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A novel method for the stereospecific preparation of [4.5]spiroketal glycosides utilizing the 1,5 C−H bond insertion of alkylidenecarbenes is described. Treatment of 2-oxopropyl β-pyranosides A with lithium (trimethylsilyl)diazomethane in THF at −78 °C afforded 1,6-dioxaspiro[4,5]decenes B in good yield. Submission of the corresponding α-glycosides C to the same reagent gave the isomeric insertion products D in moderate to high yield.

The preparation of (±)-24, a model for the core of the zaragozic acids, is reported. The pivotal reaction in this endeavor is the dirhodium(II)-catalyzed intramolecular C−H bond insertion of 2-diazoacetyl-1,3-dioxane 4, a transformation which generates four of the six stereocenters present in the core structure. A novel method for the diastereoselective synthesis of pyruvic acid acetals was also developed and employed in the preparation of 4 from xylitol derivative 7.

The formal synthesis of (±)-desmethylamino FR901483 (2) is described. Construction of the unique azatricyclic skeleton of 2 was accomplished by a sequence which involved (i) preparation of dienone 7 by an N-methoxy-N-acylnitrenium ion-induced spirocyclization, (ii) formation of 2-azabicyclo[3.3.1]nonane 5 by the 6-(π-exo)-exo-trig radical cyclization of 1,7-enyne 6, and (iii) installation of the C-5 p-methoxybenzyl side chain by Lewis acid-mediated alkylation of silyl enol ether 18.

A formal synthesis of the muscarinic M1 receptor antagonist (−)-TAN1251A (7) from l-tyrosine is described. Central to this venture has been the construction of the 1-azaspiro[4.5]decane skeleton present in the natural product by an N-methoxy-N-acylnitrenium ion-induced spirocyclization. The dienone generated in this transformation, 10, was converted to (−)-TAN1251A via tricycle 9, an intermediate in Kawahara's recent synthesis of racemic 7.