Recent Advances in Asymmetric Transformations of Unactivated Alkanes and Cycloalkanes through Direct C—H Functionalization

Abstract

The direct conversion of unactivated alkanes and cycloalkanes into structurally diverse molecules through aliphatic C-H functionalization is a useful process, which has attracted intense interest from academia and industry. Methods to control chemo-and site-selectivity, combined with asymmetric catalysis, provide appealing access to high value-added enantiomer-enriched compounds but are far less developed. This review focuses on recent progress in (i) asymmetric reactions of alkanes or cycloalkanes with prochiral substrates which generate a stereocenter adjacent to the cleaved C(sp 3 )-H bond, and (ii) C(sp 3 )-H enantiodiscriminatory reactions creating a new stereogenic center on the carbon of a cleaved C(sp 3 )-H bond. Elegant strategies are discussed, including (a) metal carbene-induced C-H insertions by chiral rhodium catalysts, (b) metal-oxo-mediated C-H oxidation by biomimetic manganese catalysts, (c) enzyme catalysis by cytochromes P450 variants, and (d) dual catalysis by a photocatalyst and a chiral Lewis acid (CLA) or a chiral phosphoric acid (CPA). These catalytic systems can not only precisely recognize primary, secondary and tertiary C-H bonds at specific positions in alkanes and cycloalkanes, but also support a high level of stereoselectivity in the reactions. It is expected that the advances will stimulate further progress in asymmetric catalysis, synthetic methodology, pharmaceutical development and industrial processes.

Chiral polycyclic benzosultams from photocatalytic diastereo- and enantioselective benzylic C–H functionalization

“…On the basis of these experiments and our previous experience, [42][43][44][45] a plausible reaction mechanism is proposed and is shown in Scheme 4a. The photocatalyst (PC1) is first excited to a triplet state (PC1*) by irradiation.…”

Zero-dimensional organic–inorganic hybrid zinc halide with broadband yellow light emission

“…In the past decade, metal halide perovskites have been widely used in solar cells, light-emitting diodes, sensors and lasers due to their excellent photoelectric properties and facile assembly process. [1][2][3][4][5][6] In addition to the excellent photovoltaic effect in solar cells, metal halide perovskites also have become highly desirable candidates for luminescent materials due to high defect tolerance, adjustable band gap and emission position in the whole visible-light range, and high PLQYs. [7][8][9] As a classical three-dimensional (3D) perovskite, APbX 3 (A = Cs + , CH 3 NH 3 + , CH(NH 2 ) + ) have unique advantages of narrow full width at half-maximum (FWHM), wide color gamut and near-unity PLQY.…”

Selectfluor®-enabled photochemical selective C(sp3)–H(sulfonyl)amidation

“…Inspired by these studies and our previous research on photochemical synthesis, 19,20 we chose to investigate if employing Selectfluor® as a multifunctional reagent would enable the photochemical activation of strong C(sp 3 )–H bonds, further single-electron oxidation and combination with different N -centered nucleophiles. Such a process would allow us to develop a versatile and general platform for C–N bond formation without the requirement for transition metal catalysts or external photosensitizes (Scheme 1b).…”

“…15 Lei et al reported that photochemical Minisci-type C(sp 3 )-H arylation of alcohols and cycloalkanes with heteroarenes are promoted by Selectfluor s via hydrogen atom transfer (HAT) pathways, 16,17 and Chupakhin et al developed a blue lightpromoted C(sp 2 )-H azolation reaction of nonaromatic 2Himidazole 1-oxides mediated by Selectfluor s . 18 Inspired by these studies and our previous research on photochemical synthesis, 19,20 we chose to investigate if employing Selectfluor s as a multifunctional reagent would enable the photochemical activation of strong C(sp 3 )-H bonds, further single-electron oxidation and combination with different N-centered nucleophiles. Such a process would allow us to develop a versatile and general platform for C-N bond formation without the requirement for transition metal catalysts or external photosensitizes (Scheme 1b).…”

“…It was found that benzenesulfonamides containing a methyl (product 3), methoxy (5), trifluoromethoxy (6), fluoro (7), chloro (8) or trifluoromethyl group (9) at the para position, fluoro (10) at the meta position, and methyl (11), chloro (12), bromo (13) or trifluoromethyl (14) at the ortho position were all tolerated, delivering the corresponding products in 64-96% yields. Benzenesulfonamides with two or three substituents on the phenyl moiety (products 15-17), a fused ring (18), a heterocycle (19) and an N-methyl group (20) provided yields of 40-97%. Aliphatic sulfonamides also proved to be good substrates.…”