Studies towards development of asymmetric double-Mannich reactions of chiral 2-oxocyclohexanecarboxylate derivatives with bis(aminol)ethers.

A range of chiral ester and chiral imide derivatives of 2-oxocyclohexanecarboxylic acid were utilised in double-Mannich reactions with bis(aminol)ethers to develop an asymmetric synthesis of azabicyclo[3.3.1]nonanes. An improved method for the double-Mannich reaction of β-ketoesters and bis(aminol)ethers using sub-stoichiometric quantities of a Lewis acid was developed. Additionally, a sequential, double-Mannich approach was investigated incorporating chiral auxiliaries into N , O -acetals. The use of oxazolidinone auxiliaries afforded the best yields and diastereoselectivities enabling separation of the resulting diastereomers of the azabicyclo[3.3.1]nonanes. [ABSTRACT FROM AUTHOR]