Formation of Isomeric 3-Azabicyclo[3.3.1]nonanes in a Reaction of 1-(2-Hydroxyethoxy)-2,4-dinitrobenzene with Sodium Borohydride, Formaldehyde, and Methylamine

Abstract

Anionic hydride adduct of 1-(2-hydroxyethoxy)-2,4-dinitrobenzene was brought into a double Mannich condensation with formaldehyde and methylamine to furnish a mixture of isomeric 3-azabicyclo[3.3.1]nonanes: 3-methyl-6-(2-hydroxyethoxy)-1,5-dinitro-3-azabicyclo[3.3.1]non-6-ene and 3-methyl-6,6-ethylenedioxy-1,7-dinitro-3-azabicyclo[3.3.1]nonane. By means of NMR spectroscopy, X-ray diffraction analysis, and quantum chemistry (PM3) we demonstrated that the spirocyclic isomer had chair-chair conformation with diequatorial orientation of substituents in positions 3 and 7.

Nucleophilic Dearomatizing (DNAr) Reactions of Aromatic C,H-Systems. A Mature Paradigm in Organic Synthesis

“…The Mannich condensation of 947 with formaldehyde and methylamine affords a mixture of the common product 948 and the spiro isomer 949 . It must be remembered that the treatment of the spiro Meisenheimer complex 642 (see Scheme ) derived from 946 with MeOSO 2 F leads solely to the product of methylation at the terminal oxygen atom 643 123 …”

“…It must be remembered that the treatment of the spiro Meisenheimer complex 642 (see Scheme 89) derived from 946 with MeOSO 2 F leads solely to the product of methylation at the terminal oxygen atom 643. 485 Clayden and co-workers, who developed the dearomatization of arylamides through anionic cyclization into an efficient methodology (see section 19) for organic synthesis, have provided an impressive example of its applicability with the first total synthesis of (-)-isodomoic acid C 950 (Scheme 123). 486 The isodomoic acid C is a member of the family of kainoid amino acids that was synthesized using a strategy similar to that employed in the preparation of (-)-kainic acid (see Schemes 117 and 119).…”