Katalytische, enantioselektive Synthesen von Diarylmethanolen und Allylalkoholen

In this research new, catalytic, enantioselective aryl transfer reactions to aldehydes for the synthesis of chiral diarylmethanols were developed. Diarylmethanols are important intermediates for the synthesis of pharmaceutically active compounds. In the foregoing research, it was found that, in presence of an appropriate catalyst, diarylmethanols could be synthesised by addition to aldehydes using a zinc reagent generated in situ from diphenyl- and diethylzinc. Of the catalysts tested, planar chiral organosilanols, which were produced in a multistep synthesis, smoothly effected the formation of diarylmethanols in good yields (up to 87%) and enantioselectivities (up to 91% ee). Other catalysts, which were applied in the asymmetric phenyl transfer, were N-substituted beta-amino alcohol derivatives, including either cis- or trans-beta-aminocyclohexanols and an open chain pyrrolinyl amino alcohol. The products were attained in good yields (73-99%) with enantioselectivities of between 6% and 87% ee. Triphenylborane was used as an alternative phenyl source to diphenylzinc, and this reagent, when transmetalated with diethylzinc to form a mixed zinc reagent, selectively transferred the phenyl group to the aldehyde. This reaction system, when used in the presence of a ferrocenyl-oxazoline catalyst, gave the diarylmethanols in very good yields and with excellent enantioselectivities of up to 98% ee. Aliphatic and heteroaromatic aldehydes could also be arylated under these conditions, and the products were obtained enantioselectively in good yields. The enantioselective phenylation of aromatic aldehydes with triphenylborane as a phenyl source was also catalysed by alpha-hydroxy-oxazolines. The products were generated with lower enantioselectivities of up to 43% ee and in yields of up to 91%. Diarylmethanols with substituents on both aryl groups could be synthesized by using aryl boronic acids as aryl sources and a ferrocenyl-oxazoline as a chiral catalyst. With this method it was possible to generate both enantiomers of one product using the same catalyst. The products were isolated with up to 95% ee and in up to 89% yield. Furthermore, a gram scale synthesis was possible using either triphenylborane or aromatic boronic acids as aryl sources. Beside the formation of diarylmethanols, an enantioselective vinylation of aldehydes for the generation of allylic alcohols was developed and optimised. Allylic alcohols are very important intermediates for the organic synthesis of natural products and pharmaceuticals. As such, alkenyl boronic acids were transmetalated with diethylzinc to form a mixed vinylzinc reagent. The use of additives, especially iso-propanol had a positive effect on yield and the enantioselectivity of the reaction, such that in the presence of a chiral catalyst the desired allylic alcohols were isolated in good yields (up to 79%) and enantioselectivities (up to 75% ee). An additional component of this research involved ethylation of an N-acylpyridinium salt with diethylzinc to furnish a 2,3-dihydropyridinone which, even after optimisation could only be isolated with an enantioselectivity of 11% ee. The arylation of 4-acetoxyacetidin-2-one was also of a great interest, since the products could be easily converted into beta-amino acids. Attention was, thus, mainly focused on the application of aryl boronic acids as aryl sources. However, the use of phenyl boronic acid gave the desired beta-lactam with an enantioselectivity of only 15% ee. Another objective of this work involved its application to the synthesis of chiral precursors of the Duloxetin and other NOS-inhibitors. Two chiral alcohol precursors to these compounds were synthesised in 72% and 55% yield and with 69% and 71% ee, respectively.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2006

Author dc:creator

• Schmidt, Frank

Contributors dc:contributor

• Bolm, Carsten

• info:eu-repo/classification/ddc/540
• Chemie
• Asymmetrische Synthese
• Katalyse
• Zink
• Chiralität
• Alkohole
• Allylalkohole
• Diarylmethanole
• Aminoalkohole
• Allyl Alcohols
• Diarylnethanols
• Amino Alcohols

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123250%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:61602