Sequential hydroarylation

Aryl and 4-vinyl derivatives of 2,2-dialkylchromenes have been obtained from the Pd-catalysed reaction of tertiary 3-(2-bromophenyl)propynols 9 with aryl iodides and vinyl triflates, respectively. The sequential hydroarylation/hydrovinylation and cyclisation steps can be carried out in a one-pot process <06SL909>. 

C.i.a. Sequential Hydroarylation (Hydroalkenylation)/Cyclization. Since the cis stereochemistry of addition pushes the substituents of the acetylenic moiety to the same side of the olefinic double bond, a cyclization reaction can follow the addition step when these substituents bear suitable nucleophilic and electrophilic centers, and the whole process resembles a valuable straightforward methodology for the preparation of cyclic compounds (Scheme 20). Cyclization can occur under hydroarylation(hydroalkenylation) conditions—either before or after the substitution of the carbon-hydrogen bond for the carbon-palladium bond—or by subjecting the isolated hydroarylation(hydroalkenylation) product to suitable reaction conditions. This strategy has been employed successfully to develop new routes to various heterocycles. 

A Pd-catalyzed reaaion of an arylboronic acid with aliphatic nitriles led to 2-arylbenzo[lr]furans (13S2241). A Pd-catalyzed addition of potassium aryltri-fluoroborates to ahphatic nitriles produced 2-arylbenzo[lr]furans (13JOC5273). A tandem chemoselective synthesis of 2-arylbenzo[lr]furans was accomplished from o-hydroxy- em-(dibromovinyl)benzenes and BiArj re nts under palladium-catalyzed conditions (12EJOC781). 2,3-Diarylnaphthofurans were generated using sequential hydroarylation of naphthols and alkynes in the presence of In(OTf)3 under microwave irradiation (13OL2190). 

As an extension of the Heck reaction, Pd-catalyzed hydroarylation of alkynes and alkenes continnes to attract high level of research interest in simple couphng processes and in cyclization reactions. The use of this type of transformation as part of a domino reaction will be of increasing interest. The research in the field of domino reactions is attracting considerable attention in synthetic organic chemistry since it enables the rapid assembly of complex molecirles in one-pot processes. Very elegant examples of palladium-catalyzed cascade processes where a single catalytic cycle entails several sequential bond transformations have been recently reported [la, b, 2a, b, c]. 

Arylchrom-3-en-2-ols and 3-arylcoumarins are accessible from 3,3-diethoxyprop-l-yne through sequential Pd-catalysed coupling with aryl halides and hydroarylation and finally cyclisation <97SL1367>. A facile cyclisation of o-(3-hydroxy-3-methylbutynyl)phenols effected by BBr3 leads to 4-bromo-2,2-dimethylchromenes the bromine can be removed by electrolytic reduction <97H(45)1131>. 

The sequential intramolecular hydroarylation of alkynes is applied to the synthesis of structurally complex extended x-systems. The gold-catalyzed sequential intramolecular hydroarylation of triynes followed by aromatization with DDQ proceeded to give triaryl-substituted diacenaphtho[l,2-y l, 2 -l] fluoranthenes, which can be used for organic light-emitting devices (Scheme 21.49) [55]. 

The sequential intramolecular hydroarylation of alkynes has been applied to the catalytic helicene synthesis. The platinum-catalyzed sequential intramolecular hydroarylation of diynes proceeded to give substituted [6]hehcenes (Scheme 21.50) [56]. 

Very recently, the enantio- and diastereoselective synthesis of an S-shaped double azahelicene has been achieved via the gold-catalyzed sequential intramolecular alkyne hydroarylation (Scheme 21.51) [57]. 

A sequential cross-methathesis/hydroarylation process was used in the enantios-elective synthesis of tetrahydrocarbazoles. The A-Boc w-indolyl alkene and croton-aldehyde were refluxed in CH2CI2 with the rethenium catalyst for 12 h, and then intramolecular hydroarylation of the resulting CM product was conducted in the presence of a chiral imidazolidinone and trifluoroacetic acid (TFA). The reaction afforded the corresponding product in 65% yield with 91% ee (Scheme 18.24) [22],... 

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