Organometallic Chemistry Volume 37

A Review of the Recent Literature

By I. Fairlamb, J. Lynam

The Royal Society of Chemistry

Copyright © 2011 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-1-84973-137-9

Contents

Preface Ian J. S. Fairlamb and Jason M. Lynam, v,
Synergistic effects in the activation of small molecules by s-block elements Charles T. O’Hara, 1,
Air-stable chiral primary phosphines: part (i) synthesis, stability and applications Rachel M. Hiney, Arne Ficks, Helge Müller-Bunz, Declan G. Gilheany and Lee J. Higham, 27,
Open-shell organometallics: reactivity at the ligand Wojciech I. Dzik and Bas de Bruin, 46,
Alkali/coinage metals – organolithium, organocuprate chemistry Joanna Haywood and Andrew E. H. Wheatley, 79,
Group 2 (Be-Ba) and Group 12 (Zn-Hg) Robert J. Less, Rebecca L. Melen and Dominic S. Wright, 100,
Organo-transition metal cluster complexes Mark G. Humphrey and Marie P. Cifuentes, 115,
Highlights in low-coordinate group 14 organometallic chemistry Richard A. Layfield, 133,

CHAPTER 1

Synergistic effects in the activation of small molecules by s-block elements

Charles T. O’Hara

DOI: 10.1039/9781849732802-00001

This critical review covers recent developments in the special chemistry which can take place when two different s-block metals are combined within the same organometallic mixture or reagent. It will cover a selection of the most widely researched mixed-metal ‘synergic’ systems, and will be confined to mixed alkali metal/magnesium reagents. An overview of the known structural chemistry of these fascinating systems will be presented along with some of their pertinent, recent uses in synthesis, including, in the activation/cleavage of C-H bonds (i.e., a metallation reaction) or induction of metal-halogen exchange in organic molecules. The chapter begins by providing a brief historical overview of mixed s-block metal chemistry.

1 Introduction

Without a shadow of a doubt, two of the most important classes of chemical reagent in modern day synthesis are organolithium and organomagnesium compounds. Organolithiums (as well as lithium amides), exemplified by the commercially available butyllithiums, continue to intrigue chemists due to their diverse structure and bonding, and most importantly useful reactivity. Likewise, their organomagnesium counterparts (including Grignard reagents) have played a key role in synthesis since their discovery at the beginning of the 20th century. In more recent times it has been realised that by combining an alkali metal reagent with a rather unreactive magnesium one to empirically prepare one organometallic ate complex, new ‘synergic’ chemical properties can be forthcoming, which normally cannot be replicated using either monometallic reagent on their own. In general, these synergic ate reagents can perform their desired chemistry in the presence of many highly sensitive functional groups as the subsequent metallo-intermediates are often multiple orders of magnitude more stable than for example their corresponding lithio-intermediates. As such, they can be used at more ambient temperatures, they are generally more selective and there is a potential for safe, large scale syntheses.

The main focus of this critical review will be the most thoroughly researched subclasses, of mixed s-block reagents to date. Firstly, the recent chemistry of lithium alkyl magnesiates will be covered, followed by that of Knochel’s new turbo-reagents (specifically, the turbo-Grignard iPrMgCl·LiCl, and the turbo-Hauser base TMPMgCl·LiCl). Finally, the recent structural and synthetic chemistry of some non-halide hetero- bimetallic, heteroanionic systems will be reviewed.

2 Historical perspective of bimetallic s-block ates

The first bimetallic ate complex incorporating two s-block metals, Ph3LiMg, was prepared by Wittig in 1951 by directly combining the two homometallic aryl compounds PhLi and Ph2Mg. Even at its conception, special synergic properties of this reagent were realised – although not explicitly stated as such – by Wittig when he discovered that upon reaction with benzalaceto- phenone, a 1,4-addition product was forthcoming with LiMgPh3, whereas in contrast with LiPh a 1,2-addition was observed (Scheme 1).

Wittig also showed how ate complexes function as bases towards diphenylmethane; however, development of ates as widely utilised and effective reagents in synthesis did not progress to a great extent until the 21st century. In keeping with most of the early advances in the area, Wittig’s ate complex was homoleptic in nature. Over the next 15 years, several advances in ate chemistry were forthcoming culminating in the publication of the first review of this area by Tochtermann. In his 1993 seminal review, Weiss outlined the importance of solid state structural determination as a tool to indentify “the true nature of these (ate) compounds”, and discusses the structures of several organolithiates, organoberyllates and organomagnesates. More recently several reviews on new ate systems have been published which focus predominantly on heteroleptic systems. In this selective review, the recent chemistry (both structural and synthetic) of several widely researched and high interest complexes will be overviewed.

3 Chemistry of alkyl lithium magnesiates

3.1 Synthesis of alkyl lithium magnesiates

In this section a series of homoleptic lithium tri- and tetra-alkyl (also aryl or allyl) magnesiate reagents will be discussed. These are sometimes referred to as lower- and higher-order magnesiates respectively. They are generally prepared by one of two methods: (a) treating the respective alkyllithium and dialkylmagnesium reagents in a 1:1 or 2:1 ratio respectively; or, (b) by combining three or four molar equivalents of an alkyllithium with one equivalent of a magnesium halide (Scheme 2). A third more specific route which can be employed in the synthesis of lithium magnesiates (specifically LiMgsBu3 or in the unusual stoichiometric example Li3MgsBu5) is the reduction of sBu2Mg with lithium metal (Scheme 2). As alluded to earlier, the synthetic chemistry of this class of reagent was not widely utilised until recently, although there are some early reports in the literature. A detailed look at more modern synthetic applications will be taken in Section 3.3.

3.2 Structural chemistry of alkyl lithium magnesiates

From a structural perspective, it is perhaps surprising that the reports of only seven lithium magnesiates containing solely alkyl, alkynyl or aryl anions have been deposited with the Cambridge Crystallographic Database. Six of these structures (Fig. 1) were published early by Weiss and co-workers and they all contain TMEDA (N, N, N’, N’-tetramethylethylenediamine) as a donor solvent which in the majority of cases solvates the Li centres. The only alkyl examples amongst these are the tetramethyl species [(TMEDA)·Li(µ-Me)2Mg(µ-Me)2Li·(TMEDA)] and the benzyl-incorporated solvent-separated ion pair [Li·(TMEDA)2]+ [(TMEDA)-Li(µ-benzyl)2Mg(benzyl)2]-. When the alkynyl ligand PhC[equivalent to]C- is utilised two different lithium magnesiates were formed. The first of which closely resembles the structural motif adopted by the aforementioned Me complex; whilst the second is a dimer of [(TMEDA)Mg(C[equivalent to]CPh)3Li] units. An unusual feature of this latter molecule is that TMEDA coordinates to Mg rather than Li. This renders the Mg centre five-coordinate, with the ligands adopting a trigonal bipyramidal arrangement around the group 2 metal. This motif resembles that of Mulvey’s much later reported ‘inverse crown’ complexes. Two phenyl-containing lithium magnesiates are known. Both have the same metal-anion constitution (i.e., Li2Mg2Ph6); however, one adopts a contacted ion pair structure, whereby the Li centres are bound to one TMEDA molecule each, whilst the other is solvent separated and each Li is bound to two TMEDA molecules (Fig. 1). Power and Waggoner have shown that by incorporating the bulky aryl substituent 2,4,6-iPrC6H2 within a lithium magnesiate, a binuclear tris(aryl) complex is formed (Fig. 1).

3.3 Synthetic utilisation of alkyl lithium magnesiates

Turning to the synthetic utilisation of lithium alkyl magnesiates, they are traditionally employed in three main types of reaction, namely deprotonation, nucleophilic addition, or halogen-magnesium exchange. Recent reviews have covered the literature in these areas up until 2006. This section covers selected recent advances.

3.3.1 Uses in nucleophilic addition reactions. A relatively rare use of alkyl lithium magnesiates is in nucleophilic addition reactions. Sosnicki has recently highlighted the versatile nature of lithium magnesiates. He has shown that the heteroleptic (although all carbanion) magnesiate LiMg(allyl)(nBu)2 can be used in nucleophilic additions as a key step in the synthesis of δ-thiolactams (Scheme 3).

In a second example, it was discovered that synthons for highly substituted β,γ-unsaturated δ-lactams can be prepared via nucleophilic addition of the aforementioned allyl-containing lithium magnesiate towards selected pyridin-2-ones followed by work-up and then deprotonation of the subsequent parent β,γ-unsaturated δ-lactam using another magnesiate LiMgnBu3. A direct ‘one-pot’ synthesis of these synthons is also possible by simply reacting the starting pyridin-2-one with LiMg(allyl)(nBu)2. Electrophilic quenching of the subsequent magnesiates yields the perhaps unexpected 3,3-disubstituted lactam in high yield along with smaller quantities of the 3,5-dialkylated product (Scheme 4). The reason for the formation of the dialkylated species has been attributed to the generation of nBu2Mg·LiX after the first molecule of R3X has quenched the metallo-intermediate. This new lithium magnesiate (similar to a turbo-Grignard reagent, see Section 5) then itself acts as a base towards the mono-substituted lactam, before this intermediate is quenched to yield the di-alkylated products.

3.3.2 Uses in halogen-magnesium exchange reactions. Highlighting the full gamut of reaction types possible using magnesiates, Sosnicki has employed LiMgnBu3 in bromine-magnesium exchange reactions, to synthesise 5-functionalised 2-methoxypyridines from 5-bromo-2-methoxypyridine. These can subsequently be converted to bicyclic dlactams. Ito and Morita et al. have shown that by utilising palladium-catalysed cross-coupling between haloazulenes and thienyl magnesiate species (prepared from LiMgnBu3 and bromothiophenes), thienylazulenes are prepared in good yield (Scheme 5).

One main advantage of using magnesiates for halogen-magnesium exchange is that selective one site exchange is possible when more than two halogens are present. For instance, McCullough and co-workers have used LiMgnBu3 to undertake selective one-site bromine-magnesium exchange of dibrominated arenes or heterocycles such as 9,9-dioctyl-2,7-dibromo-fluorene, 2,5-dibromo-N-dodecylpyrrole and 2,7dibromo-N-octylcarbazole (also achievable using turbo-Grignard reagents, see Section 4). The resultant magnesiates were successfully employed in Grignard Metathesis (GRIM) polymerisation, mediated by a Ni(II) salt (Scheme 6).

Gleiter et al.have utilised the higher magnesiate “Li2MgnBu4″ in the first step of their synthesis of [24]metacyclophanedienediyne (Scheme 7). Here 1,5-diiodo-2,4-dimethylbenzene was converted to 5-iodo-2,4-dimethylben-zaldehyde (via a single iodine-magnesium exchange using a LiMgnBu3/ nBuLi mixture). This mono-iodo aryl-aldehyde was subsequently used to prepare the aforementioned cyclophane. Balsells and Li have shown that aryl di- or tribromides can be smoothly converted to t-butyl benzoates in excellent yields using selective monobromine-magnesium exchange (LiMgnBu3 is the reagent of choice) followed by reaction with di-t-butyl dicarbonate. Dibromopyridines cannot be converted to their respective carbonates using this methodology.

Gallou and co-workers have utilised several lithium trialkylmagnesiate complexes to prepare lithium triarylmagnesiates (via bromine-magnesium exchange) from various bromoaryls at non-cryogenic temperatures. The most striking feature of this process is that the initial lithium magnesiate species is not pre-formed but is actually generated in-situ by firstly combining a bromoaryl with a Grignard reagent, in a 3:1 molar ratio (at this juncture no reaction occurs) and then by adding two molar equivalents of nBuLi. This ultimately allowed the synthesis of several functionalised arenes including those prepared via nickel-catalysed Kumada-Corriu cross-coupling reactions (Scheme 8). Lau and coworkers have also taken advantage of Kumada-Corriu nickel-catalysed cross-coupling reactions. They converted electron-rich aryl bromides by bromine-magnesium exchange to their respective lithium triarylmagnesiates, and coupled these with several aryl and alkenyl halides, tri?ates and tosylates.

3.3.3 Uses in metallation reactions. Mongin and Abarca et al. have recently shown that LiMgnBu3 can be used to deprotonate [1,2,3]triazolo[1,5-a]pyridines at – 10°C (Scheme 9). The resultant lithium arylmagnesiates can be functionalised by reaction with iodine or 3,4,5-trimethoxy-benzaldehyde although efforts to prepare cross-coupled products using 2-bromopyridine with palladium catalysis were not successful due to the low stability of the lithium arylmagnesiate. Marsais and co-workers have used LiMgnBu3 and other mixed alkyl/amido magnesiates (see Section 6) to effect the deprotonation of several pyridine carboxamides at ambient temperature. No nucleophilic addition towards the pyridine molecule was detected (Scheme 9).

4 Chemistry of the turbo-Grignard reagent iPrMgCl·LiCl

Grignard reagents have long been utilised in organic chemistry primarily as sources of carbanions for use in nucleophilic addition reactions. More recently reagents such as iPrMgCl in THF have been exploited in iodine- magnesium exchange reactions to prepare new functionalised aryl and heteroaryl compounds.

In 2004, Knochel revealed his new bimetallic reagent iPrMgCl·LiCl (later coined as a turbo-Grignard), prepared by combining iPrCl, Mg and LiCl in a 1:1.1:1 ratio in THF. This turbo-Grignard can be used to perform bromine-magnesium exchange reactions at highly enhanced rates when compared to its monometallic iPrMgCl parent, and in the presence of various highly reactive functional groups which cannot be tolerated by an organolithium. Two years later, a new member of this family, iPr2Mg·LiCl was revealed. Recently, the utilisation of turbo-Grignard reagents in synthesis has been reviewed. In this section selected highlights of the usage and scope of iPrMgCl·LiCl from 2008 will be covered.

4.1 Structural chemistry of turbo-Grignard reagents

To date, no structural data for the aforementioned isopropyl turbo-Grignard reagents are available. However, the X-ray structures of three related complexes have been published, which may act as a useful guide to the expected structures of Knochel’s reagents. These three bromide-containing complexes (synthesised by Eaborn and Smith et al.) all adopt rather similar structural motifs and crystallise as monomeric bimetallic complexes with the general formula (donor 1)xLi(Br)2Mg(alkyl)(donor 2)y(Fig. 2).

The first of these structures [(a) in Fig. 2] contains the bulky super-silylmethyl anion and the metals are both solvated by THF. The example which contains a phenyl-substituted supersilylmethyl anion [(b) in Fig. 2] is structurally similar and contains an identical Li-Br-Mg-Br four-membered ring. The Li is solvated by TMEDA and Mg by THF. In the third example [(c) in Fig. 2], a pyridine-substituted supersilymethyl anion is employed, which acts as an internal donor towards Mg. The Li coordinates to three THF moleules resulting in the need for only one Li-Br bond; hence, the aforementioned four-membered ring does not form in this instance.

4.2 Synthetic chemistry of turbo-Grignard reagents

Building upon his initial discovery, Knochel has vastly explored the synthetic applications of turbo-Grignard chemistry. For example, he has converted (hetero)aryl bromides to fluorides in a one-pot procedure by treating the former with iPrMgCl·LiCl to induce Br-Mg exchange and then by electrophilic fluorination of the in-situ organomagnesium reagent with N-fluorobenzenesulfonimide (Scheme 10). The paper immediately following this report in Angewandte Chemie by Beller et al., used a similar methodology to create aryl fluorides, except their fluorinating reagent of choice was N-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate.

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