Steroids Mitsunobu reaction

Entry 10 illustrates the application of the Mitsunobu reaction to synthesis of a steroidal iodide and demonstrates that inversion occurs. Entry 11 shows the use of the isolated Ph3P-Br2 complex. The reaction in Entry 12 involves the preparation of a primary iodide using the Ph3P-I2-imidazole reagent combination. 

Several examples of reactions of allyl alcohols under Mitsunobu reaction conditions using diethyl azodicarboxylate (DEAD) and triphenyl phosphine giving allyl amines are known. An example is the reaction of the steroid 5 with azide nucleophiles under Mitsunobu reaction conditions, giving the corresponding azide 6 in 63 % yield (Eq. (3)) [5]. The reaction is regioselective with inversion of the configuration and no SN2/ substitution is observed. 

Since the use of activated amines in the Mitsunobu reaction is very extensive, additional examples are listed in the figure below. Mitsunobu reactions that incorporate protected guanyl units work very well. Proline derivative 151 was prepared from a doubly protected guanyline equivalent in 80% yield. Benzimidazoles can be readily alkylated with a number of different alcohols. In the context of non-steroidal progesterone receptor... 

Intermediate 331 was used in the reaction with ketone-derived sugars 133 (from D-glucose) or 270 (from D-fructose) and with the protected estrone 280 so that, after hydrolysis, diols 337-339"° " were obtained in 25-80% yield. Further cyclization of these diols under Mitsunobu-type reaction conditions (PPh3, DIAD, benzene reflux) gave the mixed heterocyclic sugars 340 and 341"°, and the steroid derivative 342", respectively, in 45-50% yield. 

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