Palladium-Catalyzed [4+2] Cross-Benzannulation Reaction of Conjugated Enynes with Diynes and Triynes

Abstract

The enyne-diyne [4+2] cross-benzannulation proceeded smoothly in the presence of Pd(0) catalyst to give 1,2,4-trisubstituted benzenes 8a-j, 1,2,3-trisubstituted benzenes 9a-i, 1,2,3,5-tetrasubstituted benzenes 11a-k, 1,2,3,4-tetrasubstituted benzenes 11l,m, and 1,2,3,4,5-pentasubstituted benzenes 11n-p in moderate to quantitative yields. In all cases the reaction was found to be regiospecific with regard to substitution at the benzene ring. The palladium-catalyzed [4+2] cycloaddition of monosubstituted conjugated enynes 3a-c and 5a with unsymmetrical diynes 13a-j and triynes 16a-g also proceeded with perfect regiochemistry with regard to substitution at the benzene ring. However, since two differently substituted triple bonds are present in the enynophiles 13 and 16, the enyne preference toward either triple bond in the enynophiles became an issue, and in most cases, two regioisomeric products were obtained. The detailed deuterium-labeling studies were performed, and the mechanism of this regiospecific [4+2] cycloaddition between enynes and diynes was proposed.

New Advances in Selected Transition Metal-Catalyzed Annulations

“…There again, the size of alkynyl substituent is rather small, thus the bulky terminal substituent governs the regiochemistry (entries 9, 10). 5 We felt that the rather statistical distribution of products in the benzannulation of diphenyltriyne (entry 11) cannot be explained by steric reasons only, and probably electronic factors could also play a role in this reaction. Studies to determine the role (if any) of electronic factors on the regiochemistry of benzannulation are in progress in our laboratories.…”

“…However, when the propargylic position is substituted by a heteroatomic group (in this case, OTBS), bicyclic 77 forms rather quickly as the single product instead of the expected pyrrole (Scheme 39). The mechanism is presumed to take place via initial propargyl-allenyl isomerization followed by two successive [1,5] …”

“…Different types of mono-, di-, and trisubstituted enynes were involved into this transformation, providing tri- (16,17), tetra- (18,19), and pentasubstituted arylalkynes (20), respectively. 5 The requirement for Z-geometry of 1-substituted enynes can be overruled if the substituent R 3 = EWG (ester or cyano group, Scheme 1). E-to Z-isomerization of these activated enynes can take place under rather drastic reaction conditions, albeit slowly, the overall benzannulation process proceeds with reasonable efficiency.…”

Pd(0)‐ and Pd(II)‐Catalyzed Reactions of Alkynes and Benzynes

“…Benzannulation of the highly reactive enyne 195, possessing an EWG, was carried out in a fluorous biphasic system of perfluorodacalin, toluene, and hexane using perfluoro-tagged triarylphosphine 197, and the disubstituted The aniline derivative 208 was obtained by cross-benzannulation of the aminoenyne 207 with dodeca-5,7-diyne (50) [64]. Cross-benzannulation of the 1,4disubstituted enyne 209 with the diyne 50 afforded the 1,2,3,4-tetrasubstituted benzene 210 [63]. Pentasubstituted benzene 212 can be synthesized by the coupling of the trisubstituted 1-buten-3-yne 211 with the diyne 50 [63].…”

Rapid and Easy Access to (E)‐1,3‐Enynes, 1,3‐Diynes and Allenes Starting from Propargylic Acetals, Exploiting the Different Reactivity of Lithium and Mixed Lithium–Potassium Organometallic Reagents

“…Conjugated enynes and diynes have been used in the past as substrates in Pd 0 -catalyzed [4π+2π] benzannulation, [1] Diels-Alder cycloaddition, [2] cross-metathesis [3] and thiocarbonylation to 2-thiocarbonyl-1,3-dienes. [4] Moreover, conjugated enyne and diyne systems are found in a number of natural products such as histrionicotoxin, [5] laurencin [6] and the neocarzinostatin chromophore.…”