Azabicyclic systems

Theoretically, valence isomerization of 3//-azepincs can give rise to 2-azabicyclo[3.2.0]hepta-2,6-dienes 20 and/or the isomeric fused azetines, 6-azabicycIo[3.2.0]hepta-2,6-dienes 21. Practically, however, 2-alkoxy- and 2-amino-3//-azepincs 19, on photolysis, yield the 2-azabicyclic systems 20 exclusively, since such structures are stabilized by imidate or amidine resonance.238... 

Reactions of this type are mostly performed with internal nucleophiles attached to the carbon atom adjacent to the iminium nitrogen, thus leading to tropane-like azabicyclic systems. Both allyl- and propargylsilanes, activated and unactivated alkenes, and ketones have been successfully used as nucleophiles. The products 1 and 2 are also obtained via two consecutive C —C bond-forming reactions in a single operation. 

Intramolecular free radical addition has been used to prepare the 1,2-thiazepine derivatives 258 and 259 from 257 a further intramolecular radical cyclisation was then used to convert 258 to a new azabicyclic system with a bridgehead nitrogen [01JOC3564],... 

Reaction of propargyltrimethylsilane with oj-ethoxylactams under the influence of boron trifluoride affords (u-allenyllactams. The intramolecular version of this process gives rise to bridged azabicyclic systems containing the uncommon a-allenic amide functionality (equation 8). ... 

Synthesis of azabicyclic systems using nitrogen-directed radical rearrangements 070BC3071. 

Useful synthetic methodologies are based on the cyclization or rearrangement of the nitrogen-centered radicals generated in the reaction of the appropriate amides with (diacetoxyiodo)benzene in the presence of iodine [652-655]. Specific examples are illustrated by the synthesis of bicyclic spirolactams 622 from amides 621 [653] and preparation of the oxa-azabicyclic systems (e.g., 624) by the intramolecular hydrogen atom transfer reaction promoted by carbamoyl and phosphoramidyl radicals generated from the appropriately substituted carbohydrates 623 (Scheme 3.244) [654],... 

Given the success in forming novel azabicyclic systems derived from an intramolecular isomiinchnone cycloaddition/iV-acyliminium ion cyclization... 

Use of the Beckmann reaction in the quinuclidon-3 series and interaction of the bicyclic ketone (VI) with hydrazoic acid under Schmidt conditions gave rise to a new type of 1-azabicyclic system derivatives of 1,4-diazabicyclo-(3,2,2)-nonane (XLIV) [117-119]. 

An analogous expansion of the quinuclidine ring during pinacoline rearrangement of the ditertiary alcohols of the type (XLV) lead to preparation of the derivatives of another novel 1-azabicyclic system—1-azabicydo (3,2,2) - nonane (XLVI) [120, 121]. 

We investigated the incorporation of [ 1,2- C2lacetate into the tropane alkaloids independently and chose to work with Datura stramonium which produces 6)3-hydroxytropine (15). In this alkaloid the symmetry of the parent azabicyclic system is broken and all carbon atoms are represented by well separated signals in the C NMR spectrum. In the C NMR spectrum of (15) isolated from this experiment a coupling pattern was observed which indicated that in this sample as well two labeled species were present which were bond-labeled between C-2/C-3 and C-3/C-4, respectively. 

The mechanistic rationale put forth for product formation involved ketene attack on the amine moiety followed by an amino Claisen rearrangement of the zwitterionic enolate. An analogous reaction is observed with methyl propiolate and fused azabicyclic systems [14]. 

Moore and coworkers demonstrated that azabicyclic systems can also be converted to 3-pyrrolin-2-ones (e.g., 562 563), using methanol and benzoic acid with sodium benzoate (Scheme 160 1962JA3022). 

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