Epoxides ring-opening carbonylation

Treatment of the /3-keto ester 220 with sodium ethoxide at elevated temperature triggered off an epoxide ring opening by / -elimination that was followed by the desired Knoevenagel condensation to afford the tricyclic product 206 (Scheme 34). The enone moiety in the intermediate 221 did not show a propensity for deprotonation and, therefore, the ketone carbonyl function of the enone moiety was available for a Knoevenagel condensation. The reduction of the p-keto ester (206) to the corresponding diol was the next objective. Treatment of the TES-protected -keto ester (TES-206) with DIBAH afforded the diastereomeric diols 222 and 223 in a moderate diastereoselec-tivity in favour of the undesired diastereomer 222. The diastereomers were separated and the undesired diastereomer 222 was epimerized to 223 by a sequence that consists of Mitsunobu inversion and benzoate ester reduction [98, 99]. 

Condensation of the carbonyl group with the yUde from trimethylsulfonium iodide leads initially to an addition product. The anion formed on the carbonyl oxygen then internally displaces dimethyl sulfide to give an oxirane yielding epoxide (114-3). Reaction of that intermediate with a 1,2,4-triazine leads to an epoxide ring opening with the consequent incorporation of the second heterocyclic moiety. There is thus obtained fluconazole (114-4) [125]. 

Hinshelwood (LH) process. It has been found that the ER mechanism with the epoxide ring opened via H abstraction from N2H4 is more favorable. After H transfer, the newly formed OH group can easily obtain another H from NHNH2 and desorb from the surface. Gao et al. [80] then systematically investigated the reduction of GO based on DFT calculations with cluster models. For hydrazine reduction, three possible mechanisms for epoxide reduction have been identified. However, reduction path for hydroxyl, carboxyl, and carbonyl groups has not been found. Those groups are expected to be removed by thermal reduction. 

Manipulation of the carbonyl function to epoxide 3 was accomplished by conversion to the tosylhydrazone, Shapiro olefination, and epoxidation.The latter step occurred with high ster-eocontrol, as did the epoxide ring opening with acidic methanol. Oxidation to ketone 4 was then performed, and from this product the desired derivative 5 was obtained by known procedures. 

Amines can be prepared using reactions including epoxide ring opening, addition of nitrogen nucleophiles to carbonyls followed by reduction, reduction of amides, reduction of nitriles, and nitration of arenes followed by reduction. 

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