A convenient titanium-mediated intermolecular alkyne–carbonate coupling reaction

A New Chemoenzymatic Synthesis of the Chiral Key Intermediate of the Antiepileptic Brivaracetam

“…The Perkin condensation between benzaldehyde and valeric anhydride afforded the ( E )-2-benzylidenpentanoate acid ( 10 ) that was transformed into the corresponding ethyl ester 11 (53% yield from benzaldehyde) [ 22 ]. LiAlH 4 in tetrahydrofuran, at reflux, afforded, by simultaneous reduction of the ester and of the double bond, the desired alcohol 8 in 69% yield.…”

“…R f 0.83 (toluene/ethyl acetate 9:1). 1 H-NMR [ 22 ]: 7.65 (s, 1H, CH=), 7.30–7.41 (m, 5H, Ar), 4.27 (q, J = 7.1 Hz, 2H, CH 2 CH 3 ), 2.49 (m, 2H, H-3), 1.53–1.62 (m, 2H, H-4), 1.35 (t, 3H, J = 7.1 Hz, CH 3 CH 2 ), 0.96 (t, 3H, J = 7.3 Hz, H-5). 13 C-NMR: 168.5 (C-1), 138.6 (PhCH=), 136.0 (Ar), 133.9 (C-2), 129.2, 128,4, 128.2 (Ar), 60.7 (OCH 2 CH 3 ), 29.5 (C-3), 22.6 (C-4), 14.3 ( C H 3 CH 2 ), 14.2 (C-5).…”

Regioselective Synthesis of Enones via a Titanium-Promoted Coupling of Unsymmetrical Alkynes with Weinreb Amides

“…13 Six expanded this work to include the formation of α,β-unsaturated carboxylic acids and esters via an intermolecular titanium-mediated reductive coupling of alkynes with carbon dioxide 14 and carbonates (Scheme 1b). 15 Complementarily, zirconocene-mediated couplings of alkynes with chloroformates 16 and carbon dioxide 17 have also been reported. Surprisingly, the use of group IV metallacycles to form enones from alkynes has not been reported.…”

“…Stemming from the seminal work of Kulinkovich on the cyclopropanation of esters, Sato demonstrated that diisopropoxytitanacyclopropenes undergo intramolecular nucleophilic acyl substitution with carbonates (Scheme a) . Six expanded this work to include the formation of α,β-unsaturated carboxylic acids and esters via an intermolecular titanium-mediated reductive coupling of alkynes with carbon dioxide and carbonates (Scheme b) . Complementarily, zirconocene-mediated couplings of alkynes with chloroformates and carbon dioxide have also been reported.…”

Titanium‐Mediated Synthesis of Spirocyclic NH‐Azetidines from Oxime Ethers

“…[10] We became attracted to the idea that Kulinkovich-like reaction conditions could be employed to synthesize the desired 1-azaspiro [3.5]nonane heterocyclic scaffolds. [11] The standard Kulinkovich reaction utilizes esters and aG rignard reagent to synthesize cyclopropanols through at itanacyclopropane intermediate (Scheme 1B4). [12] Several variations of this reaction exist, including ligand exchange with olefins and reactions of amides and nitriles with aG rignard coupling partner to form cyclopropanols and cyclopropyl amines, respectively (Scheme 1B5a nd 6).…”