19922-82-8Relevant articles and documents
Lipase mediated enzymatic kinetic resolution of phenylethyl halohydrins acetates: A case of study and rationalization
Fonseca, Thiago de Sousa,Vega, Kimberly Benedetti,da Silva, Marcos Reinaldo,de Oliveira, Maria da Concei??o Ferreira,de Lemos, Telma Leda Gomes,Contente, Martina Letizia,Molinari, Francesco,Cespugli, Marco,Fortuna, Sara,Gardossi, Lucia,de Mattos, Marcos Carlos
, (2020/02/18)
Racemic phenylethyl halohydrins acetates containing several groups attached to the aromatic ring were resolved via hydrolysis reaction in the presence of lipase B from Candida antarctica (Novozym 435). In all cases, the kinetic resolution was highly selective (E > 200) leading to the corresponding (S)-β-halohydrin with ee > 99 %. However, the time required for an ideal 50 % conversion ranged from 15 min for 2,4-dichlorophenyl chlorohydrin acetate to 216 h for 2-chlorophenyl bromohydrin acetate. Six chlorohydrins and five bromohydrins were evaluated, the latter being less reactive. For the β-brominated substrates, steric hindrance on the aromatic ring played a crucial role, which was not observed for the β-chlorinated derivatives. To shed light on the different reaction rates, docking studies were carried out with all the substrates using MD simulations. The computational data obtained for the β-brominated substrates, based on the parameters analysed such as NAC (near attack conformation), distance between Ser-O and carbonyl-C and oxyanion site stabilization were in agreement with the experimental results. On the other hand, the data obtained for β-chlorinated substrates suggested that physical aspects such as high hydrophobicity or induced change in the conformation of the enzymatic active site are more relevant aspects when compared to steric hindrance effects.
Tandem transfer hydrogenation-epoxidation of ketone substrates catalysed by alkene-tethered Ru(ii)-NHC complexes
Malan, Frederick P.,Singleton, Eric,Van Rooyen, Petrus H.,Landman, Marilé
supporting information, p. 8472 - 8481 (2019/06/14)
A series of nine cyclopentadienyl Ru(ii)-NHC complexes (1-9) have been synthesised by systematically varying the ligand and/or ligand substituents: η5-C5H4R′ (R′ = H, Me), EPh3 (E = P, As), NHC (Im, BIm), where NHC = Im(R)(R′) (R, R′ = Me, Bn, 4-NO2Bn, C2H4Ph, C4H7). Each of the Ru(ii)-NHC complexes features an N-alkenyl tether to attain bidentate NHC ligands. All complexes found application as catalysts in the tandem transfer hydrogenation and epoxidation reactions of carbonyl substrates. The catalytic activity of the complexes was shown to be similar, with efficiencies of up to 69% conversion after 18 hours and varying alcohol:epoxide selectivity for a variety of electronically diverse carbonyl substrates. Complex 3, with a nitro-containing substituent on the NHC ligand, was the only complex that showed preference for the alcohol product over the epoxide after 18 hours of reaction time.
One-pot synthesis of α-bromo- and α-azidoketones from olefins by catalytic oxidation with in situ-generated modified IBX as the key reaction
Chandra, Ajeet,Parida, Keshaba Nanda,Moorthy, Jarugu Narasimha
supporting information, p. 5827 - 5832 (2017/09/09)
Simple one-pot protocols for the syntheses of α-bromoketones and α-azidoketones starting from olefins have been developed by employing catalytic oxidation of the intermediary bromohydrins with in situ-generated modified IBX as the key reaction. The improved procedure involves initial formation of bromohydrin by the reaction of olefin with NBS in acetonitrile-water mixture (1:1) at rt followed by oxidation with in situ-generated 3,4,5,6-tetramethyl-2-iodoxybenzoic acid (TetMe-IBX), produced in catalytic amounts from 3,4,5,6-tetramethyl-2-iodobenzoic and Oxone. α-Bromoketones are further converted in the same pot to the corresponding α-azidoketones using NaN3/NaHCO3. The one-pot conversions are versatile for a variety of olefins that include cyclic as well as acyclic aliphatic olefins and electron-rich and electron-deficient styrenes. Chemoselective bromohydroxylation of electron-rich double bond and subsequent oxidation to the α-bromoketone is demonstrated for a substrate that contains both electron-rich and deficient double bonds.
Azidolysis of epoxides catalysed by the halohydrin dehalogenase from Arthrobacter sp. AD2 and a mutant with enhanced enantioselectivity: an (S)-selective HHDH
Mikleu?evi?, Ana,Primo?i?, Ines,Hrenar, Tomica,Salopek-Sondi, Branka,Tang, Lixia,Elenkov, Maja Majeri?
, p. 930 - 935 (2016/09/13)
Halohydrin dehalogenase from Arthrobacter sp. AD2 catalysed azidolysis of epoxides with high regioselectivity and low to moderate (S)-enantioselectivity (E?=?1–16). Mutation of the asparagine 178 to alanine (N178A) showed increased enantioselectivity towards styrene oxide derivatives and glycidyl ethers. Conversion of aromatic epoxides was catalysed by HheA-N178A with complete enantioselectivity, however the regioselectivity was reduced. As a result of the enzyme-catalysed reaction, enantiomerically pure (S)-β-azido alcohols and (R)-α-azido alcohols (ee???99%) were obtained.
Synthesis of optically active α-bromohydrins via reduction of α-bromoacetophenone analogues catalyzed by an isolated carbonyl reductase
Ren, Jie,Dong, Wenyue,Yu, Benqing,Wu, Qiaqing,Zhu, Dunming
body text, p. 497 - 500 (2012/07/28)
Enantiomerically pure (S)-α-bromohydrins were prepared by the reduction of α-bromoacetophenone analogues catalyzed by an isolated carbonyl reductase from Candida magnolia with high yield and excellent enantiomeric excess when methyl tert-butyl ether was employed as the co-solvent, while avoiding the formation of by-products. This provides a new approach to access these chiral α-bromohydrins which are of pharmaceutical importance.
Chemo- And stereodivergent preparation of terminal epoxides and bromohydrins through One-Pot biocatalysed reactions: Access to enantiopure Five- and Six-Membered N-Heterocycles
Bisogno, Fabricio R.,Cuetos, Anibal,Orden, Alejandro A.,Kurina-Sanz, Marcela,Lavandera, Ivan,Gotor, Vicente
supporting information; experimental part, p. 1657 - 1661 (2010/09/18)
Different enantiopure terminal epoxides or bromohydrins have chemoselectively been synthesised in one-pot starting from the corresponding a-bromo ketones through alcohol dehydrogenase (ADH)-catalysed processes adding an organic cosolvent and tuning appropriately the medium pH and the temperature. Thus, at neutral pH enantiopure bromohydrins were obtained while using basic conditions (pH 9.5-10) epoxides were isolated as the main product. Furthermore, by simple selection of the biocatalyst, chemo- and stereodivergent transformations were achieved to obtain, e.g., enantiopure prolinol or piperidin-3-ol.
Allyltin tribromide: A versatile reagent involved in the ring-opening of epoxides
Chen, Guohong,Wang, Xin,Jin, Xiaoqian,Liu, Lingyan,Chang, Weixing,Li, Jing
experimental part, p. 1294 - 1301 (2010/11/05)
This paper presents a versatile reagent for epoxide cleavage. The allyltin tribromide could act as a novel and easily prepared allylation reagent and halide atom donor to convert epoxides to the corresponding homoallyl alcohols and halohydrins in high yields with excellent regioselectivities under mild reaction conditions, respectively. It could also act as a Lewis acid to catalyze the ring opening reactions of epoxides with alcohols.
Dynamic kinetic resolution of racemic β-haloalcohols: Direct access to enantioenriched epoxides
Haak, Robert M.,Berthiol, Florian,Jerphagnon, Thomas,Gayet, Arnaud J. A.,Tarabiono, Chiara,Postema, Christiaan P.,Ritleng, Vincent,Pfeffer, Michel,Janssen, Dick B.,Minnaard, Adriaan J.,Feringa, Ben L.,De Vries, Johannes G.
supporting information; body text, p. 13508 - 13509 (2009/02/06)
The direct chemo-enzymatic DKR of racemic β-haloalcohols is reported, yielding the corresponding optically active epoxides in a single step. The mutant haloalcohol dehalogenase HheC Cys153Ser Trp249Phe is used for the asymmetric ring closure, whereas racemization of the remaining enantiomer of the haloalcohol is achieved using the new iridacycle 3, one of the most effective racemization catalysts to date for β-haloalcohols. Copyright
Chiral styrene oxides from α-haloacetophenones using NaBH4 and TarB-NO2, a chiral Lewis acid
Cordes, David B.,Kwong, Tracey J.,Morgan, Kellie A.,Singaram, Bakthan
, p. 349 - 351 (2007/10/03)
High enantioselectivities are obtained for the preparation of chiral styrene oxides through reduction of α-haloacetophenones using TarB-NO 2 reagent and the inexpensive and mild reducing agent NaBH 4. The epoxides are easily obtained in up to 95% ee through routine acid-base workup of the product alcohols. Either the (R) or (S) epoxide can be obtained by using the appropriate l- or d-tartaric acid starting material in the TarB-NO2 reagent.
Synthesis of β-adrenergic blockers (R)-(-)-nifenalol and (S)-(+)-sotalol via a highly efficient resolution of a bromohydrin precursor
Kapoor, Munish,Anand, Naveen,Ahmad, Khursheed,Koul, Surrinder,Chimni, Swapandeep S.,Taneja, Subhash C.,Qazi, Ghulam N.
, p. 717 - 725 (2007/10/03)
(R)- and (S)-2-bromo-1-(4-nitrophenyl)ethanol are precursors of important β-adrenergic receptor blocking drugs (R)-nifenalol and (S)-sotalol, respectively. Both were obtained in enantiomeric pure forms via a single highly efficient enzymatic transesterification reaction of (±)-2-bromo-1-(4- nitrophenyl)ethanol using immobilized lipase PS-C-II (E >1000; concn 200 g/L), while PS lipase completely failed to react. On the other hand, the hydrolytic method also produced enantiorich precursors though relatively less efficient (PS-C-II, E = 5.1). Out of all the approaches employed the transesterification method proved to be the most efficient.
