Spontaneous and diastereoselective aldol reactions of cyclic β-amino ketones in the presence of water

Determination of the relative configuration of tropinone and granatanone aldols by using TBDMS ethers

“…The crystal structure is also characterized by internal hydrogen bonding between the nitrogen N1 and the oxygen O2 atom (N1–H2O–O2). The configuration of a related granatanone aldol ( p -NO 2 -PhCHO derived [20]) was also confirmed by X-ray analysis as exo , syn with analogous hydrogen bonding [17]. …”

“…On the basis of the observed exo – endo isomerization, and trends in NMR data changes upon isomerization, we were fairly certain of the assigned stereochemistry of the new isomer as exo , syn - 3 . This procedure developed on tropinone aldols was reproduced on corresponding granatanone aldols, providing TBDMS ethers of all four possible diastereomers of 6 (Scheme 3) and identifying the major product of the solventless reaction of granatanone with benzaldehyde [20–21] as exo , syn - 4 .…”

“…The endo isomers could be prepared by equilibration combined with separation on a silica column. The major products of the direct solventless aldol reaction of tropinone and granatanone [20] were assigned the exo , syn configuration on the bases of their NMR data and NMR data of the corresponding TBDMS ethers. The assigned exo , syn configuration of the tropinone aldol was also confirmed by single-crystal diffraction.…”

“…Until recently other isomers and synthetic procedures for their preparation remained unknown. We succeeded in preparing other isomers through an unexpected direct reaction of the ketones with aromatic aldehydes in the presence of catalytic amounts of water (Scheme 1) [18–20]. In our preliminary synthetic report the major isomeric products accessible under these conditions were assigned the exo , syn configuration.…”

“…In our preliminary synthetic report the major isomeric products accessible under these conditions were assigned the exo , syn configuration. DFT calculations suggest that selectivity in the solventless reaction results from equilibration and the higher stability of the O–H … N-hydrogen-bond-stabilized conformer of the exo , syn isomer [20–21]. …”