1,2-Addition of Diethylzinc to a Bis(Imidazolyl)ketone Ligand.

In this study, the selective 1,2-addition of diethylzinc to the ketone functionality of BMdiPhIK [bis(1-methyl-4,5-diphenylimidazolyl)ketone] is shown. The reaction product is isolated in a dimeric form with a planar Zn2(µ-O)2-motif keeping the two monomers together. This compound can serve as a model for reactive intermediates in the catalytic alkylation of ketones with diorganozinc reagents. Hydrolysis of this binuclear zinc compound leads to isolation of the C-alkylated product in 89 % yield. A reaction pathway is proposed in which BMdiPhIK initially coordinates to diethylzinc as a bidentate bis(nitrogen) ligand. This is followed by the homolytic cleavage of the Zn-Et bond and in-cage recombination of the Et-radical and the Zn-coordinated ligand-centered radical, which is mainly localized on the carbonyl moiety of the ligand.

Introduction

n class="Chemical">Diorganozinc reagents are widely used as selective alkylaticlass="Chemical">ng ageclass="Chemical">nts for the alkylatioclass="Chemical">n of fuclass="Chemical">nctioclass="Chemical">nalized electrophiles iclass="Chemical">n orgaclass="Chemical">nic syclass="Chemical">nthesis1 Furthermore, they caclass="Chemical">n be used iclass="Chemical">n Pd‐ aclass="Chemical">nd Ni‐catalyzed cross‐coupliclass="Chemical">ng reactioclass="Chemical">ns for class="Chemical">n class="Chemical">carbon–carbon bond formation.2 Other applications in organic synthesis are the (enantioselective) addition to aldehydes, ketones, and imines, the conjugate addition to α,β‐unsaturated compounds,3 the direct addition to alkenes and alkynes,4, 5 and as radical initiators.6, 7, 8

Much research has focused on the use of din class="Chemical">alkylzinc reagents iclass="Chemical">n the alkylatioclass="Chemical">n of aldehydes,9, 10, 11, 12 while the alkylatioclass="Chemical">n of class="Chemical">n class="Chemical">ketones is more challenging and often a Ti‐ or Al‐containing activator is used in the addition of diorganozinc compounds to a ketone.13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 Due to the possible formation of Zn‐enolate compounds from α‐acidic ketones or the formation of self‐aldol products, the addition of organozinc compounds to ketones is often not successful.25 Additionally, ketones are generally less reactive than aldehydes. The first literature example of the addition of an organozinc reagent (Ph2Zn) to a ketone without the need of a Ti‐activator dates from 1998 by Fu et al.,26 while the first example using Et2Zn by Ishihara et al., dates only from 2007.27 Both examples make use of catalytic amounts of an organic ligand. Ishihara et al. used chiral phosphoramide–ZnII complexes as conjugate acid–base catalysts for enantioselective organozinc C‐addition to ketones (vide supra). On the other hand, Fu et al. used 3‐exo‐(dimethylamino)isoborneol (DAIB) in the presence of MeOH as chiral catalyst for the enantioselective addition of ZnPh2 to a range of aryl‐alkyl and dialkyl ketones. In the past decade more examples of the addition of Et2Zn to ketones have been reported, including enantioselective examples.25, 28, 29, 30, 31 Typically, only catalytic amounts of (chiral) ligand are used, while stoichiometric amounts of alkylzinc are needed and generally only one of the alkyl ligands is successfully transferred to the substrate.

Ishihara et al. proposed a polar mechanism for the catalytic enantioselective ethylation of n class="Chemical">ketones with class="Chemical">n class="Chemical">Et2Zn.27 The transition state of this mechanism involves two zinc centers, of which one activates the incoming ketone and is coordinated to the chiral ligand, while the other acts as the alkyl transfer reagent. Lewis acid–base interactions between the catalytic zinc center and the carbonyl group of the ketone substrate and between the P=O moiety of the phosphoramide ligand and the Et2Zn zinc center bring the reagents in close proximity and in the right orientation for alkyl transfer to take place (Figure 1, left).

Figure 1

Left: Proposed transition state for the catalytic enantioselective ethylation of ketones with Et2Zn.27 Right: Schematic representation of the Zn2(µ‐O)2‐motif.

Left: Proposed transition state for the catalytic enantioselective ethylation of n class="Chemical">ketones with class="Chemical">n class="Chemical">Et2Zn.27 Right: Schematic representation of the Zn2(µ‐O)2‐motif.

The catalytic addition of an alkylzinc to a n class="Chemical">carbonyl moiety most likely leads to the formatioclass="Chemical">n of class="Chemical">n class="Chemical">zinc alkoxide intermediates, which are generally not isolated. In the presence of potentially multi‐electron donating alkoxide groups, three‐coordinate zinc compounds tend to aggregate via oxygen bridges to attain the preferred tetrahedral geometry around the zinc center. This aggregation can lead to the formation of a central planar Zn2(µ‐O)2‐motif (Figure 1, right), which is a very common structural motif for which many solid‐state structures have been determined, while the formation of higher aggregates is also observed.32

In 2012, Okuda et al. isolated a dimeric zinc complex with an n class="Chemical">Zn2(µ‐O)2‐motif from the 1,2‐additioclass="Chemical">n of diclass="Chemical">n class="Chemical">allylzinc to benzophenone, showing that one of the allyl‐ligands adds to the ketone moiety and one remains bound to zinc.33 This provided the first example of an isolated Zn‐containing product from the 1,2‐addition of an organozinc compound to a ketone. The dimeric complex is structurally related to the proposed intermediate of the addition of alkylzinc to carbonyls (Scheme 1A).

Scheme 1

A. The 1,2‐addition of allylzinc to benzophenone.33 B. Radical 1,4‐addition of Et2Zn to an α‐iminoketone.34 C. Radical addition of tBu2Zn to dibenzoyl.28 D. Radical 1,4‐addition of Et2Zn to an α‐diimine.36

A. The 1,2‐addition of n class="Chemical">allylzinc to class="Chemical">n class="Chemical">benzophenone.33 B. Radical 1,4‐addition of Et2Zn to an α‐iminoketone.34 C. Radical addition of tBu2Zn to dibenzoyl.28 D. Radical 1,4‐addition of Et2Zn to an α‐diimine.36

While a polar mechanism is proposed for the addition of n class="Chemical">alkylzinc reagents to class="Chemical">n class="Chemical">carbonyls, radical mechanisms are generally proposed for 1,4‐addition reactions, as confirmed by EPR studies.34, 35 Spek et al. have reported on the 1,4‐addition of Et2Zn to an α‐iminoketone leading to N‐alkylation (Scheme 1B).34 For the 1,4‐addition of Et2Zn to dibenzoyl (dbz), leading to the O‐alkylated product, Lewinski et al. also proposed a radical mechanism (Scheme 1C).28 In this reaction, a minor amount of the 1,2‐addition product (C‐alkylation) was also observed.28 Both radical 1,4‐addition reactions result in the formation of dimeric zinc complexes with a Zn2(µ‐O)2‐motif (Scheme 1). Another example of a 1,4‐addition is the addition of alkylzinc reagents to α‐diimines (Scheme 1D).36 For this reaction extensive mechanistic studies were performed leading to the proposal of an inner sphere single electron transfer (SET) mechanism.36, 37 In contrast to the first three examples, the product of the last example is isolated as the monomer because of the lack of multi‐electron donating alkoxide groups.

Here, the stoichiometric reactivity of the bidentate N,N‐ligand n class="Chemical">BMdiPhIK [bis(1‐methyl‐4,5‐dipheclass="Chemical">nylimidazolyl)class="Chemical">n class="Chemical">ketone] with Et2Zn is reported (Scheme 2). With its potentially coordinating nitrogen and carbonyl moieties, this ligand shows similarities to α‐iminoketones as well as α‐diimines for which 1,4‐addition of Et2Zn leading to N‐alkylation is observed.28, 34, 35, 38, 39 However, also addition to the ketone, leading to C‐alkylation is plausible. Because both α‐carbons relative to the carbonyl functionality in the BMdiPhIK ligand lack a proton, the formation of the earlier mentioned Zn‐enolates or self‐aldol products is not possible. While there are several possible reaction pathways of BMdiPhIK with Et2Zn, it turns out that BMdiPhIK undergoes a selective 1,2‐addition with Et2Zn leading to the C‐alkylated product. This selectivity initiated the interest to investigate this reaction further as a stoichiometric example of the 1,2‐addition of an alkylzinc reagent to a carbonyl. In this reaction BMdiPhIK has a bifunctional character, as it is functioning both as ligand and as substrate. As pointed out above, radical pathways are proposed for 1,4‐additions to α‐diimines, α‐iminoketones, and α‐diketones. Previous results on the reduction of BMdiPhIK show that this results in rather stable radicals, indicating that this ligand can provide a good platform to investigate a possible radical pathway towards the alkylation of ketones.40

Scheme 2

The formation of the dimeric zinc complex [Zn2(BMdiPhIAEt)2Et2] from Et2Zn and BMdiPhIK via intermediate product [Zn(BMdiPhIK)Et2] followed by the hydrolysis of the Zn‐dimer to isolate H‐BMdiPhIAEt.

The formation of the dimeric zinc complex [n class="Chemical">Zn2(BMdiPhIAEt)2Et2] from class="Chemical">n class="Chemical">Et2Zn and BMdiPhIK via intermediate product [Zn(BMdiPhIK)Et2] followed by the hydrolysis of the Zn‐dimer to isolate H‐BMdiPhIAEt.

Results and Discussion

1,2‐Addition of Et2Zn to the BMdiPhIK Ligand

Addition of a n class="Chemical">Et2Zn solutioclass="Chemical">n to a suspeclass="Chemical">nsioclass="Chemical">n coclass="Chemical">ntaiclass="Chemical">niclass="Chemical">ng oclass="Chemical">ne equivaleclass="Chemical">nt of bis(1‐methyl‐4,5‐dipheclass="Chemical">nylimidazolyl)class="Chemical">n class="Chemical">ketone (BMdiPhIK) in toluene at –78 °C induced an immediate color change from light yellow to dark red and complete dissolution of the ligand. This color change suggests the formation of coordination complex [Zn(BMdiPhIK)Et2] (Scheme 2) as similar colors are observed for related dialkylzinc diimine complexes.36, 41 When stirring was continued at room temperature, the color disappeared within seconds, leading to a colorless solution from which the binuclear complex [Zn2(BMdiPhIAEt)2Et2] {BMdiPhIAEt: bis(1‐methyl‐4,5‐diphenylimidazol‐2‐yl)ethyl‐alcohol} was obtained in 71 % yield (Scheme 2). In this reaction an uncommon 1,2‐addition of Et2Zn to the ketone in the BMdiPhIK ligand took place. This was unambiguously proven by hydrolysis of the zinc complex and isolation of H‐BMdiPhIAEt in 89 % yield (Scheme 2). The products were identified using 1H and 13C NMR, IR spectroscopy, ESI‐MS, and X‐ray crystal structure determination. Single crystals of [Zn2(BMdiPhIAEt)2Et2] of high quality were obtained from a THF solution by slow vapor diffusion of hexanes.

Using IR spectroscopy, it was found that the strong ν(C=O) band at 1622 cm–1 for n class="Chemical">BMdiPhIK is abseclass="Chemical">nt iclass="Chemical">n the ziclass="Chemical">nc complex iclass="Chemical">ndicaticlass="Chemical">ng the formal reductioclass="Chemical">n of the class="Chemical">n class="Chemical">ketone to an alkoxide. With high‐resolution mass spectrometry a molecular ion was observed at m/z = 1207.3925 (calcd. 1207.3948) corresponding to the binuclear product [Zn2(BMdiPhIAEt)2Et] as drawn in Scheme 2, losing one ethyl ligand. These data strongly suggest the formation of an alkoxide dimer.

This was confirmed by X‐ray crystal structure determination. The molecular geometry of [n class="Chemical">Zn2(BMdiPhIAEt)2Et2] is showclass="Chemical">n iclass="Chemical">n Figure 2 aclass="Chemical">nd selected boclass="Chemical">nd leclass="Chemical">ngths aclass="Chemical">nd aclass="Chemical">ngles are giveclass="Chemical">n iclass="Chemical">n Table 1. The structure shows the formal 1,2‐additioclass="Chemical">n of class="Chemical">n class="Chemical">Et2Zn to the carbonyl of the BMdiPhIK ligand. The resulting dimeric zinc complex has a planar Zn2(µ‐O)2‐motif with an exact, crystallographic inversion center in the middle of this motif. As a consequence of the centrosymmetry, the central Zn2(µ‐O)2 core is exactly planar and both metal atoms are equivalent. Each zinc center is coordinated by one ethyl ligand as well as an imidazole nitrogen atom and two bridging alkoxide groups, resulting in a distorted tetrahedral geometry. The angles at Zn vary between 78.11(7) and 130.00(10)°, resulting in a large angular variance of 491.24°.44 The reason for the distortion is the ring strain in both the four‐ and five‐membered chelate rings.

Figure 2

Left: Molecular structure of [Zn2(BMdiPhIAEt)2Et2] in the crystal. The metal‐bound ethyl group is disordered, only the major disorder component is shown. Hydrogen atoms are omitted for clarity. Displacement ellipsoids are drawn at the 40 % probability level. Right: schematic representation of [Zn2(BMdiPhIAEt)2Et2], chiral centers are indicated with R and S.

Table 1

Selected bond lengths and angles found in [Zn2(BMdiPhIAEt)2Et2]a

	Bond length (Å)		Angle (°)
Zn1–O1	2.0801(16)	O1–Zn1–O1a	87.76(6)
Zn1–O1a	2.0118(16)	Zn1–O1–Zn1a	92.24(6)
Zn1–N11	2.077(2)	O1–Zn1–N11	78.11(7)
Zn1–C4	1.972(3)	O1–Zn1–C4	123.93(11)
O1–C1	1.409(3)	N11–Zn1–C4	124.37(12)
Zn1···Zn1a	2.9497(6)	N11–Zn1–O1a	97.24(7)
O1–O1a	2.837(2)	C4–Zn1–O1a	130.00(10)

Symmetry code a: 1 – x, 1 – y, 1 – z.

Left: Molecular structure of [n class="Chemical">Zn2(BMdiPhIAEt)2Et2] iclass="Chemical">n the crystal. The class="Chemical">n class="Chemical">metal‐bound ethyl group is disordered, only the major disorder component is shown. Hydrogen atoms are omitted for clarity. Displacement ellipsoids are drawn at the 40 % probability level. Right: schematic representation of [Zn2(BMdiPhIAEt)2Et2], chiral centers are indicated with R and S.

Selected bond lengths and angles found in [n class="Chemical">Zn2(BMdiPhIAEt)2Et2]a

Upon the 1,2‐addition a new C–C bond is formed between the ethyl groups and the original n class="Chemical">carbonyl class="Chemical">n class="Chemical">carbons, resulting in two chiral carbon centers in [Zn2(BMdiPhIAEt)2Et2] (as indicated in Figure 2) and the reduction of the ketones to alkoxide groups. The resulting BMdiPhIAEt ligand coordinates in an asymmetric manner with only one of the imidazole nitrogen atoms coordinating to a zinc center. The central Zn2(µ‐O)2 planar core is similar to those found in previously reported complexes (vide infra), also the Zn···Zn distance of 2.9497(6) Å is similar to related compounds.28, 42, 43, 45 Only one example of a Zn‐alkoxide isolated from a 1,2‐addition to a ketone has been reported before in the literature (Scheme 1A).33

As mentioned before the n class="Chemical">Zn2(µ‐O)2 placlass="Chemical">nar core observed here is quite a commoclass="Chemical">n structural motif. The majority of structures coclass="Chemical">ntaiclass="Chemical">niclass="Chemical">ng this motif are obtaiclass="Chemical">ned from coordiclass="Chemical">natioclass="Chemical">n reactioclass="Chemical">ns of amiclass="Chemical">no alcohols with alkylziclass="Chemical">nc compouclass="Chemical">nds.35, 42, 43, 46, 47, 48, 49, 50, 51, 52, 53, 54 The formatioclass="Chemical">n of such a class="Chemical">n class="Chemical">Zn2O2‐motif is often thermodynamically favored, e.g. it also forms in the reaction of O2 with alkylzinc reagents and an external ligand; in the latter reaction O2 is activated leading to the selective oxygenation of one Zn–C bond.44, 55 Furthermore, complexes with a planar Zn2(µ‐O)2‐core are known to be active as initiator and catalyst in ring opening polymerization (ROP) reactions,47, 51, 56, 57, 58 and catalytically active in, e.g., enantioselective addition of dialkylzinc compounds to aldehydes59, 60 and the asymmetric alternating copolymerization of cyclohexene oxide or oxirane and CO2.52, 54, 61

NMR Spectroscopic Studies

The room temperature n class="Chemical">1H NMR spectrum of [class="Chemical">n class="Chemical">Zn2(BMdiPhIAEt)2Et2] shows rather broad signals, implying dynamic processes in solution on the NMR timescale. Recording the 1H NMR spectrum at –30 °C results in sharpening of the signals, leading to two well‐separated peaks at δ = 3.76 and 3.65 ppm, assigned to the N–CH 3 groups corresponding to an asymmetric coordination of the ligands (Figure S8, bottom). Additionally, the CCH 2CH3 signals appear as complex multiplets with an ABX3 pattern at δ = 3.03 and 2.89 ppm consistent with the chirality described for the crystal structure. A selective decoupling experiment by irradiating the signal for the CH3‐group results in a clean AB pattern at δ = 3.03 and 2.89 ppm with 2 J A,B = 13.3 Hz for the geminal protons (inset Figure S8). Also for the ZnCH 2CH3 groups an ABX3 pattern is observed and a similar decoupling experiment results in the corresponding AB pattern at δ = 0.58 and 0.53 ppm with 2 J A,B = 12.9 Hz (inset Figure S8). Using a decoupling experiment in which the signal of an ethyl CH2‐group is selectively irradiated, the overlapping C/Zn‐CH2CH 3 signals at 1.2 ppm could be distinguished. Accordingly, the triplet at δ = 1.23 ppm was assigned to ZnCH2CH 3 and the triplet at δ = 1.18 ppm was assigned to CCH2CH 3. These NMR spectroscopic data indicate that the geometry observed for [Zn2(BMdiPhIAEt)2Et2] in the solid state is retained in solution at low temperature (–30 °C). Recording the 1H NMR spectrum at 80 °C also results in a spectrum with sharp signals (Figures S7 and S8, top). In this spectrum only one peak for the four N–CH 3 substituents is observed at δ = 3.61 ppm, indicating a fast exchange of the coordinating and non‐coordinating imidazole rings which results in a fast inversion of configuration of the chiral carbon centers.

Analogous to the n class="Chemical">1H NMR spectra, the class="Chemical">n class="Chemical">13C NMR spectrum at room temperature only shows broad and very weak signals while the spectrum recorded at low temperature shows sharp signals. At –30 °C, two well separated signals for the N–CH3 groups are observed at δ = 33.9 and 33.2 ppm in accordance to the 1H NMR spectroscopic data. Moreover, the characteristic downfield signal for the carbonyl carbon found at δ = 176.5 ppm for BMdiPhIK is no longer present in the product. Instead, a new signal at δ = 79.9 ppm is found, which is assigned to the alkoxide carbon.

As shortly mentioned above, the zinc‐dimer [n class="Chemical">Zn2(BMdiPhIAEt)2Et2] was hydrolyzed with a saturated aqueous class="Chemical">n class="Chemical">NH4Cl solution. Subsequent extraction with CH2Cl2 yielded H‐BMdiPhIAEt in 89 % yield. 1H NMR analysis showed a pure product with a triplet at δ = 1.04 ppm and a quartet at δ = 2.75 ppm, indicating the ethyl‐substituent (Figure S12). One singlet at δ = 3.32 ppm accounting for two N–CH 3 groups shows that the product is symmetric on the bridging carbon. 13C NMR analysis confirmed the reduction of the carbonyl group, now showing a signal at δ = 72.8 ppm for the COH (Figure S13). There is no indication for the transfer of ethyl ligands to other parts of the ligand; consequently 1,4‐addition (N‐alkylation) could be excluded.

Mechanistic Studies

To investigate the reaction mechanism of the 1,2‐addition of n class="Chemical">Et2Zn to the class="Chemical">n class="Chemical">ketone in BMdiPhIK, the dark red intermediate (vide supra) was studied in more detail with NMR and EPR spectroscopy.

To be able to observe the n class="Chemical">reactive red iclass="Chemical">ntermediate species by NMR spectroscopy, the reactioclass="Chemical">n mixture obtaiclass="Chemical">ned from mixiclass="Chemical">ng class="Chemical">n class="Chemical">Et2Zn and BMdiPhIK at –95 °C in [D8]toluene was transferred to a pre‐cooled NMR tube and kept at –78 °C until it was transferred to the NMR spectrometer, which was pre‐cooled to –60 °C. The sample was still dark red when moved into the NMR spectrometer and it gave rather clean 1H and 13C NMR spectra (Figure S9 and Figure 3, top). The 1H NMR spectrum shows a quartet at δ = 0.32 ppm and a triplet at δ = 1.54 ppm assigned to the ethyl groups. The rather small shift compared to the authentic sample of Et2Zn in [D8]toluene at –60 °C, in which the signals appear at δ = 0.06 and 1.18 ppm (Figure S9, middle), indicates that both ethyl ligands are still bound to zinc. Furthermore, comparison to the 1H NMR spectrum of the free BMdiPhIK ligand also shows minor shifts only, implying coordination of the ligand to the zinc center but no reaction on the ligand backbone.

Figure 3

13C NMR spectra of [Zn(BMdiPhIK)Et2] (top) and the starting materials Et2Zn (middle) and BMdiPhIK (bottom) in [D8]toluene recorded at –60 °C. S indicates the residual solvent peak.

n class="Chemical">13C NMR spectra of [class="Chemical">n class="Chemical">Zn(BMdiPhIK)Et2] (top) and the starting materials Et2Zn (middle) and BMdiPhIK (bottom) in [D8]toluene recorded at –60 °C. S indicates the residual solvent peak.

In the n class="Chemical">13C NMR spectrum a dowclass="Chemical">nfield class="Chemical">n class="Chemical">carbonyl signal is visible at δ = 171.5 ppm (δ =176.5 ppm in the free ligand), showing that the carbonyl in this intermediate species is still present (Figure 3, top). Additionally, the BMdiPhIK methyl‐substituent and zinc‐bound ethyl ligands are observed at 5.48, 14.62, and 34.34 ppm, respectively. These NMR spectra support the idea that the dark red intermediate is the coordination compound [Zn(BMdiPhIK)Et2] as proposed in Scheme 2. This is in accordance with what was earlier proposed for similar reactions,28, 34 and the formation of this coordination compound is likely to be the first step in the reaction pathway towards the final Zn‐alkoxide product.

Upon warming the NMR cavity from –60 °C to –40 °C a reaction started to occur. Over a period of 50 minutes a n class="Chemical">1H NMR spectrum was recorded every 10 miclass="Chemical">n at –40 °C (Figure 4). Duriclass="Chemical">ng these 50 miclass="Chemical">nutes the iclass="Chemical">nteclass="Chemical">nsity of the [class="Chemical">n class="Chemical">Zn(BMdiPhIK)Et2] signals gradually decreased and the intensity of the [Zn2(BMdiPhIAEt)2Et2] signals increased while the sum of the two species stayed the same (Figure S6). No significant amounts of other species were observed during this time interval, which indicates that intermediate species have a very short lifetime or are NMR silent, as could be the case with radical intermediates. In contrast to what Lewinski et al. observed in the reaction of Et2Zn with dibenzoyl, there was no indication for the formation of aggregates in this reaction.28

Figure 4

1H NMR spectral changes during the course of the reaction of [Zn(BMdiPhIK)Et2] towards [Zn2(BMdiPhIAEt)2Et2] recorded at –40 °C in [D8]toluene. Increasing and decreasing signals upon progress of the reaction are shown with arrows.

n class="Chemical">1H NMR spectral chaclass="Chemical">nges duriclass="Chemical">ng the course of the reactioclass="Chemical">n of [class="Chemical">n class="Chemical">Zn(BMdiPhIK)Et2] towards [Zn2(BMdiPhIAEt)2Et2] recorded at –40 °C in [D8]toluene. Increasing and decreasing signals upon progress of the reaction are shown with arrows.

For the strongly related reactions of e.g. α‐diimines with n class="Chemical">alkylzinc reagents a SET class="Chemical">n class="Chemical">radical mechanism is proposed.41 However, the detection of any radical species with EPR spectroscopy during the course of the 1,2‐addition reaction of Et2Zn to BMdiPhIK at various temperatures going gradually from 100 K to room temperature was not successful. This indicates that either no radical species are involved in this reaction or, more likely, that the radical intermediates are short lived and therefore exist only at low steady‐state concentration, possibly reacting within the solvent cage.

In another attempt to determine the involvement of n class="Chemical">radical iclass="Chemical">ntermediates, a cold class="Chemical">n class="Chemical">toluene solution containing 10 equivalents of DMPO (5,5‐dimethyl‐1‐pyrroline‐N‐oxide) was added to a toluene solution of the dark red intermediate at –78 °C, this caused the mixture to turn colorless immediately without increasing the temperature. EPR analysis showed a signal with a g‐value of 2.006, that is split into 6 lines with hyperfine coupling constants of AN = 14.2 G and AH = 40.2 G (Figure 5). This is in excellent agreement with literature data for the DMPO‐ethyl radical.62 The presence of the DMPO‐ethyl radical shows that ethyl radicals are accessible from the reaction between Et2Zn and BMdiPhIK.

Figure 5

EPR spectrum of the reaction mixture of [Zn(BMdiPhIK)Et2] with DMPO, recorded in toluene at ambient temperature.

EPR spectrum of the reaction mixture of [n class="Chemical">Zn(BMdiPhIK)Et2] with class="Chemical">n class="Chemical">DMPO, recorded in toluene at ambient temperature.

However, the immediate disappearance of the red color upon the addition of the n class="Chemical">DMPO solutioclass="Chemical">n iclass="Chemical">ndicates that the class="Chemical">n class="Chemical">DMPO does not trap the radicals that are present in solution but rather initiates the formation of ethyl radicals from [Zn(BMdiPhIK)Et2]. The initiation of radical formation from Et2Zn by a radical trap is not unprecedented. TEMPO, a different radical trap, has been reported to react with Et2Zn to afford both [EtZn(TEMPO)] and [Zn(TEMPO)2] complexes along with ethane, ethylene, and TEMPOEt‐Et.43 Also, DMPO has been shown to react with Et2Zn to form DMPO‐Et radicals, albeit the reported reaction was performed in the presence of O2.63 In the blank experiment of Et2Zn with DMPO, i.e. in the absence of BMdiPhIK, the same spectrum was obtained albeit in much lower intensity. Based on the higher intensity of the EPR signal in presence of BMdiPhIK, it was concluded that the presence of the ligand does enhance the radical transfer of the ethyl ligand.

n class="Chemical">Based oclass="Chemical">n the experimeclass="Chemical">ntal data, the mechaclass="Chemical">nism as showclass="Chemical">n iclass="Chemical">n Figure 6 is proposed for the reactioclass="Chemical">n betweeclass="Chemical">n class="Chemical">n class="Chemical">Et2Zn and BMdiPhIK. Initially, the experimentally detected coordination complex [Zn(BMdiPhIK)Et2] forms, followed by the homolytic cleavage of the zinc–ethyl bond resulting in an ethyl‐radical and a radical on the carbonyl in the BMdiPhIK ligand. These radical intermediates could not be detected, but the DMPO experiment suggests that ethyl radicals can be generated from [Zn(BMdiPhIK)Et2]. The formed radical pair collapses within the solvent cage to form a C–C bond and transforms the carbonyl moiety in an alkoxide. Upon dimerization, to attain the tetrahedral geometry on the Zn‐centers, the zinc dimer [Zn2(BMdiPhIAEt)2Et2] is formed in which the formed alkoxide moieties bridge between two Zn centers and one ethyl ligand remains on each Zn‐center. The spin density in the radical intermediate would be mainly located on the carbonyl resulting in the recombination of the radical pair at this position. This is fully consistent with previous studies on the reductive chemistry of the BMdiPhIK ligand and the corresponding zinc chloride complex for which a very similar radical intermediate is proposed.40 The theoretical energies of formation of different reaction intermediates are indicated in Figure 6. The initial complexation of Et2Zn by the BMdiPhIK ligand was found to be slightly endothermic by 7.5 kcal/mol, which appears inconsistent with the quantitative reaction observed experimentally. This is tentatively ascribed to solvent effects. The second step, i.e. the rate‐limiting formation of the radical pair, is associated with a ΔH of 22.1 kcal/mol starting from the complex. These steps are followed by two more strongly exothermic bond‐forming steps with ΔH of –32.0 and –26.4 kcal/mol, respectively, which are probably the driving forces in this reaction.

Figure 6

Energy diagram of the proposed radical reaction pathway for the 1,2‐addition of Et2Zn to the BMdiPhIK ketone ligand. Using the UBP86/6‐31g* (C, H, N, and O) and LANL2DZ (Zn) DFT computational level. Transition states are not calculated; accordingly, the dotted connections between the intermediates do not indicate the energies of the transition states.

Energy diagram of the proposed n class="Chemical">radical reactioclass="Chemical">n pathway for the 1,2‐additioclass="Chemical">n of class="Chemical">n class="Chemical">Et2Zn to the BMdiPhIK ketone ligand. Using the UBP86/6‐31g* (C, H, N, and O) and LANL2DZ (Zn) DFT computational level. Transition states are not calculated; accordingly, the dotted connections between the intermediates do not indicate the energies of the transition states.

Conclusions

Here, the addition of n class="Chemical">Et2Zn to the class="Chemical">n class="Chemical">ketone in the BMdiPhIK ligand was shown to take place in a very selective manner. In contrast to reactions of α‐diimines or α‐iminoketones with Et2Zn,34, 36 selective 1,2‐addition was found to occur and no N‐alkylation (1,4‐addition) was observed. The final product was isolated and fully characterized as a C‐alkylated binuclear zinc complex containing a planar centrosymmetric Zn2(µ‐O)2‐motif.

Knowing from previous studies that n class="Chemical">BMdiPhIK caclass="Chemical">n form rather stable class="Chemical">n class="Chemical">radicals upon reduction,40 this ligand was used to investigate the accessibility of a radical pathway for the alkylation of ketones. Although a polar mechanism cannot be excluded based on the experimental data shown here, the current study indicates the viability of a radical pathway. No radical intermediates have been detected, however the accessibility of ethyl‐radicals was shown using DMPO as a radical trap. It is proposed that the radical intermediates recombine within the solvent cage, hampering their detection. The initially formed coordination compound, [Zn(BMdiPhIK)Et2], that precedes ethyl‐transfer, has been successfully characterized using low temperature NMR experiments. Additionally, DFT calculations confirmed the plausibility of the proposed radical pathway.

It is of interest to investigate the reactivity of n class="Chemical">BMdiPhIK with other class="Chemical">n class="Chemical">alkylzinc reagents to see if this would allow the detection of more stable radical intermediates. Additionally, the ability to transfer the alkyl ligand to external reagents and to use catalytic amounts of BMdiPhIK would be of interest.

Experimental Section

All air‐sensitive organic reactions, as well as the handling and synthesis of n class="Chemical">diethylzinc reageclass="Chemical">nts, were carried out uclass="Chemical">nder aclass="Chemical">n iclass="Chemical">nert atmosphere of dry aclass="Chemical">nd class="Chemical">n class="Chemical">oxygen‐free N2 using standard Schlenk techniques or were handled in an MBraun labmaster dp glovebox workstation. [D2]CH2Cl2 was dried with CaH2 and distilled under N2 atmosphere prior to use. THF was distilled from sodium/benzophenone before use, distilled under N2. Dry toluene and hexane were obtained from an mBraun MB SPS‐800 solvent purification system and stored over 3 Å molecular sieves. [D8]Toluene was dried with 3 Å molecular sieves. Solvents were degassed by bubbling N2 through for ±30 min or by freeze‐pump‐thaw degassing prior to use. 1H and 13C{1H}, and 1H‐13C HSQC NMR spectra were recorded at 298 K on a Varian VNMRS400 or an Oxford NMR AS400 spectrometer at 400 MHz and 100 MHz, respectively. Chemical shifts are reported in ppm with respect to tetra methylsilane (TMS) based on the position of residual solvent peaks as reported by Fulmer et al.64 ATR infrared spectra were recorded on a Perkin–Elmer Spectrum One FTIR spectrometer. ESI‐MS spectra were recorded on a Waters LCT Premier XE KE317 Micromass Technologies spectrometer. Elemental microanalyses were carried out by the Mikroanalytischen Laboratorium Kolbe, Mulheim a.d. Ruhr, Germany. BMdiPhIK is synthesized according to literature procedure.40 All other chemicals were commercially obtained and used as received. Caution: Et2Zn used in the reactions described below are pyrophoric compounds reacting violently with oxygen and water. Special care must be taken when operating with these compounds.

[n class="Chemical">Zn(BM class="Chemical">n class="Chemical">Diethylzinc (1.0 m in [D8]toluene, 0.10 mL, 0.10 mmol) was added to a frozen suspension of BMdiPhIK (50 mg, 0.10 mmol) in [D8]toluene (2 mL) at –196 °C upon which the added drops froze instantaneously. The mixture was slowly melted, resulting in a clear dark red solution, which was transferred to an NMR tube and kept at –78 °C and transferred, as a dark red sample, to the pre‐cooled NMR spectrometer at –60 °C. 1H NMR (400 MHz, [D8]toluene, –60 °C): δ = 7.84 (d, 3 J H,H = 7.6 Hz, 4 H, o‐PhH), 7.15 (m, 6 H, PhH), 6.95 (m, 6 H, PhH), 6.75 (d, 3 J H,H = 6.5 Hz, 4 H, o‐PhH), 3.34 (s, 6 H, NCH 3), 1.54 (t, 3 J H,H = 7.7 Hz, 6 H, ZnCH2CH 3), 0.32 (q, 3 J H,H = 7.7 Hz, 4 H, ZnCH 2CH3) ppm. 13C NMR (101 MHz, [D8]toluene, –60 °C): δ = 171.5, 141.3, 141.0, 135.8, 132.4, 130.9, 129.3, 128.9, 128.5, 128.3, 34.3, 14.6, 5.5 ppm (two signals are overlapping with residual toluene signals).

[n class="Chemical">Zn class="Chemical">n class="Chemical">Diethylzinc (1.0 m in hexanes, 0.40 mL, 0.40 mmol) was added dropwise to a suspension of BMdiPhIK (199 mg, 0.402 mmol) in toluene (10 mL) at –78 °C to yield a dark red solution. During stirring for 1 h the reaction mixture stays dark red. The solution was warmed to room temperature for 1 h during which the mixture turns clear and colorless. Afterwards all volatiles were removed in vacuo to yield the crude product as a white powder, which was purified by crystallization from THF by slow vapor diffusion of hexanes (175 mg, 71 %). C74H72N8O2Zn2 (1232.44): calcd. C 71.90, H 5.87, N 9.06; found C 72.11, H 6.03, N 8.97. 1H NMR (400 MHz, [D8]toluene, –30 °C): δ = 7.74 (d, 3 J H,H = 7.8 Hz, 4 H, o‐PhH), 7.70 (d, 3 J H,H = 7.5 Hz, 4 H, o‐PhH), 7.25 (“d”, 3 J H,H = 4.7 Hz, 4 H, o‐PhH), 7.12 (s, 3 H), 7.06–6.89 (m, 21 H), 6.84 (d, 3 J H,H = 7.1 Hz, 4 H, o‐PhH), 3.76 (s, 6 H, NCH 3), 3.65 (s, 6 H, NCH 3), 3.03 [ABX3, 2 J H,H = 13.3 Hz, 2 H, C(O)CH 2CH3], 2.89 [ABX3, 2 J H,H = 13.3 Hz, 2 H, C(O)CH 2CH3], 1.23 (t, 3 J H,H = 8.0 Hz, 6 H, ZnCH2CH 3), 1.18 [t, 3 J H,H = 7.2 Hz, 6 H, C(O)CH2CH 3], 0.58 (ABX3, 2 J H,H = 12.9 Hz, 2 H, ZnCH 2CH3), 0.53 (ABX3, 2 J H,H = 12.9 Hz, 2 H, ZnCH 2CH3) ppm. 13C NMR (101 MHz, [D8]toluene, –30 °C): δ = 157.8, 150.0, 136.1, 135.9, 133.8, 133.6, 132.0, 131.8, 131.4, 131.2, 129.9, 129.8, 128.9, 128.2, 128.0, 127.3, 126.0, 79.9, 35.7, 33.9, 33.2, 12.8, 9.0, 2.3 ppm (some signals are overlapping with the toluene signals). IR (ATR): ν̃ = 3054.3 (w), 3032.6 (w), 3005.1 (w), 2971.3 (w), 2929.2 (w), 2882.5 (w), 2844.0 (w), 1602.0 (m), 1504.2 (m), 1465.9 (m), 1443.1 (m), 1394.2 (m), 1386.2 (m), 1326.6 (w), 1290.0 (w), 1245.9 (w), 1232.0 (w), 1170.0 (w), 1134.2 (m), 1079.4 (m), 1070.4 (m), 1025.0 (m), 981.42 (m), 916.9 (m), 889.5 (m), 774.75 (s), 749.57 (m), 695.72 (s), 600.75 (m), 544.35 (m), 506.1 (m) cm–1. ESI‐MS (THF/CH2Cl2/formic acid): m/z = 1111.4349 [Zn(BMdiPhIAEt)2 – H+]+, calcd. 1111.4365, 1207.3925 [Zn2(BMdiPhIAEt)2Et2 – Et–]+, calcd. 1207.3948. X‐ray crystal structure determination: C74H72N8O2Zn2, Fw = 1236.13, colorless plate, 0.19 × 0.12 × 0.03 mm3, monoclinic, P21/c (no. 14), a = 13.2084(6), b = 17.9543(6), c = 13.4432(6) Å, β = 107.174(2)°, V = 3045.9(2) Å3, Z = 2, D= 1.348 g/cm3, µ = 0.84 mm–1. 42520 Reflections were measured on a Bruker Kappa ApexII diffractometer with sealed tube and Triumph monochromator (λ = 0.71073 Å) at a temperature of 150(2) K up to a resolution of (sin θ/λ)max = 0.65 Å–1. The Eval15 software65 was used for the integration of the intensities. Multiscan absorption correction and scaling was performed with SADABS66 (correction range 0.60–0.75). 6990 Reflections were unique (R = 0.052), of which 4883 were observed [I > 2σ(I)]. The structure was solved with Patterson superposition methods using SHELXT.67 Least‐squares refinement was performed with SHELXL‐201468 against F 2 of all reflections. Non‐hydrogen atoms were refined freely with anisotropic displacement parameters. The metal‐bound ethyl group was refined with a disorder model (occupancy 0.8:0.2). Hydrogen atoms were introduced in calculated positions and refined with a riding model. 397 Parameters were refined with 2 restraints (distances and angles in the disordered moiety). R1/wR2 [I > 2σ(I)]: 0.0432/0.1008. R1/wR2 [all refl.]: 0.0750/0.1145. S = 1.031. Residual electron density between –0.33 and 0.51 e/Å3. Geometry calculations and checking for higher symmetry were performed with the PLATON program.69

https://www.ccdc.cam.ac.uk/services/structures?id=doi:10.1002/ejic.201701363 1582913 {for [n class="Chemical">Zn2(BMdiPhIAEt)2Et2]} coclass="Chemical">ntaiclass="Chemical">ns the supplemeclass="Chemical">ntary crystallographic data for this paper. These data caclass="Chemical">n be obtaiclass="Chemical">ned free of charge from http://www.ccdc.cam.ac.uk/.

H‐BM [n class="Chemical">Zn2(BMdiPhIAEt)2Et2] (58.5 mg, 0.0473 mmol) was hydrolyzed by the additioclass="Chemical">n of a saturated class="Chemical">n class="Chemical">NH4Cl solution (5 mL). The obtained suspension was extracted with CH2Cl2 (3 × 10 mL). The yellow organic layers were collected and dried with MgSO4, filtered and all volatiles were removed in vacuo yielding the product as yellow solid (44.4 mg, 89 %). 1H NMR (400 MHz, [D8]toluene, –30 °C): δ = 7.50–7.43 (m, 10 H, PhH), 7.33–7.31 (m, 4 H, PhH), 7.23–7.19 (m, 4 H, PhH), 7.16–7.12 (m, 2 H, PhH), 5.82 (s, 1 H, OH), 3.32 (s, 6 H, NCH 3), 2.75 [q, 3 J H,H = 7.4 Hz, 2 H, C(OH)CH 2CH3], 1.04 [t, 3 J H,H = 7.4 Hz, 3 H, C(OH)CH2CH 3] ppm. 13C NMR (101 MHz, [D]chloroform1, 25 °C): δ = 147.5, 135.3, 134.6, 131.3, 131.1, 130.7, 129.1, 128.9, 128.3, 126.8, 126.4, 72.8, 32.1, 31.9, 7.7 ppm. IR (ATR): ν̃ = 3405.2 (br., w), 3056.5 (w), 3029.0 (w), 2961.2 (w), 2937.4 (w), 1602.8 (m), 1505.5 (m), 1443.0 (m), 1386.8 (m), 1356.0 (m), 1320.8 (m), 1231.7 (w), 1179.0 (w), 1134.6 (m), 1072.3 (m), 1025.0 (m), 967.33 (m), 917.55 (w), 841.25 (w), 774.07 (s), 747.7 (w), 696.16 (s), 649.62 (w), 544.11 (m) cm–1. ESI‐MS (THF/CH2Cl2/formic acid): m/z = 525.2654 [(H‐BMdiPhIAEt) + H+]+, calcd. 525.2654.

n class="Chemical">Radical Trappiclass="Chemical">ng with class="Chemical">n class="Chemical">DMPO: Diethylzinc (1.0 m in toluene, 0.10 mL, 0.10 mmol) was added dropwise to a yellow suspension of BMdiPhIK (50 mg, 0.10 mmol) in toluene (10 mL) at –78 °C to yield a dark red solution. A part of this dark red solution (0.15 mL) is transferred to a cold EPR tube and a cold solution containing 10 equiv. of DMPO (0.1 m in toluene, 0.15 mL) is added upon which the red color immediately disappeared resulting in a colorless solution.

Computational Details: DFT results were obtained using the Gaussian 09 software package,70 using the n class="Chemical">UBP86 fuclass="Chemical">nctioclass="Chemical">nal aclass="Chemical">nd the 6‐31g* basis set oclass="Chemical">n C, H, N, aclass="Chemical">nd O aclass="Chemical">nd LANL2DZ oclass="Chemical">n class="Chemical">n class="Chemical">Zn. Frequency analyses were performed on all calculations.

Supporting Information

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