- Green synthesis method of polyaryl substituted methanol
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The invention relates to a green synthesis method of polyaryl substituted methanol, in particular to a method for efficiently synthesizing polyaryl substituted methanol in a polar aprotic solvent under the condition of an oxidizing agent by taking polyaryl substituted methane as a raw material and alkali as an additive. The method provided by the invention is green and environment-friendly, avoids using expensive metal catalysts, and has the advantages of low cost, few reaction steps, short time, high yield and the like.
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Paragraph 0127-0131; 0162-0166
(2021/04/17)
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- Atroposelective Synthesis of Axially Chiral Styrenes via an Asymmetric C–H Functionalization Strategy
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Axially chiral styrenes, which exhibit a chiral axis between a substituted alkene and an aromatic ring, have been largely overlooked. The hurdle is the lower barriers to rotation compared with that of their biaryl counterparts, rendering their asymmetric synthesis more difficult. We report herein the highly atroposelective synthesis via a C?H functionalization strategy of axially chiral styrenes with an open-chained alkene. Various axially chiral styrenes were produced by Pd(II)-catalyzed C?H alkenylation and alkynylation in good yields (up to 99%) and enantioselectivities (up to 99% ee) by using L-pyroglutamic acid as an inexpensive chiral ligand. The potent application of the styrene atropisomers is demonstrated by a Co(III)-catalyzed enantioselective C?H amidation of ferrocene with axially chiral styrene-type acid as chiral ligand. Experimental and computational studies were conducted to elucidate the reaction mechanism. The chiral induction model of the enantioselectivity-determining C?H bond activation step was also provided based on DFT calculations. Atropisomerism, which stems from the hindered rotation around a chiral axis, is widely present in natural products, pharmaceuticals, and chiral catalysts or ligands. In contrast to the well-investigated biaryl atropisomers, the asymmetric synthesis of axially chiral styrenes bearing a chiral axis between an alkene and an aromatic ring remains a significant challenge. Here, we report a highly atroposelective synthesis of styrene atropisomers with open-chained alkene by asymmetric C?H functionalization by using available L-pyroglutamic acid as a chiral ligand. This strategy enables rapid access to a broad range of enantio-enriched axially chiral styrenes under mild conditions in an atom- and step-economical manner. The resulting axially chiral styrenes are important precursors for further elaborations, including the transformation into axially chiral styrene-type acids, which were demonstrated to be efficient chiral ligands in Co(III)-catalyzed enantioselective C?H amidation reactions. An asymmetric C–H functionalization strategy with L-pGlu-OH as chiral ligand has been developed for the atroposelective synthesis of styrene atropisomers with open-chained alkene. The strategy allows quick access to a wide range of enantio-enriched axially chiral styrenes in high yields and enantioselectivities. The axially chiral styrene-derived chiral acids have been demonstrated to be an efficient type of chiral ligands in Co(III)-catalyzed enantioselective C?H amidation reactions.
- Jin, Liang,Yao, Qi-Jun,Xie, Pei-Pei,Li, Ya,Zhan, Bei-Bei,Han, Ye-Qiang,Hong, Xin,Shi, Bing-Feng
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supporting information
p. 497 - 511
(2020/02/20)
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- Transition-Metal Free Chemoselective Hydroxylation and Hydroxylation-Deuteration of Heterobenzylic Methylenes
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We developed an approach for direct selective hydroxylation of heterobenzylic methylenes to secondary alcohols avoiding overoxidation to ketones by using a KOBu-t/DMSO/air system. Most reactions could reach completion in several minutes to give hydroxylated products in 41-76% yields. Using DMSO-d6, this protocol resulted in difunctionalization of heterobenzylic methylenes to afford α-deuterated secondary alcohols (>93% incorporation). By employing this method, active pharmaceutical ingredients carbinoxamine and doxylamine were synthesized in two steps in moderate yields.
- Fu, Yiwei,Li, Hao,Liu, Yonghai,Mang, Zhiguo,Shi, Lei,Sun, Chengyu,Yu, Yang
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supporting information
p. 8127 - 8131
(2020/11/03)
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- Ligand-Free Iridium-Catalyzed Dehydrogenative ortho C?H Borylation of Benzyl-2-Pyridines at Room Temperature
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A convenient and ligand-free iridium-catalyzed dehydrogenative ortho C?H borylation of benzyl-2-pyridines has been developed. The reaction proceeds smoothly at room temperature using pinacolborane as a borylating reagent in the presence of catalytic amount of [IrOMe(COD)]2. The reaction is compatible with many functional groups, providing a vast array of ortho borylated products in moderate to excellent yields with excellent selectivities. (Figure presented.).
- Yang, Yuhuan,Gao, Qian,Xu, Senmiao
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supporting information
p. 858 - 862
(2019/01/04)
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- Conformational Dynamics-Guided Loop Engineering of an Alcohol Dehydrogenase: Capture, Turnover and Enantioselective Transformation of Difficult-to-Reduce Ketones
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Directed evolution of enzymes for the asymmetric reduction of prochiral ketones to produce enantio-pure secondary alcohols is particularly attractive in organic synthesis. Loops located at the active pocket of enzymes often participate in conformational changes required to fine-tune residues for substrate binding and catalysis. It is therefore of great interest to control the substrate specificity and stereochemistry of enzymatic reactions by manipulating the conformational dynamics. Herein, a secondary alcohol dehydrogenase was chosen to enantioselectively catalyze the transformation of difficult-to-reduce bulky ketones, which are not accepted by the wildtype enzyme. Guided by previous work and particularly by structural analysis and molecular dynamics (MD) simulations, two key residues alanine 85 (A85) and isoleucine 86 (I86) situated at the binding pocket were thought to increase the fluctuation of a loop region, thereby yielding a larger volume of the binding pocket to accommodate bulky substrates. Subsequently, site-directed saturation mutagenesis was performed at the two sites. The best mutant, where residue alanine 85 was mutated to glycine and isoleucine 86 to leucine (A85G/I86L), can efficiently reduce bulky ketones to the corresponding pharmaceutically interesting alcohols with high enantioselectivities (~99% ee). Taken together, this study demonstrates that introducing appropriate mutations at key residues can induce a higher flexibility of the active site loop, resulting in the improvement of substrate specificity and enantioselectivity. (Figure presented.).
- Liu, Beibei,Qu, Ge,Li, Jun-Kuan,Fan, Wenchao,Ma, Jun-An,Xu, Yan,Nie, Yao,Sun, Zhoutong
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p. 3182 - 3190
(2019/05/15)
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- Iridium-Catalyzed Highly Enantioselective Transfer Hydrogenation of Aryl N-Heteroaryl Ketones with N-Oxide as a Removable ortho-Substituent
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A highly enantioselective transfer hydrogenation of non-ortho-substituted aryl N-heteroaryl ketones, using readily available chiral diamine-derived iridium complex (S,S)-1f as a catalyst and sodium formate as a hydrogen source in a mixture of H2O/i-PrOH (v/v = 1:1) under ambient conditions, is described. The chiral aryl N-heteroaryl methanols were obtained with up to 98.2% ee by introducing an N-oxide as a removable ortho-substituent. In contrast, no more than 15.1% ee was observed in the absence of an N-oxide moiety. Furthermore, the practical utility of this protocol was also demonstrated by gram-scale asymmetric synthesis of bepotastine besilate in 51% total yield and 99.9% ee.
- Liu, Qixing,Wang, Chunqin,Zhou, Haifeng,Wang, Baigui,Lv, Jinliang,Cao, Lu,Fu, Yigang
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p. 971 - 974
(2018/02/23)
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- Bifunctional Oxo-Tethered Ruthenium Complex Catalyzed Asymmetric Transfer Hydrogenation of Aryl N-Heteroaryl Ketones
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A facile asymmetric transfer hydrogenation of ortho-substituted aryl N-heteroaryl ketones and non-ortho-substituted N-oxide of aryl N-heteroaryl ketones using a readily available oxo-tethered ruthenium complex as a catalyst and sodium formate as a hydrogen source in an aqueous solution has been discovered. A variety of chiral aryl N-heteroaryl methanols were obtained with up to 99.9% ee.
- Wang, Baigui,Zhou, Haifeng,Lu, Guoren,Liu, Qixing,Jiang, Xiaolan
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p. 2094 - 2097
(2017/04/28)
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- Rhodium Catalyzed Asymmetric Hydrogenation of 2-Pyridine Ketones
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Catalyzed by [Rh(COD)Binapine]BF4, the asymmetric hydrogenation of 2-pyridine ketones has been achieved with excellent enantioselectivities (enantiomeric excesses up to 99%) under mild conditions. This method is suitable for various kinds of 2-pyridine ketones and their derivatives. A number of enantiomerically pure chiral 2-pyridine-aryl/alkyl alcohols were prepared through hydrogenation, which can be used directly in organic synthesis.
- Yang, Hailong,Huo, Ningning,Yang, Ping,Pei, Hao,Lv, Hui,Zhang, Xumu
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p. 4144 - 4147
(2015/09/15)
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- Iron-catalyzed C-H bond functionalization for the exclusive synthesis of pyrido[1,2-a]indoles or triarylmethanols
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The efficient and selective iron-catalyzed C-H activation of 2-benzhydrylpyridine derivatives was employed for the preparation of pyrido[1,2-a]indoles through an intramolecular C-H amination reaction. In the presence of molecular oxygen as the sole oxidant, the same 2-benzhydrylpyridines were also used for the synthesis of the corresponding tertiary alcohols. In these approaches, the iron catalyst was used to selectively activate the C(sp2)-H bond of 2-benzhydrylpyridine, in the case of the intramolecular ring-closing C-H amination reaction in which the pyridine nitrogen atom was a directing group as well as a nucleophile, and the C(sp3)-H bond of the same compound, in the case of the oxidation reaction to give the corresponding triaryl carbinol.
- Karthikeyan, Iyyanar,Sekar, Govindasamy
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supporting information
p. 8055 - 8063
(2015/01/09)
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- Chiral organomagnesiates as dual reagents for bromine-magnesium exchange of 2-bromopyridine and access to chiral α-substituted 2-pyridylcarbinols
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New chiral ligand containing butyl and dibutylmagnesiates have been prepared from a range of ligands and their reactivity studied. The reagents were generally efficient in promoting the clean bromine-magnesium exchange of 2-bromopyridine at room temperature and the subsequent reaction with aldehydes to afford α-substituted 2-pyridylcarbinols in good yields. (R,R)-TADDOLate proved to be the best ligand, leading to acceptable to good enantioselectivities. To the best of our knowledge this is the first example of an organomagnesiate-induced halogen-metal exchange followed by an enantioselective addition.
- Catel, Delphine,Chevallier, Floris,Mongin, Florence,Gros, Philippe C.
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supporting information; experimental part
p. 53 - 57
(2012/02/06)
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- Pyridylmagnesiates: Generation by bromine-metal exchange and enantioselective addition to aldehydes
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Butyl and dibutylmagnesiates incorporating chiral ligands have been prepared and their reactivity studied. The reagents were efficient to promote the clean bromine-magnesium exchange of azinyl bromides at room temperature and subsequent reaction with aldehydes affording pyridylcarbinols. (R,R)-TADDOL-based dibutylmagnesiate was the best reagent leading to acceptable to good enantioselectivities, depending on the substrate and on the aldehyde substitution. This is the first example of enantioselective addition of in situ generated pyridylmagnesiate to carbonyl electrophiles.
- Catel, Delphine,Payen, Olivier,Chevallier, Floris,Mongin, Florence,Gros, Philippe C.
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experimental part
p. 4018 - 4028
(2012/07/28)
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