Strychnine Heck reaction

The amines 43, 46, and 47 constituted dehydro analogs of two intermediates in Rawal s strychnine synthesis, 49 and 50 (Scheme 20).7h This suggested that a simple reduction of the C ring double-bond, while conserving a C14-C15 unsaturation, would access synthetic relay points only two (via a Heck cylization of 50) or three (via alkylation of 49 with side chain 45, then Heck reaction) steps from 1, and allow the claim of a formal synthesis. 

An elegant and efficient stereocontrolled total synthesis of strychnine has been achieved by applying intramolecular Diels Alder and Heck reations as key reactions [47]. An unusual exo-Diels-Alder reaction of 102 afforded 103, which was converted to the vinyl iodide 104. The Heck reaction of 104 using Pd(OAc)2 gave the hexacyclic strychnan system 105 smoothly in 74% yield. Hydrolysis of 105 afforded isostrychnine, which was isomerized to strychnine (106) under basic conditions. 

Scope and limitations of the Heck reaction synthesis of dienes The Heck reaction with electron-rich alkenes A synthesis of strychnine Recent developments in the Heck reaction Sp2-sp2 Cross-Coupling Reactions by Transmetallation Stille coupling... 

Rapid development in the Heck reaction has made it one of the most important of all modem methods. A dramatic example is a recent synthesis of strychnine by M. Nakanishi and M. Mori.23 This synthesis illustrates the intramolecular Heck reaction particularly well, showing examples of regioselectivity in attack on the alkene and in formation of the new alkene. The synthesis starts with a Heck reaction on enantiomerically pure 149. Attack occurs on the nearer end of the alkene to give 150 that cannot eliminate to reform the same alkene as there are no H atoms left and the alkene 151 must be formed. The stereochemistry is controlled by the short tether linking the aryl bromide and the alkene. 

Now the Heck reaction can be induced to close the ring 162. In this case the vinyl iodide forms the palladium derivative and the regioselectivity of the attack is at the 5-position of the dienone mainly because of the tether. The closure of the last ring was already known and the synthesis of strychnine 164 complete. This synthesis uses three Heck reactions and two other palladium-catalysed reactions. 

An efficient synthesis of the alkaloid strychnine makes good use of an intramolecular Heck reaction. Oxidative addition of palladium(O) into the alkenyl iodide 212 and cyclization onto the cyclohexene gave, after p-hydride elimination and silyl deprotection, isostrychnine 213 (1.214). isomerization of the new alkene to give the enone and cyclization of the alcohol onto the enone gives strychnine. 

The reaction has also been employed in a short sythesis of ( )-strychnine (Scheme Intramolecular Heck reaction of alkenyl iodide 128 yields ( )-... 

The Strychnos alkaloids possess diverse chemical structures that have attracted considerable attention in organic synthesis during the last decades. Recent studies on the synthesis of akuammicine, strychnine and leuconicine A and by Andrade et al. proved that the intramolecular Heck reaction is extremely valuable for the construction of complex polycyclic molecules. Based on Rawal s method for the construction of the D ring of Strychnos alkaloids, vinyl iodides 37, 39, and 42 undergo a regioselective and stereoselective palladium-catalyzed cychzation in the presence of Pd(OAc)2, PPha in Et3N to furnish ( )-akuammi-cine 38, and the advanced intermediates 40 and 43 in excellent chemical yields (Scheme 13.11). 

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