PALLADIUM-CATALYZED CYCLIZATION OF OMEGA-HALDALLENES - A NEW GENERAL-ROUTE TO COMMON, MEDIUM, AND LARGE RING COMPOUNDS VIA CYCLIC CARBOPALLADATION

A series of omega-haloallenes (4-32) as well as related omega-haloalke nes (41-45) were prepared through the application of known procedures. Their cyclization in the presence of a catalytic amount of Cl2Pd(PPh( 3))(2), a base, e.g., K2CO3, and other appropriate reagents was invest igated mostly under two sets of conditions (conditions I and II). The results summarized in Table 1 reveal the following: (1) The Pd-catalyz ed cyclization reaction of omega-haloallenes gives the desired five- t hrough twelve-membered and twenty-membered ring products in respectabl e yields. (2) The use of the dilute solution technique and n-Bu(4)NCl is advantageous in the synthesis of eight-membered and larger rings. ( 3) Formation of a carbon-carbon bond uniformly takes place at the cent ral carbon of an allene. (4) The corresponding reaction of omega-haloa lkenes fails to give eight- and nine-membered rings and displays an in triguing endo-exo cyclization mode vs ring size profile. (5) The eight -membered ring products were exclusively Z, and the eleven-, twelve-, and twenty-membered ring products were E. The stereochemistry of the n ine- and ten-membered rings depends on other factors as well. The puta tive allylpalladium intermediates can be trapped with external nucleop hiles, such as malonate esters, organostannanes, phenols, and amines, to give the corresponding derivatives. The results support the oxidati ve addition-carbopalladation mechanism leading to the formation of all ylpalladium intermediates. The results also indicate that the extents of the actual cyclization process itself may be considerably higher th an indicated by the yields of the dehydropalladation products and that some undesirable side reactions, such as double bond isomerization, c an be circumvented through trapping with nucleophiles.