Cyclization of 1,6-Enynes and 1,7-Diynes

Facile Pd-catalyzed cyclizations of 1,6-enyne 133 and diynes is a useful synthetic method for substituted cyclopentanes, and called cycloisomerization. The reactions 

A number of interesting applications of cycloisomerization to natural product syntheses have been carried out by Trost. As an example, total synthesis of picro-toxinin has been achieved based on cycloisomerization (Alder-ene reaction) of the 1,6-enyne system 141 as a key reaction. No satisfactory cyclization of 141 occurred when phosphine ligands such as P(o-Tol)3, DPPB, and triisopropyl phosphite were used. However, smooth cyclization took place to give the Alder-ene product in a quantitative yield at 50 °C when A,A -bis(benzylidene)ethylenediamine (BBEDA) was used as a ligand, and the triol 142 was obtained in 75 % yield after 

The cycloisomerization of 1,6-enynes proceeds smoothly in the presence of AcOH or HCO2H and the reaction is explained by the following mechanism (hydridopalladium acetate mechanism) [45]. Most importantly, oxidative addition of AcOH to Pd(0) generates H-Pd-OAc 143, and the cyclization of 1,6-enynes starts by insertion of the triple bond to 143 to afford the alkenylpalladium 144. Subsequent intramolecular insertion of the double bond gives the alkylpalladium 145. The termination step is (i-R elimination and either the diene 136 or 138 is formed with regeneration of H-Pd-OAc. It should be noted that the alkenylpalladium 144 is a similar species formed in a Heck reaction by oxidative addition of alkenyl halide to Pd(0). Based on this reaction, alkyne is a useful starter in domino cyclization of polyenynes. 

By way of an example, the formation of 147 from 146 in the presence of AcOH is explained by this mechanism [45]. Cycloisomerization of 1,7-enynes is more difficult than that of 1,6-enynes. Seemingly difficult cyclization of 1,7-enyne 148 

Highly enantioselective synthesis of the quinoline 155 was achieved via ene cyclization of the 1,7-enyne 154 using a cationic Pd(II) complex and (5)-BINAP in DMSO in the presence of HCO2H with very high % ee (98 % ee) and in high 

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