Modern Transition-Metal-Catalyzed Carbon–Halogen Bond Formation

Abstract

The high utility of halogenated organic compounds has prompted the development of a vast number of transformations which install the carbon-halogen motif. Traditional routes to these building blocks have commonly involved multiple steps, harsh reaction conditions, and the use of stoichiometric and/or toxic reagents. In this regard, using transition metals to catalyze the synthesis of organohalides has become a mature field in itself, and applying these technologies has allowed for a decrease in the production of waste, higher levels of regio- and stereoselectivity, and the ability to produce enantioenriched target compounds. Furthermore, transition metals offer the distinct advantage of possessing a diverse spectrum of mechanistic possibilities which translate to the capability to apply new substrate classes and afford novel and difficult-to-access structures. This Review provides comprehensive coverage of modern transition metal-catalyzed syntheses of organohalides via a diverse array of mechanisms. Attention is given to the seminal stoichiometric organometallic studies which led to the corresponding catalytic processes being realized. By breaking this field down into the synthesis of aryl, vinyl, and alkyl halides, it becomes clear which methods have surfaced as most favored for each individual class. In general, a pronounced shift toward the use of C-H bonds as key functional groups, in addition to methods which proceed by catalytic, radical-based mechanisms has occurred. Although always evolving, this field appears to be heading in the direction of using starting materials with a significantly lower degree of prefunctionalization in addition to less expensive and abundant metal catalysts.

Pd-Catalyzed Decarbonylative Cross-Couplings of Aroyl Chlorides

“…As shown in Figure 1, our proposed Pd-catalyzed decarbonylative cross-coupling from aroyl chlorides leverages C–Cl bond-forming reductive elimination from Pd II as a key step. 11–13 The resulting aryl chloride products then engage in situ with the same Pd catalyst to form C–C, C–N, C–O, C–S, C–B, and C–CF 3 bonds.…”

“…16,17 The requirement for extremely high temperatures likely reflects kinetic challenges associated with the decarbonylation 14 and/or C–Cl coupling steps of the cycle. 11–13 …”

Palladium‐katalysierte intermolekulare Aryliodierung von internen Alkinen

“…Lautens und Mitarbeiter legten den Grundstein in diesem Gebiet durch die Entwicklung mehrerer Carboiodierungsreaktionen von Mehrfachbindungen. [20] Hier berichten wir über eine Pd-katalysierte,i ntermolekulare Reaktion zwischen einer großen Vielzahl an Aryliodiden mit internen Alkinen, um stereoselektiv den Zugang zu Alkenyliodiden zu erhalten. [12] Eine bemerkenswerte Ausnahme hierfür wurde während des Erstellens dieses Manuskriptes berichtet, die eine nicht-stereoselektive Ni-katalysierte Alkin-Aryliodierungsreaktion, welche eine radikalische Zwischenstufe beinhaltet, beschreibt.…”

“…Eine Vielzahl anderer Liganden, einschließlich Xantphos-Derivaten, führte zu geringem Umsatz. [20] Eine seltene Ausnahme ist das Ergebnis, über welches Arndtsen und Mitarbeiter berichteten. Wirv ermuten, dass der Schlüssel fürd ie reduktive Eliminierung in der Verwen-dung eines Überschusses an Liganden besteht, der beides, elektronenarm und zweizähnig ist.…”

Site‐Selective Remote Radical C−H Functionalization of Unactivated C−H Bonds in Amides Using Sulfone Reagents

“…[13] We found that chlorination could be realized by using the commercial trifluoromethanesulfonyl chloride as the chloride source under slightly modified reaction conditions (5a-c). Selective halogenation of unactivated CÀHb onds is an important transformation.…”