Polyfunctional Lithium Organometallics for Organic Synthesis

Abstract

Multifunctional organic molecules can be achieved by reacting functionalized organolithium compounds [1] with electrophilic reagents, this fact makes these intermediates of relevant interest in synthetic organic chemistry [2]. Another remarkable fact concerning organolithium compounds, compared with other organometallic compounds is that they can be prepared following a great number of different methodologies [3]: hydrogen±lithium exchange (deprotonation), halogen±lithium exchange, transmetallation reactions, carbon±heteroatom bond cleavage and carbolithiation of multiple carbon±carbon bonds. However, the highly ionic character of the carbon±lithium bond [4] makes these compounds extremely reactive and also unstable, so the synthetic processes should be carried out in some cases under very mild reaction conditions.Regarding the stability of functionalized organolithium compounds, it depends mainly on three factors, the most important one being the compatibility of the functional group with the carbon±lithium bond, so in some cases the functionality should be protected. The hybridization of the carbon atom bonded to the lithium atom is also important, so sp derivatives are more stable than the corresponding sp 2 and these are more stable than the sp 3 ones as it happens to the corresponding carbanions. Finally, the relative position of the functionality and the carbanionic center is also relevant, probably the b-functionalized derivatives being the most unstable species due to the existence of two consecutive carbon atoms with opposite polarities, the b-elimination process to give an olefin is extremely favored. Stabilized organolithium compounds, such as lithium enolate intermediates [5], a-organolithium compounds bearing electron-withdrawing groups (RSO, RSO 2 , CN, NO 2 , etc.) and heteroatoms such as sulfur [6], selenium and phosphorus as well as functionalized aryllithium compounds will not be consider in depth in this chapter due to the limited length of this review.The following study is ordered based on the relative position of the functionality and the carbanionic center, as well as on the hybridization of that center.

Preparation of Di-, Tri-, and Tetra-Substituted Functionalized Ferrocenes via Magnesium Organometallics

“…Strong alkyllithium bases as well as sterically hindered lithium amides provide access to a number of polysubstituted ferrocene derivatives . However, the high reactivity of lithioferrocenes usually precludes the presence of sensitive functional groups . The magnesiation of unsubstituted ferrocene using TMP bases has also been described .…”

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

“…Die aus der Metallierung resultierenden, hoch reaktiven Aryllithiumverbindungen sind im Allgemeinen lediglich bei tiefen Temperaturen stabil und reagieren bereits unter milden Bedingungen mit wichtigen funktionellen Gruppen wie Esteroder ungehinderten Amidfunktionen. [10] Im Rahmen dieses Aufsatzes werden neue chemoselektive Basen behandelt; vorzugsweise LiCl-solubilisierte 2,2,6,6-Tetramethylpiperidyl(TMP)-Metallamide, die nun die Synthese von hoch funktionalisierten (Hetero)Aryl-MetallSpezies mit empfindlichen Ester-, Nitril-, Keto-, Azid-, Nitrooder Aldehydfunktionen ermçglichen. Einige wichtige Aspekte von vorhergehenden Metallierungen unter Verwendung von gehinderten Li-oder Mg-Amiden werden ebenfalls beschrieben.…”

“…[12] Mit Nitril-oder Nitrogruppen sind sie lediglich bei sehr tiefen Temperaturen kompatibel (À80 bis À100 8C), und mit Estern reagieren sie bereits bei À100 8C. [10,13] Demgegenüber sind Arylmagnesiumverbindungen, mit einer eher kovalenten Kohlenstoff-Metall-Bindung, toleranter gegenüber vielfälti-gen organischen Funktionalitäten. Auf sehr tiefe Temperaturen kann bei der Synthese hoch funktionalisierter Aryl-und Heteroarylmagnesiumreagentien verzichtet werden.…”

Scaleable Preparation of Sensitive Functionalized Aromatics and Heteroaromatics via Directed Metalation Using tmpZnCl·LiCl

“…For the performance of such transformations, the use of lithium bases has been carefully investigated, although the functional group tolerance is only modest . In addition to the pioneering work of Snieckus and Beak, a number of new selective bases for achieving regio- and chemoselective metalations have already been reported by Kondo, Uchiyama, Mongin, and Mulvey; especially, mixed -ate bases have found useful applications . Recently, we have shown that magnesium bases such as tmpMgCl·LiCl (tmp = 2,2,6,6-tetramethylpiperidyl) or tmp 2 Mg·2LiCl , proved to be highly active and selective magnesium bases even though highly sensitive functionalities such as an aldehyde or a nitro group are not tolerated with such bases.…”