a-two-step-protocol-for-umpolung-functionalization-ketones-via

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. ...

Ariel University

Enolonium species/iodo(III)enolates of carbonyl compounds have been suggested to be intermediates in a wide variety of hypervalent iodine induced chemical transformations of ketones, including α-C-O, α-C-N, α-C-C, and α-carbon-halide bond formation, but they have never been characterized. We report that these elusive umpoled enolates may be made as discrete species that are stable for several minutes at -78 °C, and report the first spectroscopic identification of such species. It is shown that enolonium species are direct intermediates in C-O, C-N, C-Cl, and C-C bond forming reactions. Our results open up chemical space for designing a variety of new transformations. We showcase the ability of enolonium species to react with prenyl, crotyl, cinnamyl, and allyl silanes with absolute regioselectivity in up to 92 % yield.

Enolonium Species-Umpoled Enolates.

Herein it is shown, for the first time, that enolonium species are powerful electrophiles capable of reacting with aromatic compounds in an intermolecular manner to afford α-arylated ketones. The reaction is compatible with a variety of functional groups, is of wide scope with respect to aromatic compounds and ketone, and even works for polymerization-prone substrates such as substituted pyrroles, thiophenes, and furans. Only 1.6 to 5 equiv of the commodity aromatic substrates is needed.

Transition-Metal-Free Intermolecular α-Arylation of Ketones via Enolonium Species.

Enolonium species, resulting from the umpolung of ketone enolates by Koser's hypervalent iodine reagents activated by boron trifluoride, react with a variety of nitrogen heterocycles to form α-aminated ketones. The reactions are mild and complete in 4-5 h. Additionally, α-azidation of the enolonium species takes place using trimethylsilyl azide as a convenient source of azide nucleophile.

α-N-Heteroarylation and α-Azidation of Ketones via Enolonium Species.

Due to their closely matched reactivity, the coupling of two dissimilar ketone enolates to form a 1,4-diketone remains a challenge in organic synthesis. We herein report that umpolung of a ketone trimethylsilyl enol ether (1 equiv) to form a discrete enolonium species, followed by addition of as little as 1.2-1.4 equivalents of a second trimethylsilyl enol ether, provides an attractive solution to this problem. A wide array of enolates may be used to form the 1,4-diketone products in 38 to 74% yield. Due to the use of two TMS enol ethers as precursors, an optimization of the cross-coupling should include investigating the order of addition.

Article	Year
Enolonium Species-Umpoled Enolates. Angewandte Chemie (International ed. in English)\| PubMed ID: 28128488	2017
Transition-Metal-Free Intermolecular α-Arylation of Ketones via Enolonium Species. Organic letters\| PubMed ID: 29140710	2017
α-N-Heteroarylation and α-Azidation of Ketones via Enolonium Species. The Journal of organic chemistry\| PubMed ID: 29334466	2018
Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones. Beilstein journal of organic chemistry\| PubMed ID: 29977370	2018

Shimon Maksymenko

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