Alkynes coupling, with heterocycles

Heterocyclic compounds Heterocyclic C=N systems, such as benzoxazole and related thia-zoles, react with complex 2b to yield the ring-expanded adducts, e. g. complexes 90 and 91, by formal C-X (X = O, S) bond cleavage and coupling with the alkyne. In the case of benzisoxazole, the alkyne is not coupled but eliminated, and ring-enlargement of the ben-zisoxazole leads to the N-bridged dimer 92 [48]. 

Hydroamination of Alkynes The discovery of palladium-catalyzed intramolecular addition of amines to acetylene coupled with the spectacular contribution of Hutchings opened the door for the synthesis of several nitrogen heterocycles. The first study in this field was performed by Utimoto et al., who researched gold catalyzed intramolecular 6-exo-dig hydroamination. Tautomerization of the initial enamines allowed them to obtain imines, which were thermodynamically more stable [111] (Scheme 8.20). 

In our attempt to extend the coupling reaction of arenes with alkenes to the coupling with alkynes, as shown in Scheme 4, it was found that the reaction of arenes with ethyl propiolate in TFA (trifluoroacetic acid) gave addition products instead of a coupling product [3]. This addition reaction has been extended to various alkynes and various arenes and also to intramolecular reactions for synthesis of heterocycles such as coumarins, quinolines, and thiocoumarins. 

On the other hand, unsaturated aldehydes and ketones were obtained using allylic alcohols as alkene components [68]. Similarly, allyl f-butyldimethylsilyl ether and N-allylamides gave silyl enol ethers [69] and enamides [70], respectively. The ruthenium-catalyzed alkene-alkyne coupling was successfully combined with the palladium-catalyzed intramolecular asymmetric allylic alkylation [71] to provide a novel one-pot heterocyclization method [72]. 

The Pd-catalyzed coupling reactions of alkenyl bromides with heterocyclic alkynes (40) under the above phase-transfer conditions have been employed to prepare a large number of heterocyclic alkyne derivatives, including some naturally occurring compounds (Scheme 28). The experiment conditions... 

Recently, Su used terminal alkynes direcdy in a cross-dehydrogenative coupling reaction (100 108) with heterocycles including... 

The Pd-complex of the highly water soluble, sterically demanding tertiary phosphine, dicyclohexyl(2-sulfo-9-(3-(4-sulfophenyl)propyl)-9Ff-fluoren-9-yl)phosphine was applied as catalyst in water/2-propanol mixtures for the Sono-gashira coupling of heterocyclic and aryl bromides and chlorides with various alkynes (Scheme 36). Practically, quantitative conversions were achieved at 90°C and with K2CO3 as base even in the case of the rather unreactive substrates such as 2-pyridylacetylene or 5-bromo-2-amino pyridine. No copper(I) salt was... 

In 2010, Stuart and Fagnou reported an oxidative Larock-type heterocycle synthesis using rhodium catalysis and applied it to the synthesis of paullone (Scheme 16.8) [17]. In the synthesis of paullone, acetanilide (41) was coupled with alkyne 42 in the presence of a rhodium catalyst and Cu(0Ac)2-H20 as an oxidant under air to form disubstituted indole 44 via intermediate 43 in 71% yield. Removal of acetyl and Boc groups, followed by treatment with DBU (l,8-diazabicyclo[5.4.0]undec-7-ene), resulted in paullone in a total of eight steps. 

Six-membered heterocycles were obtained from two different alkynes and other unsaturated organic substrates involving C=0 and C=N moieties. The Reppe-type cyclotrimerization can be also applied for preparation of pyridine derivatives when one of the alkynes is replaced by a nitrile. The pyridine formation from two alkynes and a nitrile with Co complexes was originated by Wakatsuki and Yamazaki [77]. Although this method is effective, there is a critical problem for the selective intermolecular coupling of two different alkynes with a nitrile. As shown in Eq. 67, two isomers of pyridine derivatives are formed when a metallacyclopentadiene reacts with a nitrile, due to the two possible orientations of the nitrile in its coupling with the unsymmetrically substituted metallacyclopentadienes. 

Intramolecular oxy palladation and amido palladation reactions onto alkynes provide a convenient way for preparing concise functionalized heterocyclic structures. As nucleophiles carboxylic acids, amines, and amides have been used. Also, further functionalization of the double bond might be achieved via cross-coupling with in situ-formed organopal-... 

Recently, Li et al. have reported an efficient 1,3-dipolar cycloaddition of azides with electron-deficient alkynes without any catalysts at room temperature in water.128 The reaction has been applied successfully to the coupling of an azido-DNA molecule with electron-deficient alkynes for the formation of [l,2,3]-triazole heterocycle (Eq. 4.66). 

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