Synthesis of Highly Hindered Cyclic Amines

A recommended procedure for the preparation of highly hindered cyclic amines is illustrated by the following specific example. Reaction of Nl-isopropyl-2,2-dimethyl- 1,2-ethanediamine (1 eq.), acetone (2 eq.) and chloroform (1.2 eq.) under standard PTC conditions (CH2CI2, 50% NaOH, 2-5% BTAC, 5°C) gives a quantitative yield of a mixture of 1-isopropyl-3,3,5,5-tetramethyl-2-piperazinone and 4-isopropyl-3,3,6,6-tetramethyl-2-piperazinone in the ratio 73 27. More detailed examination of the reaction showed that careful control of the amount of chloroform used was essential, otherwise secondary reactions occurred. The type of secondary reaction which can occur is illustrated by the quantitative transformation of 2,2,6,6-tetramethyl-4- 

When 5-methoxybenzocyclobutene-l-carboxylic acid 1 is heated at 150-160°C for 45 minutes the product (48%) is 6-methoxyisochroman-3-one 2. 

Hydrolysis of l,5-diethoxycarbonyl-3-methyl-3-azabicyclo[3.3.1]non-9-one with hot 20% aqueous hydrochloric acid proceeds smoothly and gives 3-methyl-3-azabicyclo[3.3.1]non-9-one in 70% yield. 

Give a mechanism for this transformation which does not involve anti-Bredt intermediates. 

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