tert-Amino Effect in peri-Substituted Naphthalenes: Syntheses of Naphthazepine and Naphthazonine Ring Systems

Abstract

Novel straightforward syntheses of naphtho-fused azepines and benzazonine via tert-amino effect are described. Starting from 1-naphthylamine, 8-N,N-dialkylaminonaphthalene-1-carbaldehydes could be obtained in two steps. The aldehyde was prepared by a Suzuki reaction of 8-bromonaphthalene-1-carbaldehyde with ortho-pyrrolidinophenylboronic acid. Treatment of aldehydes with active methylene compounds afforded naphthazepines and novel benzazonine ring system, respectively, through rearrangement of isolable vinyl intermediates or benzo[de]quinolinium derivatives or without isolation of any intermediates. A mechanistic investigation supports an intramolecular hydride transfer for the ring closure to azepine or azonine. Our results indicate that the tertamino effect may provide a valuable approach to the synthesis of ortho-and peri-fused aza-ring systems.The term 'tert-amino effect' was introduced by MethCohn and Suschitzky nearly forty years ago, to describe thermal rearrangement reactions of ortho-substituted tertanilines via cyclization to benzofused aza-ring systems. 1 Seven types of the tert-amino effect have been distinguished so far, according to the size of the ring formed and its mode of formation. 2 One version of type 2 reactions, the isomerization reaction of tert-anilines with an orthovinyl group and their heterocyclic analogues has received much attention, due to its high synthetic value to obtain biologically useful tetrahydroquinolines and related fused ring systems with predictable regio-and stereochemistry. 3a-3f This type of tert-amino effect can occur in two steps: the rate-limiting first step involves a hydrogen migration from the N-methylene carbon to the a-vinyl carbon affording a 1,5-dipolar intermediate that cyclizes in the second step to a tetrahydropyrido-fused system with the formation of a new carbon-carbon s-bond (Figure 1). An additional feature of such reactions is the requirement of strongly electron-withdrawing substituents in the vinyl group to stabilize the negative end of the dipolar intermediate. In context of the hydrogen migration, a sigmatropic [1,5]-hydrogen shift and an ionic mechanism with hydride transfer have been proposed.In our studies, kinetics, thermodynamics, steric features, the synthetic scope, and methodological limitations of this type of tert-amino effect have been investigated and various types of pyrido-fused diazines have been prepared. 4a-f An impressive number and diversity of very recent examples, 5a-e illustrate further the synthetic potential of type 2 tert-amino effect. Interestingly, only very few isomerization reactions have been reported, which led to the formation of a sevenmembered or larger ring. 6 In our approaches, vinyl-substituted bi-or triaryl-tert-amines A and B could be cyclized to diarene-fused azocines 7a and triarene-fused azecines, 7b respectively, via type 2 tert-amino effect (Figure 2). Following this line, we also decided to study ortho-fused aromatic ring systems, the prototype of which is naphthalene, possessing key functionalities in...

C(sp3)–H cyclizations of 2-(2-vinyl)phenoxy-tert-anilines

“…Cyclizations of fused bicyclic ( 3 → 4 ) and biaryl systems ( 5 → 6 , 7 → 8 ) with the interacting dialkylamino and vinyl groups in ortho , ortho ′ or ortho and peri positions furnished the respective 7–9 membered rings, besides the formation of novel zwitterionic phenantridium or benzo[ d , e ]quinolinium systems through a Michael type addition in several cases. 39,40 Starting from triaryl derivatives, 10-membered azecine rings could be attained ( 12 → 13 ). 41 As examples of nondirectly connected biaryl systems, where a sigmatropic hydrogen transfer could a priori be excluded, the cyclization of biphenyl derivatives bridged with a methylamino- N -methyl group ( 9 → 10 ) or an oxygen between the phenyl rings ( 14 → 15 ) were studied.…”

Incipient Nucleophilic Attack on a Carbonyl Group Adjacent to a Stereogenic Centre in Peri Naphthalene Derivatives

“…Peri ‐naphthalenes have been used widely since in investigations of interactions and bond formation. Examples include a NMe 2 or OMe group with an aldehyde, alkene, alkyne or nitrile, [5–8] hydrogen bonding to an amide nitrogen atom [9,10] or to a π‐surface, [11] novel Si−H⋅⋅⋅B bonds, [12] construction of abnormally long bonds, [13] methods for determining the degree of bonding between peri‐ groups, [14] and the promotion of reactions between groups held close together [15] . Peri‐ naphthalenes also occur in some proton sponges, [16] and systems with frustrated lone pairs, [17] while peri ‐acenaphthenes have been used to investigate interactions between the heavier main group elements [18,19] .…”

Silyl-Group Boosted Internal Redox Reaction: Hydride Shift from an Aliphatic Secondary Position for the Formation of Six- and Seven-Membered Carbocycles

“…Of interest was the fact that the present system was applicable to the formation of a seven-membered ring via the [1,6]-hydride shift, which was a rare process even for reactive nitrogen-containing substrates (Figure ). As in the case of tetralin formation reaction, the use of substrate 4b having a TIPS group was crucial to synthesize targeted seven-membered ring adduct 5 . Although the desired [1,6]-hydride shift occurred when substrate 4a having a TMS group was used, only homoallyl-type adduct 6 (38%) was formed possibly because of the difficulty of the seven-membered ring formation (slow formation of ring system) and the lability of the TMS group (easy cleavage of the C–Si bond).…”