Heteroaryl-substituted alkynes

By using the hypersensitive molecular mechanistic probe 2-(2-methoxy-3-phenylcy-clopropyl)-5-methylhexa-2,4-diene in the 2 + 2-photocycloaddition of [60]fullerene, it was shown that the reaction proceeds via a biradical and not a dipolar intermediate.6 Zirconium-induced cyclodimerization of heteroaryl-substituted alkynes produces tetrasubstituted cyclobutenes with high regio- and stereo-selectivity.7 The ruthenium-... 

Halofuran and halothiophene derivatives undergo photochemical reactions with arylalkenes and arylalkynes and with benzo[6]furan513,514. With the arylalkenes and aryl-alkynes, heteroarylation takes place at the terminal alkene or alkyne carbon atom, while benzo[6]furan is substituted at position 2. The experimental results are interpreted in terms of solvent-separated or contact radical ion pairs. Iodothiophene and iodofuran derivatives can also be used to synthesize derivatives of benzimidazole by means of photochemical coupling515. The reaction of 5-iodothiophene-2-carboxaldehyde (157) with benzimidazole (158) giving the coupling product 159 is illustrated in equation 131. 

In recent years, transition-metal-mediated inter- or intramolecular cyclodimerization of alkynes has received lots of attention [1, 2]. During the study of the mechanism of zirconium-mediated cyclodimerization of heteroaryl-substituted alkynes [1], the zirconium intermediate 10 was successfully isolated (Scheme 1). However, in the NMR spectral data, there was no resonance in the region of 70-100 ppm, which is... 

The Dotz reaction may employ heteroaryl substituted carbenes. The fiuyl carbene 8.58 gave thebenzofuran 8.59 (Scheme 8.19). The reaction may also be intramolecular, taking advantage of the acylation of the ate complex 8.60 to introduce the alkyne (Scheme 8.20). ... 

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

SCS-MP2 and the new perturbative B2-PLYP density functional methods provide accurate reaction barriers and outperform MP2 and B3-LYP methods when applied to the 1,3-dipolar cycloaddition reactions of ethylene and acetylene.39 Phosphepine has been shown to catalyse the asymmetric 3 + 2-cycloaddition of allenes with a variety of enones (e.g. chalcones) to produce highly functionalized cyclopentenes with good enantiomeric excess.40 The AuPPh3SbF6 complex catalysed the intramolecular 3 + 2- cycloaddition of unactivated arenyne- (or enyne)-yne functionalities under ambient conditions.41 A review of the use of Rh(I)-catalysed 3 + 2-cycloadditions of diaryl-and arylalkyl-cyclopropenones and aryl-, heteroaryl-, and dialkyl-substituted alkynes to synthesise cyclopentadienones for use in the synthesis of natural products, polymers, dendrimers, and antigen-presenting scaffolds has been presented.42... 

Terminal alkynes can be coupled directly to aryl, heteroaryl, and vinyl halides or triflates in the presence of a Pd-catalyst and a base, which frequently is an amine acting both as solvent and as scavanger for the respective acid formed in the reaction. The mechanism appears to involve oxidative addition of the sp2-halide or triflate to Pd(0), followed by alkynylation of the intermediate organopalladium complex and reductive elimination of the substituted alkyne. Copper(I) iodide is a particular effective cocatalyst, allowing the reaction to proceed at room temperature (91MI2). 

The reaction of thienyllithium with organic halides to form C—C bonds has been discussed in Section 2.10.4.7.2. This cannot, however, be extended to aryl, alkenyl or heteroaryl halides in which the halogen is attached to an sp carbon. Such cross-coupling can be successfully achieved by nickel or palladium-catalyzed reaction of the unsaturated organohalide with a suitable thienyl metal derivative. The metal is usually zinc, magnesium, boron or tin occassionally lithium, mercury, copper, and silicon derivatives of thiophene have also found application in such reactions. In addition to this type, the Pd-catalyzed reaction of halogenated thiophenes with suitable alkenes and alkynes, usually referred to as the Heck reaction, is also discussed in this section. Besides these, a few other miscellaneous Pd-catalyzed substitution reactions on thiophene will also be referred to. 

Under rhodium-catalyzed conditions, hydrazine 137 undergoes oxidative annulation with alkyne 135 to furnish 1,2,3-tri-substituted indole 138 in moderate to excellent yield. The 1-aminoindole products can be substituted at C2 and C3 with aryl, heteroaryl, alkyl, and alkynyl groups (free hydroxyls and alkyl chlorides are also tolerated). 1,3-Dinitrobenzene acts as the stoichiometric oxidant and this is believed to be the first report of its use as such in a transition metal-catalyzed C-H activation (140L6176). 

A rhodium(III)/copper(II)-mediated process was reported to provide tetra-substituted enol esters in a trans-selective fashion. Overall, the reaction consists of a heteroaryl acyloxylation of alkynes. The process was initiated by a rhodium(III)-catalyzed C-2-selective activation of electron-rich het-eroarenes, such as benzo[I>]furan, and furan. Upon addition across an alkyne, a transmetalation to copper(II) enabled reductive C—O bond formation (14AGE14575). 

A gold(III)-catalyzed multicomponent coupling/cycloisomerization reaction of heteroaryl aldehydes, amines, and alkynes imder solvent-free conditions or in water has been developed as shown in Scheme 8.2 [2]. This methodology provides rapid access to substituted aminoindolizines with high atom economy and high catalytic efficiency. Especially, the coupling of enantiomerically enriched amino acid derivatives produces the corresponding A/ -indolizine-incorporated amino acid derivatives without loss of enantiomeric purity. 

Under conditions of C-H/N-H bond functionalization, aryl-, heteroaryl-, and alkenyl-substituted IH-pyrazoles underwent oxidative annulation with aryl and alkyl alkynes in high chemo- and regioselectivity in the presence of Ru(II)/AgSbFg catalyst (Eq. (7.28)) [36]. Aryl alkynes particularly bearing electron-donating substituents are more reactive in the present reaction system. A cationic ruthenium(II)-catalyzed reversible C-H bond metalation step was observed in the H/D exchange experiments. 

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