Ambient Moisture Accelerates Hydroamination Reactions of Vinylarenes with Alkali‐Metal Amides under Air

Abstract

A straightforward alkali-metal-mediated hydroamination of styrenes using biorenewable 2-methyltetrahydrofuran as a solvent is reported. Refuting the conventional wisdom of the incompatibility of organolithium reagents with air and moisture, shown here is that the presence of moisture is key in favoring formation of the target phenethylamines over competing olefin polymerization products. The method is also compatible with sodium amides, with the latter showing excellent promise as highly efficient catalysts under inert atmosphere conditions. Scheme 1. Comparison of state-of-art catalytic procedures with our airand moisture-compatible stoichiometric protocol.

Aminopotassiation by Mixed Potassium/Lithium Amides: A Synthetic Path to Difficult to Access Phenethylamine Derivates

“…For example, as recently shown by Hevia et al, moisture plays a significant role in hydroamination reactions. [14] Furthermore, a source from which the metalated 4-methoxystyrene abstracts a proton could not be identified. [15] To prove this reaction, also the intermediate of the aminometalation reaction with a potassium amide should be isolated.…”

Hydroalkylation of Styrenes with Benzylamines by Potassium Hydride

“…Based on the previous reports which revealed that potassium amides possess dimeric (or oligomeric) structures in THF solution, [40–42] we adopted a dimeric structure as a model complex of the potassium amide. In addition, given that use of more than two equivalents of benzylamine ( 4 ) to KH was required to avoid the undesired side reactions ( Scheme 8), we assumed that the coordination of benzylamine ( 4 ) should be involved in the potassium amide [18,24] . We thus located the potassium amide dimer INT 1‐ N having the coordination of benzylamine ( 4 ) and THF ( Scheme 11).…”

“…Despite these advances, engagement of benzylamines in their deprotonative benzylic alkylation with styrenes remains elusive. When primary and secondary amines are employed, the base‐mediated deprotonation occurs on the amine site and the resulting amide anions show the propensity to undergo hydroamination [20–24] . Interestingly, Hultzsch observed that the reaction of benzylamine ( 4 ) and styrene ( 5 ) catalyzed by KN(SiMe 3 ) 2 and TMEDA affords not only hydroamination products 6 and 6′ , but also 1,3‐diphenylpropylamine ( 7 ) as a minor co‐product through hydroalkylation of styrene ( 5 ) ( Scheme 3).…”

Aminometallierung mit einem gemischten K/Li‐Amid: Eine Syntheseroute zu schwer zugänglichen Phenethylamin‐Derivaten

“…Leider führte der Wegfall einer zweiten stabilisierenden Phenylgruppe zu einer komplizierteren Reaktionskinetik, die empfindlicher auf ¾nderungen der Reaktionsparameter reagierte und dadurch das Abfangen mit Elektrophilen erschwerte. [14] Zudem konnte die Quelle, von der das metallierte 4-Methoxystyrol ein Proton abstrahiert, nicht identifiziert werden. [15] Um diese Reaktion zu untersuchen, sollte auch hier das Zwischenprodukt der Aminometallierungsreaktion mit einem Kaliumamid isoliert werden.…”