865357-14-8Relevant academic research and scientific papers
Lewis acid-lewis base-catalysed enantioselective addition of α-ketonitriles to aldehydes
Lundgren, Stina,Wingstrand, Erica,Moberg, Christina
, p. 364 - 372 (2007)
Additions of structurally diverse α-ketonitriles to aromatic and aliphatic prochiral aldehydes yielding highly enantioenriched acylated cyanohydrins were achieved using a combination of a titanium salen dimer and an achiral or chiral Lewis base. In most cases high yields and high enantioselectivities were observed. The ee was moderate in the initial part of the reaction but increased over time. This could be avoided, and higher ees obtained, by keeping the titanium complex, in the presence or absence of aldehyde and ketonitrile, at -40°C prior to the addition of the Lewis base. A mechanism initiated by nucleophilic attack of the tertiary amine at the carbonyl carbon atom of the ketonitile is supported by 13C labelling experiments.
Asymmetric synthesis of O-benzoyl cyanohydrins by reaction of aldehydes with benzoyl cyanide catalysed by BINOLAM-Ti(IV) complexes
Baeza, Alejandro,Najera, Carmen,Sansano, Jose M.,Saa, Jose M.
, p. 2385 - 2389 (2005)
The asymmetric cyanobenzoylation of aldehydes has been carried out for the first time, by reaction with benzoyl cyanide in a process catalysed by either (R)- or (S)-3,3′-bis(diethylaminomethyl)-1,1′-binaphthol BINOLAM-Ti(IV) complexes at room temperature and without additives. The reaction can be described as an overall cyano-O-benzoylation of aldehydes where a Lewis acid-Broensted base (LABB) dual role for the catalyst induced firstly the key enantioselective hydrocyanation, which is then followed by O-benzoylation furnishing enantioenriched O-benzoyl cyanohydrins.
Mechanistic studies on the enantioselective BINOLAM/titanium(IV)-catalyzed cyanobenzoylation of aldehydes: Part 1
Baeza, Alejandro,Najera, Carmen,Sansano, Jose M.,Saa, Jose M.
experimental part, p. 1282 - 1291 (2011/11/28)
The enantioselective titanium(IV)-catalyzed cyanobenzoylation of aldehydes using 1:1 BINOLAM/Ti(OiPr)4 mixtures as a precatalyst gave O-aroyl cyanohydrins 4 with good enantiomeric excesses. The standard optimization set carried out on the assumption of Curtin-Hammett behavior, led to no amelioration. Extensive experimental and computational studies were carried out with the purpose of identifying the key mechanistic aspects governing enantioselectivity. HCN and isopropyl benzoate were detected in the reacting mixtures. This as well as the reaction response to the presence of an exogenous base, and the failure to react in the presence of Binol/Ti(OiPr)4 mixtures, led us to propose, not a direct but an indirect process involving an enantioselective hydrocyanation step followed by O-benzoylation. Computational work carried out with mononuclear monomeric MM and dinuclear mixed dimer DlMD as catalysts support this mechanistic proposal. On the other hand, cyanobenzoylations carried out with 1:2 or higher 1:n (up to 1:5) BINOLAM/Ti(OiPr)4 mixtures appear to involve a reversal of the enantioselection. This, together with the fact that the benzoylation of the ligated iPrOH is a slow reaction, has led us to conclude that these cyanobenzoylations do not fit within the standard Curtin-Hammett kinetic scheme. Instead, such BINOLAM/Ti(OiPr)4 -catalyzed cyanobenzoylations of aldehydes rather behave as non-Curtin-Hammett kinetic schemes. Further computational analysis is needed in order to make a clear distinction between Curtin-Hammett and non-Curtin-Hammett kinetic frameworks.
