Lithium Hydroxide → Ammonia

Participants

Reaction Steps

Thus, 29 is transesterified (0.5 equiv. of n-Bu2Sn═O, EtOH, or i-PrOH, 25° C., 48 h., 50% and 34%) to afford esters 30 and 31, respectively. 29 is reduced (1.2 equiv. of diisobutylaluminum hydride (Dibal-H), toluene, −78° C., 0.5 h., 52%) to provide the allyl alcohol 32. 32 is O-allylated (2.0 equiv. of NaH, 3.0 equiv. of MeI, 0° C., 1 h., 95%), or is acylated (1.2 equiv. of MeOC(O)Cl, 2.0 equiv. of Et3N, 0.1 equiv. of 4-DMAP, CH2Cl2, 25° C., 24 h., 90% or 1.2 equiv. of MeC(O)Cl, 2.0 equiv. of Et3N, 0.1 equiv. of 4-DMAP, CH2Cl2, 25° C., 24 h., 90%) to afford compounds 33, 42 and 43, respectively. 29 is hydrolyzed (4.0 equiv. of LiOH, THF:H2O (10:1), 25° C., 24 h. 88%) to the acid which is aminated by mixed anhydride formation followed by exposure to an amine, (1.2 equiv. of EtOC(O)Cl, 1.5 equiv. of Et3N, 0.1 equiv. of 4-DMAP, CH2Cl2, 25° C., 1 h., then 3.0 equiv. of NH3, MeNH2, PbNH2 or ((CH2)5)N, CH2Cl2, 25° C., 12 h., 85%-95%) to provide amides 37-40. 29 also undergoes cyclopropanation (10.0 equiv. of CH2N2, 0.2 equiv. of Pd(OAc)2, Et2O, 25° C., 12 h., 95%) to afford compound 35.

Provenance & Evidence