Negishi Cross-Couplings of Unsaturated Halides Bearing Relatively Acidic Hydrogen Atoms with Organozinc Reagents

Abstract

A wide range of polyfunctional aryl, heteroaryl, alkyl, and benzylic zinc reagents were coupled with unsaturated halides bearing an acidic NH or OH function, using Pd(OAc)(2) (1 mol %) and S-Phos (2 mol %) as catalyst without the need of protecting groups.

Regio‐ und chemoselektive Metallierung von Arenen und Heteroarenen mit gehinderten Metallamidbasen

“…Diese Toleranz gegenüber OH-und NH-Gruppen wurde besonders ausführlich in Bezug auf Organozinkreagentien untersucht. [53,54] Folglich ermçg-licht ein adäquates Pd-Katalysatorsystem vielfältige Kreuzkupplungen der Organozinkverbindungen 34-36 mit Arylbromiden oder -iodiden, die NH 2 -, RNH-Gruppen bzw. eine sekundäre Alkoholfunktion tragen.…”

“…eine sekundäre Alkoholfunktion tragen. [52,53] Das Zinkreagens 36 wird vorzugsweise über 90 min zu einem Gemisch aus sekundärem Alkohol und dem Katalysatorsystem zugegeben (Schema 9).…”

Direct B‐Alkyl Suzuki–Miyaura Cross‐Coupling of Trialkyl‐ boranes with Aryl Bromides in the Presence of Unmasked Acidic or Basic Functions and Base‐Labile Protections under Mild Non‐Aqueous Conditions

“…[14] Besides, basic functions such as amines might interfere with transition metal catalysis. [15] In view of the fact that these functions are the cornerstones of combinatorial chemistry, sparing the two-step detour of protection and deprotection would be highly beneficial to both academia and industry. Indeed, considering the protolysis of trialkylboranes by carboxylic acids [16] or phenols, [17] and the strong coordination of amines with boranes or boronic acids, [18] this type of direct coupling is non-trivial.…”

“…[22] Recently, Knochels group accomplished Negishi coupling for substrates with relatively acidic OH and NH groups. [15] Herein we report our results for the direct Suzuki cross-alkylation of aryl bromides bearing unmasked acidic or basic functions as well as common polar functional groups.…”

Negishi Cross‐Couplings Compatible with Unprotected Amide Functions

“…[5] Herein, we report reaction conditions that are compatible with the amide function (Scheme 1). This functional group is ubiquitous in pharmaceutically active compounds and its tolerance in cross-coupling reactions is therefore especially important.…”