Palladium-Catalyzed Highly Chemo- and Regioselective Formal [2 + 2 + 2] Sequential Cycloaddition of Alkynes:  A Renaissance of the Well Known Trimerization Reaction?

Abstract

A new concept of highly chemo- and regioselective formation of the benzene ring by a palladium-catalyzed formal [2 + 2 + 2] sequential intermolecular trimerization of alkynes is proposed. Homodimerization of terminal alkynes and subsequent [4 + 2] benzannulation with diynes gives tetrasubstituted benzenes in moderate to good yields. The introduction of two different alkynes (terminal and internal) in the first step of the sequence allows for construction of pentasubstituted benzenes from three different acyclic acetylenic units. In all cases the tetra- and pentasubstituted benzenes are formed as a single reaction product without being accompanied by any of regio- or chemoisomers. A significant acceleration of the sequential trimerization reaction in the presence of Lewis acid/phosphine combined system was observed. Mechanistic studies reveal that the Lewis acid assisted isomerization of the E-enyne formed in the first step of the sequence to the more reactive Z-isomer is responsible for the observed acceleration effect. The proposed methodology provides a conceptually new and synthetically useful route to multifunctional aromatic compounds.

[2+2+2] Cycloaddition Reactions Catalyzed by Transition Metal Complexes

“…[62] The cyclotrimerization of a diyne species with a benzyne precursor was subjected to catalysis by [NiA C H T U N G T R E N N U N G (acac 3 complex was found to be most effective, which was utilized in the total synthesis of taiwanins C and E (Scheme 38). Other examples of Pd catalysis in the synthesis of benzene derivatives include the use of PdA C H T U N G T R E N N U N G (PPh 3 ) 4 to form 1,2,3,5-tetrasubstituted benzenes, [63] the Pd 2 A C H T U N G T R E N N U N G (dba) 3 -catalyzed cycloaddition of benzyne to 1,6-diynes to afford benzo [b]fluorenones, [64] and the PdCl 2 A C H T U N G T R E N N U N G (PPh 3 ) 2 -mediated co-cyclotrimerization of benzynes with bicyclic alkenes to form anellated 9,10-dihydrophenanthrene derivatives. [65] These reports have been reviewed earlier.…”

Zirconocene‐Mediated Intermolecular Coupling of Si‐tethered Diynes with Alkynes, Ketones, Aldehydes, and Isocyanates by means of Novel Skeletal Rearrangement of Zirconacyclobutene–Silacyclobutene and Zirconacyclohexadiene–Silacyclobutene Fused‐Ring Intermediates

“…(2) in Scheme 4]. [14][15][16][17] In this work, we found that three triple bonds out of four [shown in Eq. (3) in Scheme 4] could be highly selectively integrated into a benzene derivative; one of the triple bonds in bis(alkynyl)siScheme 2.…”

Regio- and Stereoselective Homodimerization of Monosubstituted Acetylenes in the Presence of the Second Generation Grubbs Catalyst

“…Many examples of effective run of the process in the presence of transition metal complexes have been described. Catalytic activity in the process has been reported to be shown by complexes of such metals as palladium [4,[7][8][9][10][11][12][13], rhodium [14][15][16][17][18][19], ruthenium [20][21][22][23][24][25][26][27][28][29], nickel [30], iridium [31][32][33], osmium [34,35], iron [36] and the f-block metals [37][38][39]. However, a highly selective synthesis of conjugated enynes by dimerization is still a challenging process.…”