Jenseits von Friedel und Crafts: dirigierte Alkylierung von C‐H‐Bindungen in Arenen

Abstract

Die Alkylierung von Arenen ist eine der grundlegendsten Transformationen in der chemischen Synthese und führt in vielen wissenschaftlichen Bereichen zu privilegierten Molekülgerüsten. Klassische Methoden für die Einführung von Alkylgruppen in Arene beruhen zumeist auf der Friedel‐Crafts‐Reaktion, Radikaladditionen, Metallierungen oder Präfunktionalisierungen von Arenen; die Anwendungsbreite, Effizienz und Selektivität dieser Methoden sind jedoch begrenzt. Außerdem bauen sie auf der inhärenten Reaktivität des Ausgangsarens auf, die die Alkylierung in einer bestimmten Position bevorzugt und die Einführung von Alkylketten an anderen Stellen wesentlich schwieriger macht. Dieses Problem kann durch die Verwendung einer dirigierenden Gruppe angegangen werden, die in Gegenwart eines Metallkatalysators die regioselektive Alkylierung einer C‐H‐Bindung vereinfacht. Diese dirigierten Alkylierungen von C‐H‐Bindungen in Arenen werden im vorliegenden Aufsatz zusammengefasst.

Beyond Friedel and Crafts: Directed Alkylation of C−H Bonds in Arenes

“…One of the main limitations of the direct alkylation of CÀHb onds based on the innate reactivity of arenes actually lies in this innate reactivity itself,since one should be able to functionalize positions other than the one dictated by the substrate.D irecting groups, [4] ideally transient ones, [200] still represent an attractive option to achieve this." Shapeselective" catalysis [201] is another attractive concept that has been extensively investigated in petrochemistry but too scarcely in synthetic chemistry,despite its clear potential.…”

“…[4] In addition to these two strategies,the direct alkylation of simple arenes which do not possess any directing group or heteroatom to control the regioselectivity of the transformation is especially challenging and has great potential. [4] In addition to these two strategies,the direct alkylation of simple arenes which do not possess any directing group or heteroatom to control the regioselectivity of the transformation is especially challenging and has great potential.…”

“…[194] Theo xidative dearomatization step proceeds by oxidation of the starting catechol monoether with Pb(OAc) 4 in the presence of potassium carbonate and pinacol, which were used to quench the in situ formed acetic acid and consume the leftover lead(IV) acetate,respectively. [194] Theo xidative dearomatization step proceeds by oxidation of the starting catechol monoether with Pb(OAc) 4 in the presence of potassium carbonate and pinacol, which were used to quench the in situ formed acetic acid and consume the leftover lead(IV) acetate,respectively.…”

“…[3] Forsuch reactions to be of any synthetic value,asingle C(sp 2 ) À Hb ond must be alkylated among all the C À Hb onds present in the starting arene.Asalready extensively discussed in aseparate review, [4] the main strategy exploited to achieve the selective activation of as ingle C(sp 2 )ÀHb ond relies on the use of directing groups.Inthese cases,coordination of the directing group to the metal-based catalyst is crucial to bring the catalyst in proximity to the C(sp 2 ) À Hb ond to activate and, therefore,t oe nsure high levels of reactivity and regioselectivity. [3] Forsuch reactions to be of any synthetic value,asingle C(sp 2 ) À Hb ond must be alkylated among all the C À Hb onds present in the starting arene.Asalready extensively discussed in aseparate review, [4] the main strategy exploited to achieve the selective activation of as ingle C(sp 2 )ÀHb ond relies on the use of directing groups.Inthese cases,coordination of the directing group to the metal-based catalyst is crucial to bring the catalyst in proximity to the C(sp 2 ) À Hb ond to activate and, therefore,t oe nsure high levels of reactivity and regioselectivity.…”

“…Although the concept itself is far from being novel, the direct (metal-catalyzed in most cases) functionalization of C À Hb onds has indeed clearly become,d uring the last 20 years or so,astrategy of prime importance for the selective formation of carbon-carbon bonds.T his led to the development of remarkably efficient processes enabling the direct and selective introduction-sometimes with an almost surgical precision-of various alkyl groups onto aromatic structures. [3] Forsuch reactions to be of any synthetic value,asingle C(sp 2 ) À Hb ond must be alkylated among all the C À Hb onds present in the starting arene.Asalready extensively discussed in aseparate review, [4] the main strategy exploited to achieve the selective activation of as ingle C(sp 2 )ÀHb ond relies on the use of directing groups.Inthese cases,coordination of the directing group to the metal-based catalyst is crucial to bring the catalyst in proximity to the C(sp 2 ) À Hb ond to activate and, therefore,t oe nsure high levels of reactivity and regioselectivity. [5,6] While most directing groups allow the alkylation of the ortho-CÀH bond, some efficient processes have also been reported for the meta-a nd para-alkylation of arenes,a lthough they are still rare.…”