Domino reactions diterpenoids

NOVEL DOMINO REACTIONS FOR SYNTHESIS OF BIOACTIVE DITERPENOIDS AND ALKALOIDS... 

A SN reaction-based domino route to clerodane diterpenoid tanabalin (2-488) [258] has been described by Watanabe s group (Scheme 2.111) [259]. This natural product is interesting as it exhibits potent insect antifeedant activity against the pink bollworm, Pectinophora gossypiella, a severe pest of the cotton plant The domino sequence towards the substituted trans-decalin 2-487 as the key scaffold is induced by an intermolecular alkylation of the (5-ke toes ter 2-484 with the iodoalkane 2-483 followed by an intramolecular Michael addition/aldol condensation (Robin-... 

Barriault developed a new pericyclic domino process for the synthesis of the bioactive diterpenoid vinigrol (4-262), which was isolated from Vtrgaria nigra [92]. The natural product possesses antihypertensive and anti-platelet-aggregating properties. 4-262 contains a unique tricyclo [4.4.4.04a8a]tetradecane framework, which could be obtained by a combination of an oxy-Cope, a Claisen and an ene reaction... 

Coupling of CM and intramolecular substitution to domino processes leading to tetrahydrofurans is feasible as well [38]. However, a corresponding combination to give tetrahydropyrans is better carried out as a sequential process [38d]. Reaction of the terminal olefin 184 with allyl chloride catalyzed by ruthenium complex 2 led to tetrahydrofuran 185 by a completely diastereoseleclive cyclization of the intermediate CM product (Scieme 2.65) [38a,b]. Compound 185 was then successfully advanced to the immunosuppressive diterpenoid pyrone subglutinol B. 

The first total synthesis of this natural product was achieved by Chiu and Lam [139]. Key step of the synthesis is a rhodium-catalyzed domino cychza-tion/cycloaddition reaction to form the tricyclic core of the diterpenoid from hnear a-diazoketone 337. Concerning the mechanism of the reaction, it is hkely that the rhodium catalyst, when reacted with 337 at 0 °C, formed a carbenoid species which immediately cyclized to 341 (Scheme 14.53). This 1,3-dipole then underwent an intramolecular cycloaddition with the aUcene to give a mixture of two cycloadducts in 81% yield with 339 as the major product (dr= 1 3.1 338 339). The minor diastereomer 338 was probably formed via a less stable boat conformation of the tether in contrast to the chair conformation shown in 341, leading to the desired product Decreasing the temperature from 0 to —15 °C did not increase the dr but lowered the yield. It is also remarkable that the reaction afforded no more than 0.5 mol% of the rhodium(II)octanoate dimer ([Rh2(Oct)4]). Further transformation of 339 finally furnished (—)-indicol (340) in an overall yield of 10% over 21 steps. 

AMI, B3LYP/6-31G //AMl, and B3LYP/6-31G computational studies have been used to investigate the molecular mechanism of the domino cycloadditions between DMAD and naphthalino- and anthraceno-furanophanes. The transannular Diels-Alder reaction of the furanophane (143) successfully produced the desired isomer (144), a key intermediate in the total synthesis of the diterpenoid chatancin (Scheme 55). ... 

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