Preparation and Utilization of SF5-Containing Building Blocks
Zusammenfassung der Projektergebnisse
The chemistry of organic fluorine compounds has developed most rapidly in recent decades, despite the fact that fluorine is “foreign” to most living organisms and only a dozen fluorinecontaining natural products are known. In sharp contrast, plenty of synthetic fluoroorganics hold prestigious positions in almost all areas of chemistry, particularly in medicinal and agricultural fields, and many other disciplines like material sciences. Besides fluorine as a substituent itself and the trifluoromethyl (CF3) group, the pentafluorosulfanyl (SF5) substituent came into the focus and was characterized as “super CF3 group”, due to the extraordinary physical-chemical and biological properties of compounds containing this group. However, mostly aromatic SF5-compounds were investigated, because of the lack of aliphatic building blocks. This project was designed to make available new SF5-containing reagents and building blocks and to depict opportunities for application in synthetic organic chemistry having in mind also biological activity. The two collaborating research groups, developed new syntheses of SF5CF2C(O)Cl, SF5CH2C(O)Cl, SF5CF2I and SF5CF2CF2Br and used these reagents in different organic reactions, mostly electrophilic or radial additions and rearrangements. The acid chloride SF5CF2C(O)Cl was used to prepare corresponding esters and amides starting from suitable alcohols or amines. Addition products of aromatic or heteroaromatic amines could be cyclized to polycyclic heterocycles bearing the new SF5CF2-substituent. Moreover, the acid chloride was added to electron-rich alkenes such as enol ethers and the products were applied for downstream chemistry. Reduction of SF5CF2-substituted α,β-unsaturated ketones, however, did not lead to the target SF5CF2-substituted allylic alcohols, but provided CF3-substituted products. A plausible explanation of the mechanism of this new and unexpected reaction sequence was found. Initially intended [3,3]-sigmatropic rearrangements with allylic alcohols containing a vinylic SF5CF2-group failed because of instability of this group under different conditions. In contrast, [3,3]-sigmatropic rearrangements like the Ireland-Claisen variation were successful with the SF5CH2C(O) moiety as ester component. In this way, a series of α-SF5-substituted long-chain carboxylic acid derivatives, including those derived from cinnamyl alcohols, were synthesized for the first time. Based on the discovery that these intermediates were stable under the reaction conditions (NMR), Mukaiyama aldol reactions of SF5CF2C(O)OR esters with substituted benzaldehydes were shown to be anti-selective when mediated by a dialkyl chloroborane reagent, while synproducts were formed selectively in silicon-mediated reactions. Finally, the introduction of SF5(CF2)n moieties into unsaturated compound was investigated using radical reactions. Triethylborane was shown to be the most useful initiator for these reactions. The SF5CF2CF2∙ radical did react smoothly with enol ethers and strained dieses like norbornadiene and cycloocta-1,5-diene showing the electrophilic character of this radical, which failed to react with ordinary alkenes, allyl- and vinyl ethers or allyl acetate. In contrast, α,β-unsaturated ketones reacted in conjugate 1,4-addition providing β-(CF2)2SF5-substituted ketones showing that the SF5CF2CF2∙ radical has also nucleophilic properties due to the n-electron donating character of fluorine. The reactivity of the SF5CF2∙ radical was slightly different. Expectedly, it was smoothly added to enol ethers. However, this radical did also react with ordinary alkenes, while it did not react with α,β-unsaturated ketones. The nature of the different reactivity of formally very similar radicals was not investigated yet.
Projektbezogene Publikationen (Auswahl)
- New Approach to α-Pentafluorosulfanyl-Substituted Carboxylic Acid Derivatives via Ireland-Claisen Rearrangements, J. Fluorine Chem. 2014, 167, 84-90
A.-L. Dreier, A. V. Matsnev, J. S. Thrasher, G. Haufe
(Siehe online unter https://doi.org/10.1016/j.jfluchem.2014.05.006) - Pentafluorosulfanyldifluoroacetic acid – rebirth of a promising building-block, Org. Lett. 2014, 16, 2402-2405
A. V. Matsnev, S.-Y. Qing, M. A. Stanton, K. A. Berger, G. Haufe, J. S. Thrasher
(Siehe online unter https://doi.org/10.1021/ol500766v) - Ambiphilic Properties of SF5CF2CF2Br Derived Perfluorinated Radical in Addition Reactions Across Carbon-Carbon Double Bonds, Org. Lett. 2015, 17, 1078-1081
P. Dudzinski, A. Matsnev, J. S. Thrasher, G. Haufe
(Siehe online unter https://doi.org/10.1021/acs.orglett.5b00268) - Anti-selective Aldol Reactions of SF5-Acetic Acid Esters with Aldehydes Mediated by Dicyclohexylchloroborane, Org. Lett. 2016, 18, 1012-1015
F. W. Friese, A.-L. Dreier, A. V. Matsnev, C.-G. Daniliuc, J. S. Thrasher, G. Haufe
(Siehe online unter https://doi.org/10.1021/acs.orglett.6b00136) - Synthesis of SF5CF2 containing building blocks and on the instability of this group in specific chemical environments and reaction conditions, J. Org. Chem. 2016, 81, 4454-4463
P. Dudzinski, A. V. Matsnev, J. S. Thrasher, G. Haufe
(Siehe online unter https://doi.org/10.1021/acs.joc.6b00550) - The Ireland-Claisen rearrangement as a useful tool for the synthesis of new α-(pentafluorosulfanyl)- and α-(trifluoromethyl)-substituted carboxylic acid derivatives. J. Org. Chem. 2017, 82, 1638-1648
A.-L. Dreier, B. Beutel, C. Mück-Lichtenfeld, A. V. Matsnev, J. S. Thrasher, G. Haufe
(Siehe online unter https://doi.org/10.1021/acs.joc.6b02805) - Syn-selective silicon Mukaiyamatype aldol reactions of (pentafluoro-λ6-sulfanyl)acetic acid esters with aldehydes, Beilstein J. Org. Chem. 2018, 14, 373–380
A.-L. Dreier, A. V. Matsnev, J. S. Thrasher, G. Haufe
(Siehe online unter https://doi.org/10.3762/bjoc.14.25)
