A sustainable water-tolerant catalyst with enhanced Lewis acidity: Dual activation of Cp2TiCl2 via ligand and solvent

One-pot synthesis of benzo[b][1,4]diazepines via the carbonylative Sonogashira reaction and aza-Michael addition cyclocondensation

“…First and foremost, we started our investigation using iodobenzene 1a , phenylacetylene 2a and o -phenylenediamine 3a as model substrates under a CO atmosphere (Table 1). Fortunately, the desired product 4aaa was obtained in 36% yield when the reaction was conducted in standard conditions, which have been previously reported 32 (Table 1, entry 1). The experimental results prove that our idea is feasible.…”

“…This is mainly because ethanol also participates in the reaction as a ligand. 32,38 Furthermore, by increasing the amount of Cp 2 TiCl 2 and m -phthalic acid from 2 mol% to 10 mol%, the yield of 4aaa increased to 62% (Table 1, entries 6 and 7). In our previous research on Cp 2 TiCl 2 , we found that the Cp ring easily leaves and loses its activity under alkaline conditions.…”

“…[20][21][22] Although the synthetic methodology of benzodiazepines has progressed in recent decades, the development of catalytic methods with high step-economy using simply available chemicals still draws significant attention from both academia and the pharmaceutical industry. [23][24][25][26][27][28][29][30][31][32] Our group recently developed a unique N-heterocyclic carbene palladium with triazine wingtips (T-NHC-Pd)-catalysed carbonylation Sonogashira reaction, synthesizing 1,3-ynones with ppm-level catalyst loading. 33 1,3-Ynones as Michael acceptors with versatile reactivity have been demonstrated to be facile synthons for constructing a variety of heterocycles and carbocycles.…”

“…In addition, it contains moderately active –COOH ligands, ensuring its high catalytic activity. 32 Then, 1,3-ynone is activated by the newly formed titanocene species, facilitating the Michael addition with o -phenylenediamine. After that, the carbonyl group of the Michael adduct is attacked by another amino group to form N , O -acetal.…”

Natural Amino Acid L‐Phenylalanine Coordinated Zirconocene Complex as Bifunctional Catalyst for the Synthesis of 1,5‐Benzothiazepines

“…Compared with some well-known tetravalent IVB Lewis acid catalyst (LA), such as TiCl 4 , [1] Ti(O-iPr) 4 , [2] titanocene/ zirconocene, [3] have been proven more diversified, efficient, and practical for CÀ C, CÀ N formation reactions, [4] due to their water compatibility, [5] tunable Lewis acidity, [6] as well as, in particular, possible additional catalytic effect by the introduction of a second catalytic site on ligand. [7] In 2014, our group disclose the first titanocene-based binary acid catalyst, where the Lewis acidic titanium center and extra Brønsted acidic (BA) functional group on its ligand may work cooperatively activating the two substrates, assuring the successful proceeding of intermolecular Mannich reaction.…”