DETERMINACIÓN DE LOS PRECIOS UNITARIOS DE LOS CONCEPTOS NO PREVISTOS EN EL CATÁLOGO ORIGINAL

Transmetallation agents are frequently used in coupling reactions where they are crucial in the transfer of an organic functional group to a metal centre.1 _{Gold itself has been used in the}

transmetallation of other metal centres including nickel, palladium, platinum, iron, titanium and rhodium.2 _{This reactivity has been applied to bimetallic catalysis, where gold has been}

employed as a transmetallating agent to other gold centres or group 11 catalysts.3 _More

recently, p-block compounds have been used in the transmetallation of gold centres.

4.1.1 Boronic acids in transmetallation reactions

Boronic acids have proved to be versatile building blocks in organic synthesis, specifically in palladium catalysed cross-coupling reactions.4 _{The best-known of these palladium cross-}

coupling reactions is the Suzuki-Miyaura reaction, in which transmetallation of Pd–X bonds by boronic acids in the presence of a base forms Pd–C bonds, and subsequent reductive elimination from this species leads to C-C bond formation (see Section 3.1).5

Boronic acids have also been used in the transmetallation of Au–X bonds in both gold(I) and gold(III) systems. Transmetallation of gold(I) halide bonds (X = Cl, Br) by boronic acids requires the presence of caesium carbonate acting as a base (a, Scheme 4.1); complete conversion was observed upon heating to 50 °C.6 _{Altering the base to potassium hydroxide}

facilitates conversion at room temperature (b, Scheme 4.1).7 _{This was proposed to go through}

either the in situ formation of a gold hydroxide species or a borate.

Scheme 4.1. The transmetallation of gold(I) species by boronic acids.

The base-free transmetallation of (C^N^C)gold(III) hydroxide with boronic acids was observed upon heating to 60 °C and was compatible with a range of aryl and heterocycle boronic acids (Scheme 4.2).8 _{The gold(III) aryl complexes formed were shown to be}

83 photoemissive. This protocol has since been applied to the synthesis of highly luminescent gold(III) aryls that have been used in OLED devices.9

Scheme 4.2. The transmetallation of a gold(III) hydroxide by boronic acids.

Alternately, gold(III) aryls can be synthesised through the coupling of an Au–Cl bond with a boronic acid by using a palladium catalyst in the presence of a base at elevated temperatures (Scheme 4.3).10 _{The gold(III) aryls produced are again highly luminescent.}

Scheme 4.3. The coupling of an Au-Cl bond with a boronic acid using a palladium catalyst.

Under more forcing conditions (heating to 150 °C), the base and catalyst free transmetallation of gold(III) chloride using a boronic acid was achived.11 _{This reaction is only compatible with}

electron-deficient aryl boronic acids, limiting the scope of the reaction. A C^C^N gold(III) fluoride complex required slightly less harsh conditions (heating to 70 °C) to facilitate the transmetallation of an Au–F bond by a boronic acid, however it only proceeded with electron- deficient fluoroaryl boronic acids (Scheme 4.4).12

84 A C^N-stabilised gold(III) difluoride underwent facile transmetallation using boronic acids (conversion is observed at room temperature), however it is also able to undergo reductive elimination with C-C coupling products observed.12 _{Similarly, the transmetallation of Au–F}

bonds by boronic acids in other gold complexes has been proposed, however only the C–C coupling products formed upon reductive elimination are observed.13

More recently, boronic acids have been used in a range of catalytic gold coupling reactions. Chapter Three, Figure 3.2, showed the use of a boronic acid in catalytic oxidative arylation.14

Boronic acids have also been used in the gold catalysed coupling of allyl halides with aryl boronic acids15 _{and coupling of terminal alkynes with boronic acids.}16

4.1.2 Transmetallation using organozinc reagents

Organozinc reagents are also widely used in synthetic chemistry, although they are less air stable than boronic acids, but they are more tolerant of functional groups than the corresponding magnesium or lithium reagents.17 _{Different organozinc reagents have varying}

reactivity; dialkyl zinc reagents are much more reactive than the corresponding alkyl zinc halides. In palladium catalysis, organozinc reagents are used as transmetallation reagents in the Negishi coupling reaction that couples an organozinc reagent and an organohalide to form a new C–C bond.18 _{In this reaction oxidative addition of the organohalide C–X bond forms a}

palladium(II) complex, this is followed by transmetallation of a Pd–X bond by an organozinc halide which forms a Pd–C bond and subsequent reductive elimination forms a new C–C bond. Another palladium catalysed reaction that is relevant to this work is the Fukuyama reaction because it involves the formation of a metal-thiolate species and M–S bond transmetallation. The Fukuyama reaction couples a thioester and organozinc reagent to form a ketone (Scheme 4.5).19 _{The mechanism is proposed to go via oxidative addition of a thioester to palladium,}

followed by the transmetallation of a Pd–S bond by organozinc reagent and subsequent reductive elimination forming a C–C bond. The thioester can be synthesised from carboxylic acids with the overall transformation of carboxylic acid to ketone.

Scheme 4.5. The Fukuyama reaction.

Despite the wide use of organozinc reagents with other transition metals the reports of reactivity with gold are limited to two reactions. Firstly, the reaction of (Ph3P)AuCl with B

85 results in both transmetallation and displacement of the phosphine to give two Au–C bonds (Scheme 4.6).20

Scheme 4.6. The reaction of an organozinc reagent with a gold(I) complex.

The second example uses adamantylzinc bromides (both 1-AdZnBr and 2-AdZnBr, Ad = adamantyl), which can be reduced to the corresponding diadamantylzincs to give four different organozinc reagents.21 _{All four of these complexes can be used in the transmetallation of}

(R3P)AuCl to give a new Au–C bond (Scheme 4.7). When the adamantylzinc bromides were

used the product could not be isolated and instead were only observed in situ. The diadamantylzinc compounds proved to be superior reagents for transmetallation of the Au–Cl bond allowing isolation of (R3P)AuAd .

Scheme 4.7. An organozinc reagent transmetallating an Au–Cl bond.

4.1.3 Silanes and stannanes in transmetallation reactions

Other p-block compounds have been investigated as transmetallation reagents with both gold and other transition metals. Silyl reagents are used in transition metal cross couplings catalysis,22 _{such as the palladium catalysed Hiyama coupling, which uses organic halides and}

organosilanes to give a carbon–carbon bond.23

The reactivity of gold complexes and a range of silanes has shown them to be transmetallation reagents.1 _{The stoichiometric transmetallation of Au–O bonds with R-Si(OMe)}

3 has been

demonstrated for gold(I) species (Scheme 4.8).24 _{The intermediates in this reaction can be}

isolated and characterised and contain an oxygen bonded to both gold and silane. A wide range of functional groups were shown to be transferred to gold, including aryls, vinyls and allyls.

86 Trimethylarylsilanes were used to transfer an aryl group to gold in gold-catalysed oxidative arylation (Scheme 4.9).25 _{A comprehensive mechanistic study into this catalytic reaction}

allowed elucidation of the mechanism. A simplified description of this includes: oxidation of the gold(I) complex by a hypervalent iodine species, this undergoes electrophilic aromatic substitution of a silane and subsequent C–H auration of an aryl C–H bond; finally, reductive elimination forms a C–C bond and regenerates the gold(I) complex.

Scheme 4.9. Arylsilanes in gold catalysed oxidative arylation.

The use of stannanes in palladium catalysis is well known; the Stille reaction couples stannanes with organic electrophiles.26 _{Stannanes have also been used in the transmetallation}

of gold species, such as in the formation of the gem-diaurated furyl complex (Scheme 4.10).27

Identification of this reaction was part of a study on gold(I) catalysed cyclisation and stannyl transfer.

Scheme 4.10. Transmetallation of a gold(I) species using stannanes.

Other transmetallation reactions using both stannanes and gold have involved bimetallic catalysis where catalytic amounts of Pd/Au allow the addition of stannanes to alkynes.28 _In

this reaction the gold was proposed to activate the alkyne.