Over the last decade, substantial research has led to the introduction of an impressive number of efficient procedures which allow the selective construction of CC bonds by directly connecting two different CH bonds under oxidative conditions. Common to these methodologies is the generation of the reactive intermediates in situ by activation of both CH bonds. This strategy was introduced by the group of Li as cross-dehydrogenative coupling (CDC) and discloses waste-minimized synthetic alternatives to classic coupling procedures which rely on the use of prefunctionalized starting materials. This Review highlights the recent progress in the field of cross-dehydrogenative C sp 3C formations and provides a comprehensive overview on existing procedures and employed methodologies.

The Cross-Dehydrogenative Coupling of C sp 3H Bonds: A Versatile Strategy for CC Bond Formations

Catalytic Enantioselective Formation of C−C Bonds by Addition to Imines and Hydrazones: A Ten-Year Update

The area of direct asymmetric functionalization of inert C–H bonds has attracted considerable attention in recent years. To realize this type of challenging but promising transformations, a lot of strategies have emerged including asymmetric C–H bond insertion by metal carbenoids or analogs, cross dehydrogenative coupling, [1,5]-hydride transfer, C–H bond functionalization involving a transient metal–carbon species and other miscellaneous methods. This review is intended to summarize and discuss the most recent developments (contributions mainly after 2009) within this area.

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Recent development of direct asymmetric functionalization of inert C–H bonds

Recent advances in synthetic methods for the direct α-functionalization of saturated cyclic amines are described. Methods are categorized according to the in situ formed reactive intermediate (α-amino cation, α-amino anion, and α-amino radical). Transition-metal-catalyzed reactions involving other intermediates have been treated as a separate and fourth class.

Direct α-functionalization of saturated cyclic amines.

In den vergangenen zehn Jahren wurde eine beeindruckende Zahl an Verfahren entwickelt, die den selektiven Aufbau von C-C-Bindungen uber die direkte Verknupfung von zwei unterschiedlichen C-H-Bindungen unter oxidativen Bedingungen ermoglichen. Diesen Methoden ist gemeinsam, dass die reaktiven Zwischenstufen durch Aktivierung der beiden C-H-Bindungen in situ gebildet werden. Diese Strategie wurde von der Gruppe von Li als dehydrierende Kreuzkupplung (CDC, “cross-dehydrogenative coupling”) eingefuhrt und eroffnet abfallarme Synthesealternativen zu klassischen Kupplungsverfahren, die sich auf die Verwendung von vorfunktionalisierten Ausgangsstoffen stutzen. Dieser Aufsatz hebt die Fortschritte auf dem Gebiet der dehydrierenden C sp 3-C-Bindungsknupfungen hervor und liefert einen umfassenden Uberblick uber die vorhandenen Verfahren.

Dehydrierende Kreuzkupplungen von C sp 3‐H‐Bindungen: vielseitige Verfahren zur Bildung von C‐C‐Bindungen

Detailed mechanistic studies on our recently reported asymmetric addition reactions of malonates to dihydroisoquinolines (DHIQs) catalyzed by chiral Pd(II) complexes were carried out. It was found that an N,O-acetal was generated in situ by the reaction of DHIQ with (Boc)2O, and cooperative action of the Pd(II) complex as an acid−base catalyst allowed the formation of a chiral Pd enolate and a reactive iminium ion via α-fragmentation. The iminium ion was also accessible via oxidation with DDQ as an oxidant, and a catalytic asymmetric oxidative Mannich-type reaction was achieved with tetrahydroisoquinolines (THIQs) as starting materials. This oxidation protocol was applicable to N-acryloyl-protected THIQs, allowing the efficient synthesis of optically active tetrahydrobenzo[a]quinolizidine derivatives via intramolecular Michael reaction.

Mechanistic Studies on the Catalytic Asymmetric Mannich-Type Reaction with Dihydroisoquinolines and Development of Oxidative Mannich-Type Reactions Starting from Tetrahydroisoquinolines

Thomas M. Seidel

Papers

Mechanistic Studies on the Catalytic Asymmetric Mannich-Type Reaction with Dihydroisoquinolines and Development of Oxidative Mannich-Type Reactions Starting from Tetrahydroisoquinolines