Pd-Catalyzed Tsuji-Trost Coupling of Arylboronic Acids and Allylic Esters

7 Pd-Catalyzed (Tsuji-Trost) Coupling of Arylboronic Acids and Allylic Esters 

Transition metal-catalyzed allylic substitution reactions with carbon nucleophiles are among the most important carbon-carbon bond formation methods in modem organic synthesis, because of their broad substrate scope under mild reaction conditions. In addition, they are applicable to enantioselective reactions, as well as exhibiting versatility towards the alkene functionality adjacent to the chiral centre for stereoselective derivatization. Tsuji-Trost allylic substitution, involving a (Ti-allyl) metal intermediate, has provided a particular advance in this regard [34, 35]. Most recently, Sawamura et al. [36, 37] have improved the regioselectivity of this reaction with unsymmetrically substituted allylic esters, and thus opened a new approach to sertraline. 

Starting from L-ascorbic acid, a chiral building block from nature, 2,3-isopro-pylidene-L-glyceraldehide 21 was obtained and subjected to an il-selective Homer-Wadsworth-Emmons-type reaction [38] with phosphonate 22 to give -alkene 23. Two-step manipulation of the diol unit in 23 afforded 24 which underwent y-allylic coupling to (R)-25 with 97% e.e. and 77% yield. In the last three steps, cyclic ketone (45)-4 was obtained, with approximately 65% yield. This can be converted to sertraline by one of the routes described above. 

Each step in the above cycle was experimentally confirmed by spectroscopic means and stoichiometric reactions of Pd-complexes that were considered relevant for the catalysis. 

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