Relative Migratory Aptitude of Substituents and Stereochemistry of Dyotropic Ring Enlargements of β‐Lactones

Abstract

11 12 f a h 1 -Cx&-pCH3 -I OH 13 Scheme 4. a) I . EtMgBr, Cul, Me,S, THF; 2. H,C=CHCH,Br, hexamethylphosphoric acid triamide (HMPT) (60%); b) NaH, glyme, HCOOEt (95%); c) PhN,CI ( 8 5 % ) ; d) HCOOH (86%); e) NaOMe, MeOH, RT, 12-14d (99%); f) I . OsO,, NaIO,, MTBE, H,O; 2. MeNHOH, NaCNBH,, iPrOH, pH = 6 (85%); gj MeLi, THF, -20°C + RT (98%); hj Ac,O, pyridine, 3 h, RT (99%).carbazole derivative 1 is achieved by the addition of methyllithium to the carbonyl function, and 0-acetylization of the hydroxylamine group.['] The conversion of 13 to uleine (2) can be performed in good yields without chromatographic purification of the intermediates. The novel cascade reaction allows the application of the readily obtained trans configuration of the tetrahydrocarbazole 13 for a concise and stereoselective synthesis of uleine. This example demonstrates once more that the application of domino processes can open more efficient and shorter synthetic pathways. Experimental Section2: Tetrahydrocarhazole l(68.8 mg, 0.2 mmol) was dissolved in formic acid ( 5 mLj and left at room temperature for 15 min. The solvent was evaporated under reduced pressure and the crude product was purified by preparative thin-layer chromatography (silica1 gel, CH,CI,/MeOH, 95/5 under NH, atmosphere) to give (k)-uleine (2) (54 mg, 95 %)

Concise Synthesis of Spirocyclic, Bridged γ-Butyrolactones via Stereospecific, Dyotropic Rearrangements of β-Lactones Involving 1,2-Acyl and δ-Lactone Migrations

“…A plausible synchronous mechanism invokes a two-electron three-centered acylium intermediate 6 , reminiscent of transition states proposed for Friedel−Crafts acylation, or a carboxylate-stabilized, four-membered transition state 7 , both benefiting from a homoconjugated, carbonyl-assisted migration (frangomeric effect) (Figure ) . To the best of our knowledge, 1,2-acyl migrations are unprecedented in type I dyotropic processes.…”

“…One of the earliest examples of this rearrangement was the mutarotation of vicinal dibromides in steroidal systems first studied by Winstein and Barton . Seminal work by Mulzer employing Lewis acid mediated versions with β-lactone substrates provided insights into the relative migratory aptitude of electron-rich groups in these type I dyotropic rearrangements . A requirement for such a molecular rearrangement is an antiperiplanar relationship between the migrating group and the β-C−O σ-bond of the β-lactone.…”

Diastereo- and Enantioselective Synthesis of Bi- and Tricyclic N-Heterocycle-Fused β-Lactones

“…Attempted dyotropic rearrangement of β-lactone (±)- 8i with stoichiometric amounts of MgBr 2 ·OEt 2 , ,,, led to alternative conditions for decarboxylation (37%) providing alkene (±)- 21 albeit in low yield (Scheme ).…”

Pseudosymmetry withZ' = 4 in 1,3-propanesultone at 100K

“…The title compound was obtained as a product of a dyotropic ring-enlargement reaction of the isomeric /3-1actone, with the ester O and the trans-diaxial-positioned H atom migrating (Mulzer et al, 1997). The substance was isolated as the major reaction product and was separated from a minor isomer by high-performance liquid chromatography.…”