Method of preparing phosphodiesterase IV inhibitors

A process for the preparation of a compound of structural formula I:

• ##STR13## comprises treating an intermediate 2:
• ##STR14## wherein R1 is as described below, an organometallic reagent belonging to the group consisting of a Grignard reagent (R.sup.2 MgX), organozincate reagent, a mixture of NaBH4 and R.sup.2 HgCl, wherein R.sup.2 is described below and X is Cl, Br, I, Li, MgBr, Li(Cl) or MgCl;
• and a nickel catalyst belonging to the group consisting of Cl.sub.2 Ni, Cl.sub.2 Ni(PPh.sub.3).sub.2, Ni(CO.sub.2 R.sup.2).sub.2, Ni(stearate).sub.2, Ni(cyclohexanebutyrate).sub.2 and Ni(acac).sub.2 ;
• in a solvent belonging to the group consisting of toluene, THF, diethyl ether, glyme, or diglyme;
• mixing the resultant solution at a temperature of about 0.degree. C. to about 65.degree. C. to produce Compound I and isolating compound I,
• wherein:
• R1 and R2 independently are aryl, C.sub.2-15 alkenyl or C.sub.1-15 alkyl, either unsubstituted or substituted with one or three substituents, which can be the same or different, selected from the group consisting of Ra;
• R.sup.a belongs to a group consisting of C.sub.1-6 alkyl, aryl, halo, --N(R.sup.3).sub.2, --NO.sub.2, --CN, --OR.sup.3, --C.sub.3-6 cycloalkoxy, --CO(R.sup.3), --COOR.sup.3, SO.sub.2 R.sup.3 and --SR.sup.3 ;
• and
• R3 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl and aryl, said alkyl, alkenyl or aryl optionally substituted with 1 to 3 groups of R.sup.a.