Formation of Carbocycles by Intramolecular Conjugate Displacement: Scope and Mechanistic Insights

Abstract

A detailed study has been made of a method of ring closure categorized as an all-carbon intramolecular conjugate displacement (ICD). This reaction involves intramolecular addition of a carbanion, which is stabilized by at least one electron-withdrawing group, to a Michael acceptor which has a leaving group in an allylic position. The process formally resembles a combination of Michael addition and S(N)2' displacement. The overall result is formation of a ring with loss of the allylic leaving group and shift of the original double bond to a new location spanning the positions of the electron-withdrawing substituent of the Michael acceptor subunit and the original allylic leaving group. The starting materials are easily prepared by a selenium-based version of the Morita-Baylis-Hillman reaction. The cyclizations are transition metal free and occur under mild conditions, using DBU or Cs(2)CO(3) in MeCN or THF. Acetate is a suitable leaving group and the electron-withdrawing substituent of the Michael acceptor unit can be CO(2)R, SO(2)Ph, or CN. Six- and seven-membered rings are formed efficiently, and complex structures, such as those resembling the core of CP-225,917, are easily assembled. The products of these ICD reactions are themselves classical Michael acceptors. A range of mechanisms probably operates, depending on the structure of the starting material and the reaction conditions, but conclusive evidence for a stepwise mechanism was obtained in a suitably biased case, while other observations are compatible with a concerted process or a stepwise path involving a short-lived carbanion that evades capture by a proton source.

Nitromethane with IBX/TBAF as a Nitrosating Agent: Synthesis of Nitrosamines from Secondary or Tertiary Amines under Mild Conditions

“…Spectral data: 1 H NMR δ 5.38 (s, 2H), 7.14 (ddd, J = 7.2 Hz, 1.6 Hz, 2H), 7.32–7.42 (m, 4H), 7.46 (m, 2H), 7.82 (m, 1H), 7.99 (m, 1H); 13 C NMR δ 67.6, 94.5, 128.1, 128.7, 128.8, 128.9, 131.3, 132.9, 135.2, 135.7, 141.6, 166.5. 1 H NMR and 13 C NMR match with literature report …”

Enantioselective Construction of Spirocyclic Oxindoles via Tandem Michael/Michael Reactions Catalyzed by Multifunctional Quaternary Phosphonium Salt

“…All solvents and reagents were directly used without further purification. Phase-transfer catalysts 3a , 3b – 3c , 3d , 3e , and 3h have been described, 3f , 3g , and 3i – 3l were prepared following our reported literature. , γ-Malonate-substituted α,β-unsaturated compounds were synthesized according to known procedure …”

Sequential Annulations to Interesting Novel Pyrrolo[3,2-c]carbazoles

“…The cyclization step could, in principle, generate (Scheme 7) the tetrahydroindole 14 (through a 6- endo - trig Michael addition) or the dihydroindole 15 (through an overall S N V 6- exo - trig process). A third possible way (S N V with ICD [29,30]) to 16 could be labeled again as a 6- endo - trig process. The main products ( 6 – 8 ) actually observed can find in 15 an obvious common precursor, while 14 could be the precursor not only of 6 – 8 but also of 9 , observed in our system only in a few cases ( 4g – i ).…”