38465-16-6Relevant articles and documents
Chelation-directed remote: Meta -C-H functionalization of aromatic aldehydes and ketones
Xie, Shuguang,Li, Sen,Ma, Wenqian,Xu, Xiaohua,Jin, Zhong
supporting information, p. 12408 - 12411 (2019/10/19)
We disclose herein the development of a versatile 1,2-diol directing template for palladium-catalyzed remote meta-C-H functionalization of aromatic aldehydes and ketones. In situ-generation of acetals and ketals, as well as removal afterwards, makes the C-H bond functionalization process more straightforward and efficient. This also represents the first example of chelation-directed meta-C-H functionalization of aromatic aldehydes and ketones.
Efficient chemoenzymatic synthesis of (RS)-, (R)-, and (S)-bunitrolol
Banoth, Linga,Chandarrao, Bhukya,Pujala, Brahmam,Chakraborti, Asit K.,Banerjee
, p. 479 - 488 (2014/03/21)
A new chemical and the first chemoenzymatic synthesis of β-adrenergic receptor blocking agent bunitrolol is reported in racemic (RS) and enantioenriched forms (R and S). The intermediates (R)- and (S)-1-chloro-3-(2- cyanophenoxy)propan-2-ol intermediates were synthesized from the corresponding racemic alcohol through enzymatic kinetic resolution. The commercial available lipases PS-C and CCL exhibited complementary enantioselectivity during transesterification of the racemic alcohol with vinyl acetate affording the (R)-alcohol along with (S)-acetate and the (S)-alcohol along with (R)-acetate, respectively, and represent an example of enzymatic switch for reversal of enantioselectivity. The effects of various reaction parameters, such as temperature, time, substrate and enzyme concentration, and reaction medium, on the activity and enantioselectivity were optimized. The (R)- and (S)-alcohols were converted into (S)-and and (R)-bunitrolol, respectively, by treatment with tert-butylamine. The (R)- and (S)-acetates, obtained enzymatically were deacetylated to the corresponding alcohol by chemical hydrolysis and further converted into (S)-and and (R)-bunitrolol by chemical means. This is the first chemoenzymatic synthesis of both of the enantiomers of the drug. (RS)-, (R)-, and (S)-Bunitrolol were also synthesized following the 'all chemical' routes from (RS)-, (R)-, and (S)-epichlorohydrin via the corresponding (RS)-, (S)-, and (R)-2-cyanoglycidyl ether and the (RS)-, (R)-, and (S)-1-chloro-3-(2- cyanophenoxy)propan-2-ol intermediates with improved overall yields and better enantiomeric excesses compared to the reported processes.
Improvement and simplification of synthesis of 3-aryloxy-1,2-epoxypropanes using solvent-free conditions and microwave irradiations. Relation with medium effects and reaction mechanism
Pchelka, Beata K.,Loupy, Andre,Petit, Alain
, p. 10968 - 10979 (2007/10/03)
Some 3-aryloxy-1,2-epoxypropanes, interesting as potential synthons in β-adrenergic receptor antagonists preparation, were obtained in excellent yields (65-96% within 2-17 min) by microwave activation (monomode system) using solid-liquid solvent-free phase transfer catalysis (PTC). The best results for the O-alkylation of some phenols with epichlorohydrin were obtained using TBAB and NaOH/K2CO3 (1:4 mol/mol) as phase transfer catalyst and more acceptable basic system, respectively. These new procedure is compared with classical methods. Significant specific microwave effect (non-purely thermal) was evidenced in all cases. They were discussed in terms of reaction medium and mechanism, taking into account the variations in polarity of the systems.
