Synthesis platencin

Several groups exploited the power of the intermolecular Diels-Alder reaction early in their syntheses for the formation of substituted cyclohexenes. In his synthesis of platencin, Nicolaou used a Danishefsky-like diene in an asymmetric Diels-Alder reaction for the synthesis of a chiral cylohexenone. Kanai and Shibasaki developed a catalytic asymmetric Diels-Alder reaction promoted by barium isopropoxide for the first step in their synthesis of Tamiflu. Danishefsky constructed the cyclohexene ring in paecilomycine A by employing a highly e t/o-selective Diels-Alder reaction of siloxydiene 115 and enyne dienophile 116 to yield target 117. ... 

Intermolecular Diels-Alder reactions are also highly useful for the construction of polycyclic carbocycles in natural product total syntheses. Rawal combined a cyclohexadienone with a Danishefsky-type diene to yield a c -decalin in his total synthesis of platencin. °° Stratakis also generated a cw-decalin upon combination of a quinone dienophile and an acyclic diene during the production of acremine G. Nakamura and Hashimoto employed an intermolecular Diels-Alder reaction for the construction of the G ring in pitmatoxin A. Danishefsky reacted a vinylindene diene with a quinoneketal dienophile to form the tetracyclic framework of fluostatin... 

During our recent study on utilizing tropone as diene for platencin synthesis [52], many other types of Lewis acid catalysts including the above mentioned oxazaborolidine catalysts all failed to promote the desired inverse-electron-demand Diels-Alder reaction. Fortunately, the dinucleus BINOL-aluminum catalysts were found to give very nice yields and enantioselectivities (Fig. 11) [53]. Activation mode in this reaction can be either intramolecular LLA assembly or double aluminum coordination to carbonyl substrate. Future research efforts are directed toward more applications with this type of catalyst, and more detailed understanding of the nature of this type of catalysts. 

New approaches to the intramolecular Diels-Alder reaction continue to be introduced. Mathias Christmann, now at the TU Dortmund, showed (Angew. Chem. Int. Ed. 2008, 47, 1450) that a secondary amine organocatalyst converted the prochiral dialdehyde 19 into the hicycHc diene 20 with high de and ee. Martin G. Banwell of the Australian National University prepared Organic Lett. 2008,10,4465) the triene 21 in high ee by microbiological oxidation of iodobenzene. On warming, 21 was converted smoothly into 22, which was carried on in a formal synthesis of platencin. 

The influence of solvents [64] and comparisons with catalysts of the diarylpro-linol series [65] were reported. For theoretical calculations on stereocontrol see Reference [66]. In addition, imidazolidin-4-one catalyzed cycloadditions have been used in several total syntheses of natural products. Intramolecular Diels-Alder reactions (IMDA) were reported as key steps in the synthesis of bicyclo-undecenes [67], amaminols [68], solanapyrones [69], telomerase inhibitor UCS1025A [70], englerin A [71], (-)-nor-platencin [72], and muironolide A [73]. In addition, asymmetric [3-1-2]-cycloadditions of azomethines were accomphshed in the presence of chiral imidazoUdinones [74]. Intermolecular cycloadditions of dihydropyridine 53 and acrolein catalyzed by imidazolidin-4-ones were reported. The chiral azabicyclo-octenol 54 was isolated as the important key intermediate in the total synthesis of lycopodium alkaloids [75] (e.g., ludduline) and oseltamivir (Scheme 4.19) [76]. 

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