Titanium isopropoxide-mediated cis-selective synthesis of 3,4-substituted butyrolactones from CO₂

Abstract

Titanium-mediated 1,2-activation of Grignard reagents enables α and β insertion of carbon dioxide and arylaldehyde to prepare cis-3,4 butyrolactones.

Chemo- and Regioselective Alkylation of Pyridine N-Oxides with Titanacyclopropanes

“…Moreover, this reaction pattern also represents a novel pyridylative difunctionalization of olefins . It should be noted that only few electrophiles (H 2 O, NBS, I 2 , O 2 , RCHO) were found to react with the remaining C–Ti bond in the reported difunctionalization of titanacyclopropanes, where CO 2 usually acted as the first electrophile and did not react with the remaining C–Ti bond. , In sharp contrast, CO 2 acted as the second electrophile to react well with the remaining C–Ti bond in the present reactions. Also, ArNCO and ArCOCl successfully functionalized the remaining C–Ti bonds as a second electrophilic for the first time.…”

“…This addition can be formally regarded as a 3 + 3 cycloaddition process and formed a six-membered titanacycle intermediate ( 11 ). In previous difunctionalizations of Kulinkovich reagents and related reactions, five-membered titanacycle intermediates were proposed. , Moreover, in the C2–H alkylation of pyridine N -oxides with Wittig reagents, 1,1-diborylalkanes, and sulfonium ylides, the corresponding five-membered cyclic intermediates were also proposed. In contrast, a six-membered titanacycle intermediate ( 11 ) was reasonably suggested for the first time in the present reactions.…”

γ-Butyrolactone Synthesis from Allylic Alcohols Using the CO2 Radical Anion

“…A γ-metalated alcohol intermediate or analogous metallacycle can be carboxylated with CO 2 to yield the corresponding seven-membered metallacycle, which can then lead to γ-butyrolactones via intramolecular condensation. This intermediate can be alternatively synthesized through oxidative cyclization from alkenes, aldehydes, and CO 2 in a three-component reaction (Scheme a). − With substrates bearing an alkyne, carboxylation of the carbon nucleophile followed by cyclization can also furnish the products through π-acid metal catalysis mainly using Ag (Scheme b). , A zwitterionic intermediate known as TMM (trimethylenemethane), generally formed from methylene cyclopropane or 2-(acetoxymethyl)-3-(trimethylsilyl)­propene in the presence of a Pd(0) catalyst, can be carboxylated to yield the corresponding γ-butyrolactone (Scheme c). , Furthermore, terminal alkyne carboxylation, followed by trapping with a propargyl halide to construct the ester moiety and subsequent metal-catalyzed [2 + 2 + 2] cyclization, leads to γ-butyrolactones (Scheme d). , …”

Expeditious preparation of β-sec-alkyl vicinal amino alcohols used for chiral ligand synthesis

“…In line with this proposal, we set out to test the viability of the formation of (R)-2-amino-3-methylbutan-1-ol (5a) starting from the reaction of 1 with MeMgBr. 17,18 The reaction proceeded smoothly to afford a tertiary alcohol 2a, which was converted into alkene 3a in good yield via an elimination step. Subsequent hydrogenation of 3a and then hydrolysis of the product generated β-amino alcohol 5a in 91% yield over two steps.…”