3.5.13 Silver-Promoted Coupling Reactions

J.-M. Weibel, A. Blanc, and P. Pale

General Introduction

After the emergence of organometallic chemistry in the middle of the 19th century with Frankland's report of the first organozincs,[1] the rich organomagnesium chemistry promoted by Grignard at the turn of the 20th century stimulated the exploration of related reactivity with zinc, cadmium, mercury, copper, silver, and gold. Although remaining at that time mostly based on stoichiometric amounts of their salts and organometallics, these metals nevertheless offered interesting methods for the formation of C-C bonds, one of the key transformations in organic synthesis. Since these early developments, techniques and methods have evolved to provide numerous routes to establish C-C bonds based on the properties of the salts and/or organometallics of these metals. Among them, silver salts and the corresponding organometallics have been widely applied. However, for a long time, silver salts were mostly used as halide scavengers in many reactions, from nucleophilic substitutions to eliminations and rearrangements, through organometallic activation. Nevertheless, the organometallic chemistry of silver has steadily evolved, mostly focusing on the access to these organometallics and on some applications. In parallel, the peculiar properties of silver and its derivatives have allowed various, often new, transformations to be performed under mild conditions, establishing silver and its derivatives as unique tools in organic synthesis.[2-6] The organic chemistry of silver has bloomed since the beginning of the 21st century (? Figure 1).[7]

Figure 1 Number of Published Papers Involving Silver and Organic Synthesis between 1879 and 2014 (from a SciFinder Analysis Performed in 2015)

Although less intense than in the case of gold, silver benefits from relativistic effects (? Figure 2).[8] The latter imposes s- and p-orbital contractions, leading to their stabilization and thus to a lower HOMO for Ag0 but to a lower LUMO for Ag+. Indirectly, these effects generate d- and f-orbital dilatation and lead to their destabilization. The latter, as well as an increased spin-orbit coupling, gives a higher HOMO to Ag+. Furthermore, increased backdonation can take place, giving some stabilization to alkenyl, aryl, alkynyl, and even carbene organosilver compounds and rendering them more nucleophilic. Silver(I) salts are thus reactive as Lewis acids, in particular with unsaturated systems having low-lying empty orbitals, especially alkynes. The chemistry of silver is thus driven by these properties, through the formation of s-, p-, carbene, and carbonyl complexes (? Table 1).[9]

Figure 2 Influence of Relativistic Effects on the Frontier Orbitals of the Coinage Metals[8]

Table 1 Comparison of the s- and p-Coordination Ability of the Coinage Metals [Calculated ?Hf (kcalmol-1)][9]

  BCl3 CuCl AgCl AuCl AuCl3 PhC=CH 0.9 33.1 22.6 34.7 32.5 PhCH=CH2 0.4 33.6 24.4 37.5 36.8 PhCHO 18.9 37.4 26.4 33.1 35.9

The purpose of this chapter is to cover synthetic applications of silver for the formation of C-C bonds through coupling reactions. These encompass a variety of reactions promoted by a metal catalyst, in which new C-C bonds are created. For silver and its salts and complexes, the corresponding organic chemistry can be divided according to the properties mentioned above, i.e. into the nucleophilic behavior of organosilver compounds, the role of silver as s-Lewis acid, and the involvement of silver in homocoupling and cross-coupling reactions. In the present contribution, we will only focus on the nucleophilic behavior, homocoupling, and cross-coupling reactions of organosilver compounds.

3.5.13.1 Organosilver Compounds as Nucleophiles

3.5.13.1.1 Nucleophilic Substitution

3.5.13.1.1.1 Method 1: Alkylations with Organosilver Compounds

As is the case with most organometallics, organosilver compounds are often aggregates. This structural feature limits their reactivity to a certain extent, and especially their nucleophilicity. Nevertheless, a few examples are known, mostly involving silver acetylides.

3.5.13.1.1.1.1 Variation 1: Reactions of Silver Acetylides with Alkyl Halides

Although polymeric substances,[10] silver acetylides can react as nucleophiles with various alkyl halides, provided that the reaction is performed in polar solvents, probably to dissociate the organometallic polymer. Such reactions provide the corresponding disubstituted acetylenes in good to high yields. The silver acetylide 1 derived from methyl undec-10-ynoate reacts with neat iodomethane or iodoethane to give the corresponding alkylated acetylene derivatives (e.g., 2) (? Scheme 1).[11] Silver acetylides (e.g., 3) can even react with 1-adamantyl bromide or iodide and related bridged systems, such as bicyclo[2.2.2]octanes, in refluxing N-methylmorpholine or pyridine, to furnish 1-adamantylated acetylenes 4, probably through an SRN1 mechanism (? Scheme 2).[12,13]

Scheme 1 Alkylation of a Silver Acetylide[11]

Scheme 2 Alkylation of Silver Acetylides with 1-Iodoadamantane[13]

R1 R2 Yield (%) Ref H H 68 [13] H (CH2)4Me 57 [13] Cl H 62 [13] H Br 20 [13]

Methyl Dodec-10-ynoate (2):[11]

CAUTION:

Iodomethane is a carcinogen. Proper precautions should be taken during its handling.

A mixture of (11-methoxy-11-oxoundec-1-ynyl) silver (1; 12.7 g, 42 mmol) and MeI (10 mL) was heated at 75 °C in a sealed tube overnight. The solid was filtered off and washed with Et2O. The solvent was removed from the filtrate by distillation, and the residue was distilled under reduced pressure from a Späth bulb in an air furnace at 85 °C; yield: 4 mL (45%).

1-(Arylethynyl) adamantanes 4; General Procedure:[13]

CAUTION:

Sodium azide can explode on heating and is highly toxic. Contact of metal azides with acids liberates the highly toxic and explosive hydrazoic acid.

A silver(I) arylacetylide 3 (2 equiv) was added to a soln of 1-iodoadamantane (100 mg, 0.38 mmol, 1 equiv) in anhyd N-methylmorpholine (3 mL), and the resulting suspension was heated at reflux under argon in the dark for 16-24 h. The solvent was removed under reduced pressure, and the residue was diluted with CH2Cl2 (ca. 3 mL). The mixture was passed through Celite, and the filtrate was washed with 0.1 M aq NaN3 (20 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, petroleum ether (40-60 °C)] to afford the product, which was then recrystallized (petroleum ether).

3.5.13.1.1.1.2 Variation 2: Reactions of Alkenylsilver Compounds with Alkyl Halides

In their studies of the mechanism of reactions of organosilver compounds, Casey et al. showed that vinylsilver compounds (e.g., 5), easily obtained by transmetalation from the corresponding Grignard reagents, stereoselectively react with bromomethane.[14,15] The observed retention of stereochemistry suggests a nucleophilic displacement (? Scheme 3).

Scheme 3 Nucleophilic Substitution Reaction of a Vinylsilver Compound[14,15]

3.5.13.1.1.2 Method 2: Epoxide Opening with Silver Acetylides

Epoxides are reactive electrophiles that can be readily opened by various nucleophiles including acetylides. Silver acetylides (e.g., 6) are no exception and indeed react with epoxides 7, although activation by dichlorobis (?5-cyclopentadienyl) zirconium (IV) [Zr (Cp)2Cl2] and silver(I) trifluoromethanesulfonate is required.[16] Interestingly, propargylic alcohols 8 and not the classical homopropargylic alcohols are obtained (? Scheme 4). The mechanism, as evidenced by NMR studies, involves an epoxide to aldehyde rearrangement before the alkynylation step (? Scheme 4). This method is compatible with various functional groups and both electron-rich and -deficient alkynes, and efficiently provides functionalized propargylic alcohols in good to high yields.

Scheme 4 Reaction of Epoxides with...