Mechanism of the Transmetalation of Organosilanes to Gold

Abstract Density functional theory (DFT) calculations were carried out to study the reaction mechanism of the first transmetalation of organosilanes to gold as a cheap fluoride‐free process. The versatile gold(I) complex [Au(OH)(IPr)] permits very straightforward access to a series of aryl‐, vinyl‐, and alkylgold silanolates by reaction with the appropriate silane reagent. These silanolate compounds are key intermediates in a fluoride‐free process that results in the net transmetalation of organosilanes to gold, rather than the classic activation of silanes as silicates using external fluoride sources. However, here we propose that the gold silanolate is not the active species (as proposed during experimental studies) but is, in fact, a resting state during the transmetalation process, as a concerted step is preferred.


Introduction
Thankst ot he "gold rush" of the last two decades, [1,2] gold catalysis [1] has enabled av ast range of exciting and useful transformations of organic molecules. [3,4] Homogeneous gold catalysis is most often mediated by gold(I) complexes bearing N-heterocyclic carbene( NHC) or phosphine ligands, [5] which can exhibit variousm odes of reactivity such as the activation of pacids [6] or complex mechanistic pathways involving carbene species. [7] More recently,t he involvement of multiple gold centers hasb een shown to allow new and interesting transformations. [8] Nolan and co-workers have contributed to this area by developingt he chemistryo fg old(I) hydroxide complexes. [9] These complexes can be activatedb ya cid to form active "[Au(NHC)] + "c omplexes without the need for silver salts, [10] or can effect the activation of ar ange of suitable CÀH/OÀH bonds (where pK a < 30.3) [11] and also CÀCb onds. [12] Upon reaction with boronic acids and silanes, transmetalation results, providing new (typically air-stable) organogold(I)c omplexes (Scheme 1i llustrates some of these pathways with [Au(OH)(IPr)] (1)). [13,14] These complexes therefore hold promise for the development of useful and selective catalytic transformations, as mechanistic probes, and can allow reactions to proceedt hrough mechanismso ther than the classical activation of p-acid substrates. Understanding the reactivity of this Densityf unctional theory( DFT) calculations were carried out to study the reaction mechanism of the first transmetalation of organosilanes to gold as acheap fluoride-free process. The versatile gold(I)c omplex[ Au(OH)(IPr)] permits very straightforward access to as eries of aryl-, vinyl-, and alkylgold silanolates by reaction with the appropriate silane reagent. These silanolate compounds are key intermediates in af luoride-free pro-cess that resultsi nt he net transmetalationo fo rganosilanes to gold, rather than the classic activation of silanesa ss ilicates using externalf luorides ources. However,h ere we propose that the gold silanolate is not the active species (as proposed during experimental studies) but is, in fact, ar estings tate during the transmetalation process, as ac oncerted step is preferred.
class of complexes is critically important,a si ta llows us to fully exploit it in catalysis and in organic synthesis.
Transmetalation of ag roup from one metal (or metalloid) speciest oa nother is ak ey step in metal-catalyzed crosscoupling reactions. Each example is distinct and can proceed through ad ifferent mechanism.F or example there has been some debate recently regarding whether transmetalation in Suzuki-Miyaura reactions [15] occurs via an organopalladium(II) halide andaboronate molecule, or via an organopalladium(II) hydroxide and ab oronic acid. [16] Few intermediates en route to transmetalation have been isolated and fully characterized. In this field, transmetalation to gold is of current interest, [9,17,18] due to the potential to develop dual catalysis with gold and palladium, nickel,orr hodium, for example. [19] Nolan and Dupuy have recently studied the transmetalation of silanes with gold(I)h ydroxide complexes. [20] In contrastt o traditional transmetalation pathways involvings ilanes (e.g. the Hiyama cross-coupling), [21] no anionic fluoridew as necessary to promotet he reaction (Scheme 2). While reactions with simple silanes such as PhSiMe 3 led to no product, silanolate species 2 weref ormed rapidly when 1 was exposed to aryltrialkoxysilanes, and these then evolved to the desired arylgold(I) species 3 on heating. Three possible mechanistic hypotheses were put forward: 1) electrophilic aromatic substitution to form aW heland intermediate, followed by the loss of as ilicate leaving group,2 )a concerted mechanism, proceeding throughaf our-membered transition state, or 3) activation of the silane as as ilicate, followed by ac oncerted transmetalation.
Interestingly,e xperimentally,t his reactionw as found to proceed far more rapidly when 1 was exposed to silane, compared with startingf rom isolatedg old silanoate 2,w hich stalled after 50 %c onversion. For both reactions, the formation of pink particles waso bserved over time implying decomposition of the gold complext og old(0) nanoparticles. These findings strongly emphasized the non-innocent role of the molecule of methanol generated in situ when forming intermediate 2 before the subsequentt ransmetalation reaction. Certain of the benefits of methanol on reactivity,b oth reactions were repeated in methanola t8 08C. Alas, no trace of 3 could be detected after 24 h. However,t he addition of increased amounts of dry methanol, under these reactionconditions, provedtoeffectively enhancet he overall rate of the transmetalation.
To shed light on the mechanism of the transmetalation of organosilanes to gold, density functional theory (DFT) calculations were performed, as these allow ag reater depth of insight into the individual steps of this fluoride-free transmetalation than experimentalresults.

Results and Discussion
The reactionpathways that best link the organosilane reactantt ot he organogold product are displayed in Scheme3,b earing af luoride-free route. The first common step highlighted by calculations of the reaction of trimethoxyphenylsilane with 1 leads to aweakly-bound species 4 which holds apentacoordinate silicon centre. The barrier to this intermediate (TS1)i so nly 11.8 kcal mol À1 (Figure 1), with the Scheme3.Calculated pathways for the transmetalation of silanes to gold(I) hydroxide 1.
Intermediate 4 undergoes to ap rotont ransfer from the AuÀ OH moiety to one of the OMe groups of the silane resulting in the elimination of methanolw ith formation of product 5. The energy barrierf or this process is 14.6 kcal mol À1 .E ven though this barrier is ratherh igh in comparison with experimental findings, [20] it is stilla chievable at room temperature (TS2 in Figure 1). Gold siloxane 5 and methanola re 5.7 kcal mol À1 more stable than 1 plus silane.
From this point forward, two mechanisms were sought through which 5 could evolve into phenylg old 3 and as ilicon byproduct, which are placed 21.8 kcal mol À1 below 1 plus silane. With regard to preliminary experiments, [20] and similar to Denmark's work, [22] the pathways envisioned for the transmetalation from silicon to gold (Scheme 4) are:1 )ana nionic pathway whereby the molecule of methanol, generatedi ns itu, would act as an ucleophilic activator,g enerating ap entacoordinated gold silicates pecies 6 which is poised for transmetalation and 2) at hermalp athway that would proceed via ac oncerted mechanism through TS4. The latter pathway would most likely be more challenging and thus may rationalize the difference in reactivity when using an onpolar solvent such as toluene versus1,4-dioxane.
Attempts to locate the proposed intermediate 6 were unsuccessful. The most feasible pathway found was through transition state TS4,w hich releases ah igh energy Si(O)(OMe) 2 molecule that can react in ab arrierless step with am ethanol molecule leadingt ot he final gold complex 3 and Si(OMe) 3 OH. TS4 lies 17.1 kcal mol À1 above 1 plus silane and more importantly,2 2.8 kcal mol À1 above 5, from which it defines the upper energy barrier in Figure1.Finally, an alternative reaction involving the direct activationo ft he SiÀPh bond in 4 by the AuÀOH bond in as ingle concerted step was explored. In this context, transition state TS3 was located, 15.1 kcal mol À1 above 1 plus silane (10.0 kcal mol À1 above 4), which connects intermediate 4 to the final products in as ingle step ( Figure 1). All transition states are represented in Figure 2.
The overall mechanistic scenario emerging from Figure1 is ratherc omplicated. These computational results point out that the formation of gold adduct 4 through TS1 is feasible kinetically,a nd this intermediate can be considered as the key intermediate in the reaction. Twoa lternative pathways were located for the transmetalationr eaction to proceed from 4.F rom 4, the reactionc ould go through TS2 to give 5 and then via af our-membered transition state TS4 to eliminateasilicon byproduct and produce 3.A lternatively,t he second possibility is the direct transmetalationp rocess from 4 through TS3 leading to phenyl gold complex 3.C onsidering the differencei n Scheme4.Proposed reaction pathways for the aryl transfer from the siloxane to gold(I).
ChemistryOpen 2016, 5,60-64 www.chemistryopen.org energy of 4.6 kcal mol À1 between the determining transition states of the two pathways,the latter is likely to be favored.
In the context of the experimental results, this potential energy surfacei ss ensible. While the mixing of 1 and silane has been shownt oy ield isolable species such as 5,t he isolated complex 5 is known to undergo transmetalationm uch slower than the combinationo f1 and silane. While this was interpreted as implying as pecialr ole for methanol, liberated during this first step, in the subsequent transmetalations tep, it could insteadp oint to the reversible formation of 5,f rom the computational results. In fact, complex 5 faces a2 5.4 kcal mol À1 barriert or eform species 4,w hich mayb es urmounted under the high temperature conditions used, despite a22.8 kcal mol À1 barriert ot ransmetalation.I nc ontrast, 4 faces only a1 0.0 kcal mol À1 barrier to direct transmetalation. We therefore propose that, in solution, 5 is ar esting state lying off the transmetalation pathway in ap otential energy well, and that it is not at rue intermediate in the reaction;i tm ust first be (re)converted to 4.

Conclusions
We have shed light upon this new synthetic approacht oN HCaryl-, vinyl-, and allyl-gold systems. This is the first computational study of at ransmetalation of organosilanes to gold under fluoride-freec onditions, representing ad ifferent reactivity manifold than the classic activation of silanes as silicates using external fluorides ources. [23] The present results provide the first key insight into the mechanism of transfero ft he organic fragment from silane to gold and establishes that the reactivity of gold is similar to that of palladiumi nt he Hiyamatype coupling. We proposet hat the gold silanolate is not the active species (as proposed during experimental studies) but is, in fact, ar esting state during the transmetalation process, as ac oncerted step is preferred. The potential energy surface in Figure 1e xplainsw hy isolated 5 undergoes aryl transfer to gold much slower than mixing 1 and silane directly.T he basic understanding of this transmetalation reactiono fs ilanes lays the groundwork for further exciting studies in this area

Computational Details
All DFT calculations were completed with the Gaussian09 set of programs. [24] For geometry optimizations, the well-established and computationally fast generalized gradient approximation (GGA) functional BP86 was used. [25] Geometry optimizations were performed without symmetry constraints, while located stationary points were characterized by analytical frequency calculations. The electronic configuration of the molecular systems was described with the split valence polarized (SVP) basis set with ap olarization function for H, C, N, Si, and O. [26] For Au, we used the small-core, quasi-relativistic Stuttgart/Dresden effective core potential with an associated valence contracted basis set (standard SDD keywords in Gaussian 09). [27] Zero-point energies and thermal corrections were calculated at the BP86 level. Singlepoint energy calculations with the M06 functional [28] in solution were performed with the triple-zeta valence with polarization (TZVP) basis set for main group atoms and again the same SDD pseudopotential for Au. Solvent effects were included with the polarizable continuous solvation model (PCM) using 1,4-dioxane as as olvent. [29] The reported free energies in this work include energies obtained at the M06/TZVP level corrected with zero-point energies, thermal corrections, and entropy effects evaluated at 298 K and 1354 atm [30] with the BP86/SVP method in the gas phase.