Tröger’s Base Twisted Amides: Endo Functionalization and Synthesis of an Inverted Crown Ether

Abstract

Taking advantage of the unconventional reactivity of twisted mono- and bis-amides of Tröger's base (TB), rac-6 and rac-7, respectively, the first synthesis of a 6-endo-monosubstituted TB analogue, rac-9, and the first rational synthesis of a 6,12-endo,endo-disubstituted TB analogue, rac-11, have been achieved. The bis-TB crown ether, meso-13, was prepared starting from rac-7. Meso-13 constitutes a rare example of a crown ether with an inverted methylene bridge-to-bridge bis-TB conformation both in solution and in the solid state, resulting in a reluctance to act as a receptor for cations.

N‐Protected 1,2‐Oxazetidines as a Source of Electrophilic Oxygen: Straightforward Access to Benzomorpholines and Related Heterocycles by Using a Reactive Tether

“…Nevertheless, this type of reactivity could be very useful in more complicated systems, such as Tröger bases, in which the benzylic positions can be lithiated in a straightforward fashion with s BuLi (Figure 2 a, 58 ). The exo ‐selective installation of an amino‐terminated chain on a Tröger base scaffold in high yield provided a very versatile handle for its further functionalization 20. In addition to carbon nucleophiles, the lithium salt of diphenylamine also reacted smoothly to afford the hydroxylamine derivative (see the Supporting Information).…”

Twisted Amides: From Obscurity to Broadly Useful Transition‐Metal‐Catalyzed Reactions by N−C Amide Bond Activation

“…[23] This methodology elegantly exploits the high electrophilicity of the carbonyl group in twisted amides,p roviding direct access to stereochemically defined Trçger's base derivativesa fter hydrogenation. [23] This methodology elegantly exploits the high electrophilicity of the carbonyl group in twisted amides,p roviding direct access to stereochemically defined Trçger's base derivativesa fter hydrogenation.…”

“…Subsequently, these authors reported the Wittig reaction using Ph 3 P=CHCO 2 Et and mono‐ and bis‐twisted amides (Scheme B) . This methodology elegantly exploits the high electrophilicity of the carbonyl group in twisted amides, providing direct access to stereochemically defined Tröger's base derivatives after hydrogenation.…”

Chemistry of Bridged Lactams and Related Heterocycles

“…397–398 Kirby demonstrated that 1-aza-2-adamantanone undergoes the Wittig reaction to give a bridged enamine under standard conditions employed for olefination of ketones (Scheme 149a), 108 Aubé utilized a Petasis olefination to afford exo-cyclic enamine with a [4.3.1] ring system (Scheme 149b), 408 while Wärnmark functionalized Tröger’s base-derived bridged lactams using the less reactive carbethoxymethylene-triphenylphosphorane under thermal conditions (Scheme 149c). 316 …”