Molecular modification of anticholinergics as probes for muscarinic receptors. 2. Amino esters of .alpha.-methyltropic acid

Lu, Ming‐Chun; Shih, Lisa B.; Jae, Hwan Soo; Gearien, James E.; Thompson, E. B.

doi:10.1021/jm00385a028

Cited by 6 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, 31 , 32 and 33 were obtained from morpholinones 18 , 25 and 23 respectively (Scheme ). Comparison of the optical rotations of the acids 31 18 and 32 19 with reported values confirmed the “ R ” configuration. The formation of the “ R ” enantiomer also confirms the stereochemical outcome of the Prins reaction.…”

Section: Resultssupporting

confidence: 68%

Enantioselective Synthesis of Functionalized Quaternary Stereocenters

2015

View full text Add to dashboard Cite

An enantioselective synthesis of functionalized quaternary stereocenters was developed from amino alcohol derived (bromoalkylidene)morpholinones. Stereoselective cross‐coupling of the morpholinones with arylboronic acids or alkyl trifluoroborates provided a variety of disubstituted alkylidenemorpholinones. A highly stereoselective Prins reaction of the cross‐coupling products generated the target quaternary stereocenter. The Prins products are readily converted into a variety of acyclic, enantiomerically enriched, functionalized building blocks with a quaternary stereocenter.

show abstract

Section: Resultssupporting

confidence: 68%

Enantioselective Synthesis of Functionalized Quaternary Stereocenters

2015

View full text Add to dashboard Cite

show abstract

“…[11] The alcohol 3 was oxidized successively with ozone and hydrogen peroxide to a-methyltropic acid (4), a key intermediate for the synthesis of antispasmodics (Scheme 4). [12] In summary, an efficient nickel-catalyzed hydrovinylation of a-ketal derivatives of vinylarenes was developed. This reaction provides a practically useful and atom-economic method for the construction of multifunctional compounds with a quaternary carbon center.…”

mentioning

confidence: 99%

Nickel‐Catalyzed Highly Selective Hydrovinylation of α‐Ketals of Vinylarenes

Zhang¹,

Zhu²,

Qiao³

et al. 2008

Adv Synth Catal

View full text Add to dashboard Cite

A nickel-catalyzed hydrovinylation of aketal derivatives of vinylarenes has been developed, providing a new method for preparing functional olefins with a quarternary carbon center in high yields and selectivities.Keywords: C À C bond formation; functionalized olefins; hydrovinylation; nickel Carbon-carbon bond formation is the essence of organic synthesis and provides the foundation for generating complicated organic compounds from simpler ones. The transition metal-catalyzed hydrovinylation reaction (Scheme 1), the addition of a vinyl group and a hydrogen atom across a double bond, is an atomeconomical carbon-carbon bond formation reaction. [1] Owing to the abundant availability of starting materials the hydrovinylation reacion has received increasing attention in the fine chemical and pharmaceutical industries. In the past decades, several transition metal catalysts have been developed for hydrovinylation of unfunctionalized olefins such as vinylarenes, a-alkylvinylarenes, strained olefins and 1,3-dienes. [2] However, the examples of successful hydrovinylation of functionalized olefins, which would provide synthetically useful multifunctional compounds, are limited. In 1965, Alderson and co-workers [3] reported a hydrovinylation of methyl acrylate catalyzed by rhodium or ruthenium at high temperature and obtained a mixture of hydrovinylation product and the dimer of methyl acrylate. In the ruthenium hydride complexcatalyzed hydrovinylation of a,b-unsaturated ketones and esters Yi et al.[4] gained the hydrovinylation products with a double bond migration. Palladium [5] and nickel [6] catalysts with different ligands were also tested in the hydrovinylation of various functionalized olefins, however, low conversions or poor selectivities were generally obtained. As part of an effort to search for efficient catalysts for the hydrovinylation of functionalized olefins, herein we report a highly selective nickel-catalyzed hydrovinylation of a-ketal derivatives of vinylarenes.The hydrovinylation of 2-(1-phenylvinyl)-1,3-dioxolane (1a) was performed in CH 2 Cl 2 at room temperature using a nickel catalyst generated in situ from 2.5 mol% [NiA C H T U N G T R E N N U N G (allyl)Br] 2 , 5 mol% ligand, and 6 mol% NaBArF. [7] Firstly, the effect of phosphorus ligands was examined. With the ligand PPh 3 , a 90% conversion with 75% yield of hydrovinylation product (selectivity) and oligomers [8] were obtained (Table 1, entry 1). Very high selectivity (98%) was achieved by using the electron-rich trialkylphosphine ligand PA C H T U N G T R E N N U N G (nBu) 3 , but the conversion of reaction was low (40%) (entry 2). The negligible conversion in the reaction with the ligand PCy 3 indicated that a sterically hindered phosphine ligand is unfavourable for the hydrovinylation of 1a (entry 3). Systematic modification of the ligand PPh 3 revealed that the phosphonite L2 was the best choice of ligand, affording the hydrovinylation product in full conversion and 97% selectivity (entry 8). Use of two equivalents of ligand L2 o...

show abstract