Amides anti-Bredt

Chromium aminocarbenes [39] are readily available from the reaction of K2Cr(CO)5 with iminium chlorides [40] or amides and trimethylsilyl chloride [41]. Those from formamides (H on carbene carbon) readily underwent photoreaction with a variety of imines to produce /J-lactams, while those having R-groups (e.g.,Me) on the carbene carbon produced little or no /J-lactam products [13]. The dibenzylaminocarbene complex underwent reaction with high diastereoselectivity (Table 4). As previously observed, cyclic, optically active imines produced /J-lactams with high enantioselectivity, while acyclic, optically active imines induced little asymmetry. An intramolecular version produced an unusual anti-Bredt lactam rather than the expected /J-lactam (Eq. 8) [44]. 

Figure 6.103 Top Planar and twisted amide bonds. Bottom "Anti-Bredt s" amides - nitrogen atoms at the bridgehead of bicyclic compounds cannot participate in negative conjugation characteristic of amides.

The above examples illustrate the importance of resonance that involves the amide t-system. When the electronic unity of amides is disrnpted by a structnral change (i.e. rotation), amides behave in unnsnal ways. Below, we will provide several additional examples of the anti-Bredt s amides distorted by the constraints imposed by their bicyclic structnre. The nsnally robnst N = C partial double bonds of amides become very sensitive towards hydrolysis and polymerization when the nitrogen atom is placed at a bridgehead position. 

Towards anti-Bredt s amides The first hint of decreased stability comes from the fact that such twisted amides are hard to prepare. For example, the early efforts of Lukes to incorporate a nitrogen at a bridgehead position in a bicyclic ring system were unsnccessfnl (Fignre 11.54). ... 

Figure 11.54 Unsuccessful synthesis of 2-quinuclidone, an anti-Bredt amide, contrasts the facile prepiiration of its structural Isomer.

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