Arylation of enelactams using TIPSOTf: reaction scope and mechanistic insight

Abstract

Triisopropylsilyltrifluoromethanesulfonate can be effectively used for the arylation of a wide range of enelactams. The multinuclear NMR study provided deep insights into the reaction mechanism.

Divergent Synthesis of Functionalized Indenopyridin-2-ones and 2-Pyridones via Benzyl Group Transfer: Two Cases of Aza-semipinacol-Type Rearrangement

“…The obtained indenopyridin-2-ones 7 seemed to be valuable compounds, capable of further derivatization as the conjugated double bond to carbonyl group in lactams has long been recognized as a reactive functional group. 20 Furthermore, since we previously investigated the Michael addition reactions to unsaturated δ-thiolactams, 21 4). As many reactions with the use of NBS and NIS leading to bromo-and iodo-substituted analogues, respectively, have been reported in the literature, 22 we decided to expand the range of accessible indenopyridin-2-one products to obtain iodo-derivatives of 6.…”

“…2 They also have been applied as valuable precursors of a variety of naturally occurring and naturally inspired bioactive polycyclic piperidines. 3 Driven by the need to synthesize novel bioactive piperidine-containing polycycles, we explored 2-pyridones as a platform for obtaining benzoquinolizidine 4 and quinolizidine 5 derivatives, aryl-substituted indeno[2,1-b]pyridones (resembling the core of haouamine 6 ), indeno[2,1-c]piperidine, 7 and benzomorphanones. 8 The latter have been achieved by treatment of easily accessible 6-benzyl-3,6dihydropyridin-2(1H)-one 9 with N-bromosuccinimide (NBS) in wet CH 3 NO 2 as a solvent and with (PhO) 3 P as a catalyst (Scheme 1).…”

“…On the other hand, it is known that an N-acyliminium ion can be generated from 6-hydroxy lactams using Lewis acid such as BF 3 •OEt 2 or TMSOTf. 19 Testing BF 3 •CH 3 COOH, TMSOTf, and additionally TIPSOTf, 4 we found that TMSOTf was the most effective, as it enabled the conversion of compound 5b into 6b in 72% yield as well as 5a into 6a in 76% yield (Scheme 2, parts II and III). Finally, due to the observed instability of some 6-hydroxylactams 5 and their efficient formation in wet nitromethane, we decided to target indenopyridines 6 in two reaction steps without isolation of the intermediate hydroxylactams, applying slightly adjusted conditions in both steps.…”