Publications

2017
Zackaria Nairoukh, Gunda G. K. S. Narayana Kumar, Yury Minko, and Ilan Marek. 2017. “Enantioselective Allylic Alkylation of Stereodefined Polysubstituted Copper Enolates as an Entry to Acyclic Quaternary Carbon Stereocentres.” Chem. Sci. 2017, 8, 627 – 630. Publisher's Version Abstract
A sequence of regio- and stereoselective carbometalation followed by oxidation of ynamides leads to stereodefined fully substituted enolates that subsequently react with various functionalized allyl bromide reagents to provide the expected products possessing an enantiomerically pure quaternary carbon stereocentre in the α-position to the carbonyl group in excellent yields and enantiomeric ratios after cleavage of the oxazolidinone moiety. Three new bonds are formed in a single-pot operation.
Mario P. Wiesenfeldt, Zackaria Nairoukh, Wei Li, and Frank Glorius. 2017. “Hydrogenation of Fluoroarenes: Direct Access to All-cis-(multi)fluorinated Cycloalkanes.” Science 2017, 357, 908 – 912. Publisher's Version Abstract
Carbon-fluorine bonds are highly polarized, and this effect is magnified when several of them reside on the same face of a saturated ring. However, most existing fluorination methods have difficulty consistently producing this all-cis mutual configuration. Wiesenfeldt et al. used a rhodium catalyst in nonpolar solvent to add hydrogens selectively to just one face of a wide variety of flat fluoroarene rings, pushing all fluorines toward the other face. The reaction also pushed fluorine toward the same face as nitrogen and oxygen in heterocycles such as indole and benzofuran.Science, this issue p. 908All-cis-multifluorinated cycloalkanes exhibit intriguing electronic properties. In particular, they display extremely high dipole moments perpendicular to the aliphatic ring, making them highly desired motifs in material science. Very few such motifs have been prepared, as their syntheses require multistep sequences from diastereoselectively prefunctionalized precursors. Herein we report a synthetic strategy to access these valuable materials via the rhodium–cyclic (alkyl)(amino)carbene (CAAC)–catalyzed hydrogenation of readily available fluorinated arenes in hexane. This route enables the scalable single-step preparation of an abundance of multisubstituted and multifluorinated cycloalkanes, including all-cis-1,2,3,4,5,6-hexafluorocyclohexane as well as cis-configured fluorinated aliphatic heterocycles.
Zackaria Nairoukh, Morgan Cormier, and Ilan Marek. 2017. “Merging C–H and C–C Bond Cleavage in Organic Synthesis.” Nat. Rev. Chem. 2017, 1, 0035. Publisher's Version Abstract
Metal-catalysed functionalization of a carbon–hydrogen bond can occur selectively even in the presence of ostensibly more reactive functional groups. Such conversions have changed our perceptions of organic chemistry because we can now consider a C–H bond as a functional group, the reactions of which are among the most attractive and powerful means to rapidly add complexity. Another versatile tool in organic synthesis is the metal-catalysed selective cleavage of C–C bonds. Applying both expedient methods in a tandem process would give us an ideal approach to synthesizing complex molecular architectures. The challenge lies in ensuring that the reactions do not interfere with each other; the simultaneous control of both C–H and C–C bond activations is the subject of this Review. The reactions that meet this challenge and enable a selective merger of C–H and C–C bond activations in a one-pot process are discussed. Their realization could afford sophisticated molecular fragments that are otherwise difficult to access.