Coordinating Sulfonyl Substrates in Metal-Catalyzed Reactions

Abstract

Metal-coordinating heteroaryl sulfonyl groups, such as the 2-pyridylsulfonyl and the 8-quinolylsulfonyl group, allow the control of the reactivity and stereoselectivity of a great variety of metal-mediated reactions. This concept is rather general and has been applied for the activation of vinyl sulfones and N-sulfonyl imines, as well as in the direct C H functionalization of N-H heterocycles. In particular, this kind of coordinating group has played a key role in the enantioselective Rh-catalyzed addition of boronic acids and Cu-catalyzed reduction of 2-pyridyl vinyl sulfones, the Cu-catalyzed addition of organozinc reagents, and the direct Mannich reaction of glycinate imines to N-heteroarylsulfonyl imines. In addition, a general procedure for the Pd-catalyzed C-2 alkenylation of N-(2-pyridylsulfonyl)indoles and pyrroles has been developed.

Sulfone–Metal Exchange and Alkylation of Sulfonylnitriles

“…Unlike most alkenenitriles , [23] 18 engaged in afacile conjugate addition upon addition of PhLi. Theefficacy of the conjugate addition likely stems from chelation with the sulfone [12] and pyridine, [14] promoting conjugate addition via the six-membered complex 19.T he resultant lithiated nitrile was efficiently trapped with methyl iodide to afford the sulfonyl nitrile 15 j,ab,b-disubstituted nitrile.S tandard sulfonemagnesium exchange of 15 j and subsequent methylation afforded the quaternary nitrile 4q (82 %yield).…”

“…[8] Conceptually,as ulfone-metal exchange would combine the exceptionally rich chemistry of sulfones [9] with the diverse alkylation potential of organometallics while providing aversatile alternative to reductive desulfonylation. [2] Developing as ulfone-metal exchange requires overcoming the excellent directing group ability of sulfones, [12] and guiding organometallics to attack at the tetrasubstituted sulfur center (12)r ather than complex-directed ortho deprotonation [13] (11). The sequence obviates the need for two equivalents of as trong base,w hich is typically required in nitrile alkylations.…”

“…[22] In contrast, as ulfone-magnesium exchange with 15 i triggered af acile 5-exo-tet cyclization to afford the cyclopentylcarbonitrile 4p (entry 15). Theefficacy of the conjugate addition likely stems from chelation with the sulfone [12] and pyridine, [14] promoting conjugate addition via the six-membered complex 19.T he resultant lithiated nitrile was efficiently trapped with methyl iodide to afford the sulfonyl nitrile 15 j,ab,b-disubstituted nitrile.S tandard sulfonemagnesium exchange of 15 j and subsequent methylation afforded the quaternary nitrile 4q (82 %yield). Condensing pyridylsulfonylacetonitrile (14)with benzaldehyde afforded the alkenesulfonylnitrile 18.…”

“…The sequence obviates the need for two equivalents of as trong base,w hich is typically required in nitrile alkylations. [2] Developing as ulfone-metal exchange requires overcoming the excellent directing group ability of sulfones, [12] and guiding organometallics to attack at the tetrasubstituted sulfur center (12)r ather than complex-directed ortho deprotonation [13] (11). Indeed, attempted sulfone-metal exchange with BuLi and the phenylsulfone 10 afforded the imine 13,p resumably by complexation, ortho-deprotonation (11), and attack of the resultant aryllithium on the nitrile.…”

Cyanoalkylierung: Alkylnitrile in katalytischen C‐C‐Kupplungen

“…Erst vor kurzem beschrieben Nakamura und Mitarbeiter eine hoch enantioselektive decarboxylierende Mannich-Reaktion von Cyanoessigsäure mithilfe des chiralen Palladiumkomplexes 26,b ei der die entsprechenden b-Aminonitrile in guten Ausbeuten und mit mäßigen bis guten Enantiomerenüberschüssen gebildet wurden (Schema 29). [49] [50] Bisher wurde nur ein Beispiel für die metallfreie asymmetrische decarboxylierende Cyanomethylierung beschrieben. Der in Schema 30 gezeigte,v on l-Prolin abgeleitete difunktionelle Thioharnstoff fçrdert die Reaktion von Cyanoessigsäure mit unterschiedlich substituierten Isatinen unter Bildung enantiomerenangereicherter substituierter 3-Hydroxyindole in guten Ausbeuten nach langen Reaktionszeiten.…”