Die übergangsmetallkatalysierte C-Alkylierung von Ketonen und sekundären Alkoholen mit Alkoholen umgeht den Einsatz von metallorganischen oder umweltschädlichen Alkylierungsreagentien über die Borrowing-Hydrogen(BH)- oder Hydrogen-Autotransfer(HA)-Aktivierung der Alkoholsubstrate. Da Wasser als einziges Begleitprodukt entsteht, ist das BH-Verfahren atomökonomisch und umweltfreundlich. Viele homogene und heterogene Übergangsmetallkatalysatoren, Ketone und Alkohole sind in dieser Reaktion einsetzbar, sodass das BH-Verfahren aussichtsreich scheint, die derzeitigen Verfahren zu ersetzen, die herkömmliche Alkylierungsreagentien verwenden. Dieser Kurzaufsatz fasst die Fortschritte in der übergangsmetallkatalysierten α-Alkylierung von Ketonen und β-Alkylierung von sekundären Alkoholen mit Alkoholen mithilfe der BH-Technik während der letzten fünf Jahre zusammen. Auch die Eignung der BH-Strategie zur C-C-Bindungsbildung wird diskutiert.

Transition-metal-catalyzed C-alkylation of ketones and secondary alcohols, with alcohols, avoids use of organometallic or environmentally unfriendly alkylating agents by means of borrowing hydrogen (BH) or hydrogen autotransfer (HA) activation of the alcohol substrates. Water is formed as the only by-product, thus making the BH process atom-economical and environmentally benign. Diverse homogeneous and heterogeneous transition-metal catalysts, ketones, and alcohols can be used for this transformation, thus rendering the BH process promising for replacing those procedures that use traditional alkylating agents. This Minireview summarizes the advances during the last five years in transition-metal-catalyzed BH α-alkylation of ketones, and β-alkylation of secondary alcohols with alcohols. A discussion on the application of the BH strategy for C−C bond formation is included.

The Cu-catalyzed, one-pot tandem (asymmetric) borylation of β-chloroalkyl aryl ketones via the in situ generated acyclic enones with bis(pinacolato)diboron was achieved efficiently to reach up to 97 % yield and 99 % enantioselectivity for the formal sp³ CCl borylation products. The present methodology provides an efficient alternative route to (chiral) alkylboron compounds.

Efficient palladium-catalyzed cross-coupling reactions of the internal olefins α-cyanoketene dithioacetals with a variety of olefins were achieved in dioxane/HOAc/DMSO (9:3:1 v/v/v) under air atmosphere or by means of AgOAc as the terminal oxidant. Electron-deficient terminal olefins reacted to form the linear diene derivatives with air as the oxidant. Styrenes underwent the cross-coupling to give both the linear and branched dienes when using AgOAc as the oxidant. Unactivated cyclic and linear internal olefin substrates both reacted in the presence of a catalytic amount of benzoquinone in air to produce skipped dienes. The typical products were structurally confirmed by X-ray crystallography.

Brønsted acid-mediated annulation of internal olefins α-oxo ketene dithioacetals to pyrroles was efficiently achieved to afford cyclopenta[b]pyrroles. A pair of Brønsted acids with acid strengths, that is, trifluoroacetic acid, and para-toluenesulfonic acid hydrate, were applied to promote the annulation reactions. The resultant products were readily oxidized to sulfones by meta-chloroperoxybenzoic acid. Subsequent treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene gave desulfurized terminal olefins or [2+2] cycloaddition products from the desulfurized olefin intermediates. The present protocol provides facile access to structurally diverse cyclopenta[b]pyrrole derivatives under mild conditions.

The functionalization of internal olefins has been a challenging task in organic synthesis. Efficient Cu^II-catalyzed trifluoromethylation of internal olefins, that is, α-oxoketene dithioacetals, has been achieved by using Cu(OH)₂ as a catalyst and TMSCF₃ as a trifluoromethylating reagent. The push–pull effect from the polarized olefin substrates facilitates the internal olefinic CH trifluoromethylation. Cyclic and acyclic dithioalkyl α-oxoketene acetals were used as the substrates and various substituents were tolerated. The internal olefinic CH bond cleavage was not involved in the rate-determining step, and a mechanism that involves radicals is proposed based on a TEMPO-quenching experiment of the trifluoromethylation reaction. Further derivatization of the resultant CF₃ olefins led to multifunctionalized tetrasubstituted CF₃ olefins and trifluoromethylated N-heterocycles.

Highly efficient arylations of β-chloro ketones and their ester and amide derivatives were achieved by means of domino dehydrochlorination/Rh(I)-catalyzed conjugate addition. In situ generated vinyl ketones and their analogues were identified as the reaction intermediates. The present synthetic protocol provides a concise route to (chiral) β-aryl ketones, esters, and amides.

Die asymmetrische Hydrierung spielt in der organischen Synthese eine wichtige Rolle, aber erst in den letzten drei Jahren wurde die Hydrierung von schwierigen Substraten, wie N-ungeschützten Iminen, Enaminen und N-Heteroarenen (1H-Indole, 1H-Pyrrole, Pyridine, Chinoline und Chinoxaline) vermehrt untersucht. Wenn man die Wechselwirkungen einer Brønsted-Säure mit einer Lewis-Base betrachtet, könnten Brønsted-Säuren als ideale Aktivatoren von CN-Bindungen genutzt werden. Dieser Kurzaufsatz fasst aktuelle Entwicklungen bei der übergangsmetallkatalysierten, Brønsted-Säure-aktivierten asymmetrischen Hydrierung dieser anspruchsvollen Substrate zusammen und präsentiert damit eine vielversprechende Substrataktivierungsstrategie für Umwandlungen unter Beteiligung von CN-Bindungen.

Asymmetric hydrogenation plays an important role in organic synthesis, but that of the challenging substrates such as N-unprotected imines, enamines, and N-heteroaromatic compounds (1H-indoles, 1H-pyrroles, pyridines, quinolines, and quinoxalines) has only received increased attention in the past three years. Considering the interaction modes of a Brønsted acid with a Lewis base, Brønsted acids may be used as the ideal activators of CN bonds. This Minireview summarizes the recent advances in transition-metal-catalyzed, Brønsted acid activated asymmetric hydrogenation of these challenging substrates, thus offering a promising substrate activation strategy for transformations involving CN bonds.

Versatile syntheses of secondary and tertiary amines by highly efficient direct N-alkylation of primary and secondary amines with alcohols or by deaminative self-coupling of primary amines have been successfully realized by means of a heterogeneous bimetallic Pt–Sn/γ-Al₂O₃ catalyst (0.5 wt % Pt, Pt/Sn molar ratio=1:3) through a borrowing-hydrogen strategy. In the presence of oxygen, imines were also efficiently prepared from the tandem reactions of amines with alcohols or between two primary amines. The proposed mechanism reveals that an alcohol or amine substrate is initially dehydrogenated to an aldehyde/ketone or NH-imine with concomitant formation of a [PtSn] hydride. Condensation of the aldehyde/ketone species or deamination of the NH-imine intermediate with another molecule of amine forms an N-substituted imine which is then reduced to a new amine product by the in-situ generated [PtSn] hydride under a nitrogen atmosphere or remains unchanged as the final product under an oxygen atmosphere. The Pt–Sn/γ-Al₂O₃ catalyst can be easily recycled without Pt metal leaching and has exhibited very high catalytic activity toward a wide range of amine and alcohol substrates, which suggests potential for application in the direct production of secondary and tertiary amines and N-substituted imines.

FeCl₃⋅6 H₂O- and FeBr₃-catalyzed Prins cyclization/halogenation of alkynyl aldehyde acetals has been realized with acetyl chloride or bromide as halogen source in dichloromethane to afford 2-(1-halobenzylidene or alkylidene)-substituted five-membered carbo- and heterocycles, and thus provides an alternative route for vinylic CCl and CBr bond formation. Five- to eight-membered cyclic enones were efficiently synthesized by FeCl₃⋅6 H₂O-catalyzed intramolecular cyclization of alkynyl aldehyde acetals in acetone under mild conditions. An oxocarbonium species generated in situ is proposed to initiate the reaction, and the target products are formed via vinylogous carbenium cation and oxete intermediates according to DFT calculations. Intermolecular reactions of alkynes and aldehyde acetals were also investigated with 20–40 mol % FeCl₃⋅6 H₂O catalyst, and produced α,β-unsaturated enones and chlorinated indene derivatives. The present protocol has applications in the synthesis of carbo-, oxa- and azacycles.