermolecular 5+2 cycloaddition of singlcyclopropaves with alkyner catalyzed by Rh(CO)2CI2. 

Intermolecular coupling of ketyls with alkynes has proven successful in some instances [63]. Using this protocol, allylic alcohols are typically generated in good yields, but often as a mixture of E/Z isomers (Eq. 54). Additionally, some type of activation of the triple bond is necessary. In particular alkynyloxiranes have proven to be very useful substrates for the generation of to 2,3-pentadiene-l,5-diols (Eq. 55)... 

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