Unraveling the C₂-Symmetric Azatetraquinane System. Simple, Enantioselective Syntheses

Abstract

Concise stereocontrolled synthetic routes to the C2-symmetric azatetraquinane 1 (or, also, the enantiomer) are described. The successful execution of the synthesis involved innovation in the methodology for [3+2] cycloaddition and stereochemical control.

Contrasting Diastereoselectivity between Cyclic Nitrones and Azomethine Ylides. Stereocontrolled Pathways to cis-anti-anti-cis-Oxazatetraquinanes from a Bicyclic Nitrone

“…In connection with this investigation, we also studied [3 + 2] cycloadditions of nitrone 7 (which is an oxygen analogue of 6 ) with very interesting results. Nitrone 7 was readily made by oxidation of bicyclic amine 8 with urea hydrogen peroxide solution at room temperature in methanol and catalytic sodium tungstate, as described previously . The reaction of nitrone 7 with 1-nitrocyclopentene in THF at 23 °C (rt) for 18 h proceeded smoothly to give a major 1:1 adduct that was readily isolated as a crystalline solid (75%).…”

“…W e recently discovered a concise enantiocontrolled synthetic route to the C 2 -symmetric azatetraquinane 1 that utilized the exo-selective [3 + 2] cycloaddition of an azomethine ylide to a cyclopentene as a key step, as shown in Scheme 1. 1 The azamethine [3 + 2] cycloaddition proceeded well with either 1-cyano-or 1-nitrocyclopentene. The X group exo selectivity with 2 (X = CN) was determined to be 90:10 and that with 3 (X = NO 2 ) was 85:15.…”

“…60% overall yield (Scheme 6). 1 Tricyclic ketone 18 served admirably as a key intermediate in a stereocontrolled synthesis of C 2 -symmetric azatetraquinane 1, as described previously. 1 The preferential formation of morpholine-exo product 16 from nitrone 7 is likely a consequence of the steric bulk of the morpholino group in 15 (see Figure 3).…”

“…Nitrone 7 was readily made by oxidation of bicyclic amine 8 with urea hydrogen peroxide solution at room temperature in methanol and catalytic sodium tungstate, as described previously . The reaction of nitrone 7 with 1-nitrocyclopentene in THF at 23 °C (rt) for 18 h proceeded smoothly to give a major 1:1 adduct that was readily isolated as a crystalline solid (75%). The structure of this compound was shown by X-ray crystallographic analysis to be that corresponding to NO 2 - endo [3 + 2] adduct 9 .…”

Nitrosyl Triflate and Nitrous Anhydride, Same Mode of Generation, but Very Different Reaction Pathways. Direct Synthesis of 1,2-Oxazetes, Nitroso or Bisoxazo Compounds from Olefins

“…We recently reported that triflyl nitrate, TfONO 2 , generated in situ from tetra- n -butylammonium nitrate and triflic anhydride in CH 2 Cl 2 solution, is a convenient and effective reagent for the synthesis of nitroolefins and for selective ortho nitration of certain aromatic substrates . This reagent was especially useful in our recently described synthesis of the C 2 -symmetric azatetraquinane 1 from cyclopentene . It is also well suited for the preparation of more complex nitroolefins, e.g., nitro-cedrene 2 (Figure ).…”