Diastereoselectivity Curtius rearrangement

Fig. 14.44. A one-pot diastereoselective degradation of a carboxylic acid to a Boc-protected amine via a Curtius rearrangement Boc refers to tert-butoxylcarbonyl. The mixed anhydride B is formed by a condensation of the phosphorus ) reagent with the carboxyl group. The anhydride B acylates the concomitantly generated azide ion forming the acyl azide A. A Curtius degradation converts A to C, and the latter reacts subse-guently with tert-butanol to the Boc-protected amine.

Fig. 11.40. A one-pot diastereoselective degradation of a carboxylic acid to a Boc-protected amine via a Curtius rearrangement Boc refers to fert-butoxylcarbonyl.

The antidepressant tranylcypromine 151 was made using the Evans box ligand 133. A different bulky ester 149 gave good ee but only moderate diastereoselectivity.35 The trans diastereoisomer hydrolyses faster than the cis so the free acid was essentially pure trans. Further reactions including a Curtius rearrangement with retention gave tranylcypromine 151. 

A diastereoselective y aminoester synthesis utilized Shioiri conditions for the Curtius rearrangement of carboxylic acid 84, generated by conjugate addition to bis allyl fumarate 83 and subsequent Ireland-Claisen rearrangement. The Curtius rearrangement preserved the relative configuration at the stereogenic centers, and the product y -aminoester 85 was produced in Cbz-protected form. 

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