5406-39-3Relevant academic research and scientific papers
Umpolung Strategy for Arene C?H Etherification Leading to Functionalized Chromanes Enabled by I(III) N-Ligated Hypervalent Iodine Reagents
Mikhael, Myriam,Guo, Wentao,Tantillo, Dean J.,Wengryniuk, Sarah E.
supporting information, p. 4867 - 4875 (2021/09/14)
The direct formation of aryl C?O bonds via the intramolecular dehydrogenative coupling of a C?H bond and a pendant alcohol represents a powerful synthetic transformation. Herein, we report a method for intramolecular arene C?H etherification via an umpoled alcohol cyclization mediated by an I(III) N-HVI reagent. This approach provides access to functionalized chromane scaffolds from primary, secondary and tertiary alcohols via a cascade cyclization-iodonium salt formation, the latter providing a versatile functional handle for downstream derivatization. Computational studies support initial formation of an umpoled O-intermediate via I(III) ligand exchange, followed by competitive direct and spirocyclization/1,2-shift pathways. (Figure presented.).
Access to Trisubstituted Fluoroalkenes by Ruthenium-Catalyzed Cross-Metathesis
Nouaille, Augustin,Pannecoucke, Xavier,Poisson, Thomas,Couve-Bonnaire, Samuel
supporting information, p. 2140 - 2147 (2021/03/06)
Although the olefin metathesis reaction is a well-known and powerful strategy to get alkenes, this reaction remained highly challenging with fluororalkenes, especially the Cross-Metathesis (CM) process. Our thought was to find an easy accessible, convenient, reactive and post-functionalizable source of fluoroalkene, that we found as the methyl 2-fluoroacrylate. We reported herein the efficient ruthenium-catalyzed CM reaction of various terminal and internal alkenes with methyl 2-fluoroacrylate giving access, for the first time, to trisubstituted fluoroalkenes stereoselectively. Unprecedent TON for CM involving fluoroalkene, up to 175, have been obtained and the reaction proved to be tolerant and effective with a large range of olefin partners giving fair to high yields in metathesis products. (Figure presented.).
Ir-catalyzed tandem hydroformylation-transfer hydrogenation of olefins with (trans-/cis-)formic acid as hydrogen source in presence of 1,10-phenanthroline
Chen, Xiao-Chao,Gao, Han,Liu, Lei,Liu, Ye,Lu, Yong,Xia, Fei,Yang, Shu-Qing
, p. 183 - 193 (2020/04/08)
The one-pot tandem hydroformylation-reduction to synthesize alcohols from olefins is in great demand but suffering from low yields, poor selectivity and harsh condition. Herein, 1,10-phenanthroline (L1) modified Ir-catalyst proved to exhibit multiple cata
Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols
Aleku, Godwin A.,Leys, David,Roberts, George W.
, p. 3927 - 3939 (2020/07/09)
We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates. E. coli cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99percent conversion. This was supported by the broad substrate scope of E. coli endogenous alcohol dehydrogenase (ADH), as well as the unexpected CC bond reducing activity of E. coli cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant E. coli cells. An alternative one-pot in vitro two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99percent conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the in vitro system, affording up to 85percent isolated yield.
Iridium Complex-Catalyzed C2-Extension of Primary Alcohols with Ethanol via a Hydrogen Autotransfer Reaction
Kobayashi, Masaki,Itoh, Satoshi,Yoshimura, Keisuke,Tsukamoto, Yuya,Obora, Yasushi
, p. 11952 - 11958 (2020/10/23)
The development of a C2-extension of primary alcohols with ethanol as the C2 source and catalysis by [Cp*IrCl2]2 (where Cp? = pentamethylcyclopentadiene) is described. This new extension system was used for a range of benzylic alcohol substrates and for aliphatic alcohols with ethanol as an alkyl reagent to generate the corresponding C2-extended linear alcohols. Mechanistic studies of the reaction by means of intermediates and deuterium labeling experiments suggest the reaction is based on hydrogen autotransfer.
Regulating Hydrogenation Chemoselectivity of α,β-Unsaturated Aldehydes by Combination of Transfer and Catalytic Hydrogenation
Zhou, Yangyang,Li, Zihao,Liu, Yanbo,Huo, Jia,Chen, Chen,Li, Qiling,Niu, Songyang,Wang, Shuangyin
, p. 1746 - 1750 (2020/02/25)
Two hydrogenation mechanisms, transfer and catalytic hydrogenation, were combined to achieve higher regulation of hydrogenation chemoselectivity of cinnamyl aldehydes. Transfer hydrogenation with ammonia borane exclusively reduced C=O bonds to get cinnamyl alcohol, and Pt-loaded metal–organic layers efficiently hydrogenated C=C bonds to synthesize phenyl propanol with almost 100 % conversion rate. The hydrogenation could be performed under mild conditions without external high-pressure hydrogen and was applicable to various α,β-unsaturated aldehydes.
Tandem IBX-Promoted Primary Alcohol Oxidation/Opening of Intermediate β,γ-Diolcarbonate Aldehydes to (E)-γ-Hydroxy-α,β-enals
Kumari, Anupama,Gholap, Sachin P.,Fernandes, Rodney A.
, p. 2278 - 2290 (2019/06/17)
A tandem IBX-promoted oxidation of primary alcohol to aldehyde and opening of intermediate β,γ-diolcarbonate aldehyde to (E)-γ-hydroxy-α,β-enal has been developed. Remarkably, the carbonate opening delivered exclusively (E)-olefin and no over-oxidation of γ-hydroxy was observed. The method developed has been extended to complete the stereoselective total synthesis of both (S)- and (R)-coriolides and d-xylo- and d-arabino-C-20 guggultetrols.
Carbene-Catalyzed α-Carbon Amination of Chloroaldehydes for Enantioselective Access to Dihydroquinoxaline Derivatives
Huang, Ruoyan,Chen, Xingkuan,Mou, Chengli,Luo, Guoyong,Li, Yongjia,Li, Xiangyang,Xue, Wei,Jin, Zhichao,Chi, Yonggui Robin
supporting information, p. 4340 - 4344 (2019/06/14)
An NHC-catalyzed α-carbon amination of chloroaldehydes was developed. Cyclohexadiene-1,2-diimines are used as amination reagents and four-atom synthons. Our reaction affords optically enriched dihydroquinoxalines that are core structures in natural products and synthetic bioactive molecules.
Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate, a muscarinic receptor antagonist with anti-inflammatory activity
Yamashita, Yasunobu,Tanaka, Ken-ichiro,Yamakawa,Asano,Kanda, Yuki,Takafuji,Kawahara, Masahiro,Takenaga, Mitsuko,Fukunishi, Yoshifumi,Mizushima
supporting information, p. 3339 - 3346 (2019/06/18)
The treatment for patients with chronic obstructive pulmonary disease (COPD) usually involves a combination of anti-inflammatory and bronchodilatory drugs. We recently found that mepenzolate bromide (1) and its derivative, 3-(2-hydroxy-2, 2-diphenylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (5), have both anti-inflammatory and bronchodilatory activities. We chemically modified 5 with a view to obtain derivatives with both anti-inflammatory and longer-lasting bronchodilatory activities. Among the synthesized compounds, (R)-(–)-12 ((R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octane bromide) showed the highest affinity in vitro for the human muscarinic M3 receptor (hM3R). Compared to 1 and 5, (R)-(–)-12 exhibited longer-lasting bronchodilatory activity and equivalent anti-inflammatory effect in mice. The long-term intratracheal administration of (R)-(–)-12 suppressed porcine pancreatic elastase-induced pulmonary emphysema in mice, whereas the same procedure with a long-acting muscarinic antagonist used clinically (tiotropium bromide) did not. These results suggest that (R)-(–)-12 might be therapeutically beneficial for use with COPD patients given the improved effects seen against both inflammatory pulmonary emphysema and airflow limitation in this animal model.
Highly pH-Dependent Chemoselective Transfer Hydrogenation of α,β-Unsaturated Aldehydes in Water
Luo, Nianhua,Liao, Jianhua,Ouyang, Lu,Wen, Huiling,Liu, Jitian,Tang, Weiping,Luo, Renshi
, p. 3025 - 3031 (2019/08/30)
The pH-dependent selective Ir-catalyzed hydrogenation of α,β-unsaturated aldehydes was realized in water. Using HCOOH as the hydride donor at low pH, the unsaturated alcohol products were obtained exclusively, while the saturated alcohol products were formed preferentially by employing HCOONa as the hydride donor at high pH. A wide range of functional groups including electron-rich as well as electron-poor substituents on the aryl group of α,β-unsaturated aldehydes can be tolerated, affording the corresponding products in excellent yields with high TOF values. High selectivity and yields were also observed for α,β-unsaturated aldehydes with aliphatic substituents. Our mechanistic investigations indicate that the pH value is critical to the chemoselectivity.
