Asymmetric Nickel-Catalyzed Negishi Cross-Couplings of Secondary α-Bromo Amides with Organozinc Reagents

Fischer, Christian; Fu, Gregory C.

doi:10.1021/ja0506509

Cited by 316 publications

(128 citation statements)

References 6 publications

(8 reference statements)

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…Die durch NiCl 2 und iPr-Pybox katalysierten Umsetzungen von racemischen a-Bromamiden führten mit guten Ausbeuten und hohen Enantiomerenüber-schüssen (ee) zu zahlreichen funktionalisierten a-substituierten Amiden (Schema 3). [11] Die Reaktionen erfordern keinerlei besondere Vorkehrungen und laufen an der Luft ab. An diesen Kupplungen nehmen sowohl nichtfunktionalisierte als auch funktionalisierte Organozinkreagentien teil, einschließlich jener mit Olefin-, Benzylether-, Acetal-, Imid-und Nitrileinheiten.…”

Section: Nickelkatalysierte Reaktionenunclassified

Sekundäre Alkylhalogenide in übergangsmetallkatalysierten Kreuzkupplungen

2009

View full text Add to dashboard Cite

Sekundär, aber nicht zweitrangig: In den vergangenen fünf Jahren hat die Verwendung von sekundären Alkylhalogeniden in übergangsmetallkatalysierten Kreuzkupplungen erheblich zugenommen. Hier werden ausgewählte Beispiele für solche Prozesse unter Berücksichtigung von mechanistischen und stereochemischen Aspekten betrachtet.magnified imageEs wurde viel Kraft in die Entwicklung von metallkatalysierten Kreuzkupplungen mit Alkylhalogeniden als elektrophile Reaktionspartner investiert. Während schon heute zahlreiche primäre Alkylhalogenide wirksam in Kreuzkupplungen verwendet werden können, stehen Umsetzungen mit sekundären Alkylhalogeniden gerade erst am Anfang. Hier werden ausgewählte Kreuzkupplungen vorgestellt, in denen sekundäre Alkylhalogenide als Elektrophile wirken. Dabei wird den verwendeten Übergangsmetallen, den Reaktionsmechanismen und dem stereochemischen Verlauf besondere Beachtung geschenkt.

show abstract

Section: Nickelkatalysierte Reaktionenunclassified

Sekundäre Alkylhalogenide in übergangsmetallkatalysierten Kreuzkupplungen

2009

View full text Add to dashboard Cite

show abstract

“…The reaction conditions were optimized carefully, and it was found that the optimal combination of a solvent, nickel precursor, and additive differed for each class of substrate. [6] Interestingly, in each of these studies, nickel-pybox complexes formed in situ were found to be the most active and most selective catalysts; furthermore, donor solvents, such as 1,3-dimethyl-2-imidazolidinone (DMI), N,N-dimethylacetamide (DMA), and N,Ndimethylformamide (DMF), were found to be crucial. The exact mechanism of these transformations still remains to be elucidated.…”

mentioning

confidence: 97%

“…Thus, the rate of reductive elimination is increased relative to that of undesired b-hydride elimination. Recently, Fu and co-workers developed a number of impressive highly enantioselective nickelcatalyzed Negishi, [6] Hiyama, [7] and Suzuki-Miyaura [8] crosscoupling reactions of secondary alkyl halides. The last of these methods is the only asymmetric cross-coupling described to date in which non-activated secondary alkyl halides can be used and thus paves the way for exciting future developments.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Asymmetric Cross‐Coupling of Non‐Activated Secondary Alkyl Halides

Glorius¹

2008

Angew Chem Int Ed

145

View full text Add to dashboard Cite

asymmetric catalysis · cross-coupling · Negishi coupling · nickel · Suzuki-Miyaura couplingModern transition-metal-catalyzed cross-coupling reactions have altered organic synthesis enormously, [1] and the coupling of aryl and alkenyl electrophiles has become a routine transformation in natural product and fine-chemical synthesis. For a long time, equivalent reactions of alkyl electrophiles, especially those with non-activated b hydrogen atoms, remained elusive. The difficulties encountered in attempts to carry out such reactions have been ascribed to a slow oxidative-addition step and undesired side reactions, such as b-hydride elimination. Palladium complexes of electron-rich phosphines, in particular P(c-Hex) 3 and PtBu 2 Me, were eventually found to be competent catalysts for the Suzuki-Miyaura coupling and related reactions of primary alkyl halides under mild conditions. [2,3] Even more desirable and challenging is the coupling of secondary alkyl halides: challenging, as the increased steric demand and electron richness of these substrates leads to a reduced rate of oxidative addition; desirable, as a new stereogenic center is often formed. Whereas palladiumcatalyzed methods are limited to primary alkyl halide substrates, cheaper nickel complexes were found to be uniquely suited to the catalysis of the cross-coupling of secondary alkyl halides. [4,5] Bi-and tridentate nitrogen ligands (Scheme 1), many of which are commercially available, were found to be key to success of these nickel-catalyzed reactions. These chelate ligands favor the cis orientation of the coupling partners at the nickel center. Thus, the rate of reductive elimination is increased relative to that of undesired b-hydride elimination. Recently, Fu and co-workers developed a number of impressive highly enantioselective nickelcatalyzed Negishi, [6] Hiyama, [7] and Suzuki-Miyaura [8] crosscoupling reactions of secondary alkyl halides. The last of these methods is the only asymmetric cross-coupling described to date in which non-activated secondary alkyl halides can be used and thus paves the way for exciting future developments.In 2003, Zhou and Fu reported the high catalytic activity of nickel-pybox complexes formed in situ in the Negishi coupling of non-activated secondary alkyl bromides and iodides with organozinc reagents at ambient temperature. [2,9] Their study served as a starting point for the development of an impressive series of asymmetric Negishi coupling reactions of secondary alkyl halides.[6] Activated racemic alkyl halides, such as a-bromoamides,[6a] benzylic chlorides and bromides, [6b] and allylic chlorides, [6c] were coupled successfully as electrophiles with alkyl zinc reagents with high enantioselectivity (Schemes 2 and 3). The reactions were even carried out below ambient temperature. The reaction conditions were optimized carefully, and it was found that the optimal combination of a solvent, nickel precursor, and additive differed for each class of substrate.[6] Interestingly, in each of these studies, nickel-pybox comp...

show abstract

“…Condensed ring substrates 1 f and 1 g also gave the desired products 2 f and 2 g in high yields and with 96 % ee and 92 % ee, respectively (Table 2, entries 6 and 7). The electronrich substituents on 1 h-1 j underwent the IOM addition and decarboxylation processes to yield the enantiomeric adducts (2 h-2 j) in excellent yields and with ee values in the range 84-93 % ee ( Table 2, entries [8][9][10]. The aliphatic substrate 1 k was also found to be suitable, affording chromanone 2 k in 90 % yield and with 85 % ee (Table 2, entry 11).…”

mentioning

confidence: 98%