The Mori synthesis ((-) chiral, 2003) was the first one containing an asymmetric reaction step. It also features a large number of Pd catalyzed reactions. In it N-tosyl amine 1 reacted with allyl carbonate 2 in an allylic asymmetric substitution using Pd(dba) and asymmetric ligand (S-BINAPO) to chiral secondary amine 3. Desilylation of the TBDMS group next took place by HCl to the hydroxide and then to the nitrile 4 (NaCN) through the bromide (PBr). Heck reaction (Pd(OAc) / MePPh) and debromination (AgCO) afforded tricycle 5. LiALH Nitrile reduction to the amine and its BocO protection to boc amine 6 was then followed by a second allylic oxidation (Pd(OAc) / AcOH / benzoquinone / MnO) to tetracycle 7. Hydroboration-oxidation (9-BBN / HO) gave alcohol 8 and subsequent Swern oxidation ketone 9. Reaction with LDA / PhNTf gave enol triflate 10 and the triflate group was removed in alkene 11 by reaction with Pd(OAc) and PPh.
Detosylation of 11 (sodium naphthalenide) and amidation with acid chloride 3-bromoacryloyl chloride gave amide 12 and another Heck reaction gave pentacycle 13. double bond isomerization (sodium / iPrOH), Boc group deprotection (triflic acid) and amine alkylation with (Z)-BrCHCICH=CHOTBDMS (see Rawal) gave compound 14 (identical to one of the Vollhardt intermediates). A final heck reaction (15) and TBDMS deprotection formed (−)-isostrychnine 16.