Mechanisms of Reactions of a Lithium Boryl with Organohalides

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Mechanisms of Reactions of a Lithium Boryl with Organohalides Man Sing Cheung,† Todd B. Marder,*,‡ and Zhenyang Lin*,† † ‡

Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, U.K.

bS Supporting Information ABSTRACT: Reactions of the lithium boryl LiB(R0 NCHd CHNR0 ) (R0 = 2,6-iPr2C6H3), 1, with organohalides (RX) giving RB(R0 NCHdCHNR0 ) and/or XB(R0 NCHdCHNR0 ) were studied computationally using density functional theory calculations at the B3LYP level. Our calculations indicate that the boryl anion in the lithium boryl can undergo nucleophilic attack at an organohalide on the halide-bonded carbon atom and/or the halogen atom to form RB(MeNCHdCHNMe) (an expected SN2 substitution product) and/or XB(MeNCHdCHNMe) (a halogen-abstraction product), respectively. Our energetic calculation results show that an organohalide having a halogen with lower electronegativity and higher ability to engage in hypervalent bonding promotes the halogen-abstraction pathway. Benzyl halides were also found to promote the halogenabstraction pathway due to conjugation effects that stabilize a benzyl anion in the transition state during the halogen-abstraction process.

’ INTRODUCTION Transition metal boryl complexes1 play an important role as active intermediates in many catalytic reactions including metalcatalyzed hydroboration,2,3 diboration,4
10 dehydrogenativeborylation,3a,11 and other boron additions to unsaturated organic compounds,12 as well as borylation of carbon
halogen bonds in arenes,13 heteroarenes,13b,d,f,j,14 and alkenes,15 and direct borylation of C
H bonds.16
20 Over the past few years, extensive theoretical and experimental studies have shown that the boryl ligands in transition metal complexes, in spite of having a three-coordinate center, exert an extremely strong trans influence and display highly nucleophilic behavior in the catalytic reactions.9b,d,10,21,22 In 2006, Segawa et al. reported the isolation of the first structurally characterized lithium boryl compound, LiB(R0 NCHdCHNR0 ) (R0 = 2,6-iPr2C6H3), 1, a main group metal boryl compound in which the B
Li bond is highly polarized and the boron center shows anionic character.23,24b Boryl compounds of Mg2þ and Zn2þ have also recently been synthesized and structurally characterized.24 Reactivity studies of these main group metal boryl compounds show that the boryl anions react with a variety of electrophiles, displaying their nucleophilicity as expected. Interestingly, these studies indicate that the boryl anions also show halophilic behavior. Experimentally, it was found that when the lithium boryl 1 reacted with organohalides RX, nucleophilic substitution to give RB(R0 NCHdCHNR0 ) and/or halogen abstraction to give XB(R0 NCHdCHNR0 ) was observed. Scheme 1 shows the interesting experimental results observed for the reactions of the lithium boryl 1 with a few representative organohalides RX.24b Products 2 are those expected when nucleophilic substitution occurs, while 3 are formed when halogen abstraction takes place. The experimental results are interesting. In this paper, we explore in detail the r 2011 American Chemical Society

chemoselectivity observed in the reactions by employing density functional theory (DFT) calculations, in order to understand how different organohalides affect the outcome of reactions with boryl anions.

’ COMPUTATIONAL DETAILS Molecular geometries were optimized at the Becke3LYP (B3LYP) level of density functional theory.25 The effective core potentials (ECPs) of Hay and Wadt with the double-ζ valence basis sets (LanL2DZ)26 were used to describe Cl, Br, and I atoms. The 6-311G* Pople basis set27 was used for Li, B, and those C atoms involved in the bond-breaking and -making processes. The standard 6-31G basis set28 was used for all other atoms. Polarization functions were added for Cl(ζd = 0.640), Br(ζd = 0.428), and I(ζd = 0.289).29 Frequency calculations were carried out to confirm the characteristics of all of the optimized structures as minima (zero imaginary frequency) or transition states (one imaginary frequency) and to provide free energies at 298.15 K, which include entropy contributions. Calculations of intrinsic reaction coordinates (IRC)30 were also performed to confirm that the transition states connect two relevant minima. All of the calculations were performed with the Gaussian 03 software package.31 The natural bond orbital (NBO) program,32 as implemented in Gaussian 03, was also used to perform charge population analyses.33 To consider solvent effects, we also employed a continuum medium to do single-point calculations for all species, using Bondi’s atomic radii (RADII=BONDI) based on the polarizable continuum model (PCM).34 Tetrahydrofuran was used as solvent, corresponding to the experimental conditions. To examine whether the inclusion of continuum solvation may distort the results somewhat, we performed geometry optimizations for several Received: February 7, 2011 Published: May 09, 2011 3018

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especially for geometry optimization calculations.36 The results show that the effect is very small. For example, for the reaction of 1 with CH3Cl, the transition states TSA and TSB lie above 1 þ CH3Cl by 17.4 and 19.8 kcal/mol, respectively, with the single-point calculations, and by 18.2 and 19.2 kcal/mol, respectively, with the solvated optimization calculations. For the reaction of 1 with CH3Br, the transition states TSA and TSB lie above 1 þ CH3Br by 14.1 and 10.6 kcal/mol, respectively, with the single-point calculations, and by 14.1 and 10.0 kcal/mol, respectively, with

selected species using the UAKS radii on the conductor-like polarizable continuum model.35 This solvation method was found to be efficient

Scheme 1

Figure 2. Simplified version of the solvation-corrected free energy (kcal/mol) profiles calculated for reactions of the lithium boryl 1 with different organohalides showing the energetics related only to the reactants, transition states, and the products: (a) 1 þ CH3Cl, (b) 1 þ PhCH2Cl, (c) 1 þ CH3Br, (d) 1 þ PhCH2Br, (e) 1 þ CH3I, (f) 1 þ PhCH2I.

Figure 1. Schematic free energy profiles for the reaction of the lithium boryl with organohalides.

Table 1. Solvation-Corrected and Gas-Phase Relative Free Energies (kcal/mol), ΔGsolv and ΔGgas (in parentheses), Calculated for the Species Involved in the Two Reaction Pathways Shown in Figure 1 RX

CH3Cl

CH3Br

CH3I

PhCH2Cl

PhCH2Br

PhCH2I

1 þ RX

0.0 (0.0)

0.0 (0.0)

0.0 (0.0)

0.0 (0.0)

0.0 (0.0)

0.0 (0.0)

vdWA TSA

7.9 (4.9) 17.4 (18.6)

8.4 (5.4) 14.1 (14.4)

9.8 (6.8) 11.4 (11.0)

9.6 (5.1) 19.4 (19.5)

10.8 (6.3) 16.2 (15.5)

11.7 (7.1) 15.1 (13.1)

2þ4


104.9 (
98.9)


104.8 (
99.3)


102.5 (
98.0)


99.6 (
93.6)


99.6 (
94.1)


97.5 (
93.1)

vdWB

6.7 (5.9)

11.0 (8.9)

5.6 (3.3)

11.4 (9.7)

12.4 (11.1)

11.5 (9.7)

19.8 (19.4)

10.6 (11.8)

7.2 (7.6)

13.9 (11.3)

12.4 (11.1)a

11.5 (9.7)a

vdWB1


33.9 (
35.1)


27.8 (
29.1)


21.6 (
22.9)


40.9 (
44.3)


36.9 (
39.8)


30.7 (
33.8)

3þ5


45.6 (
44.2)


40.8 (
39.2)


35.7 (
34.0)


49.0 (
49.6)


44.2 (
44.7)


39.4 (
39.8)

TSB

a

The transition-state structures TSB in these cases are almost the same as the van der Waals complexes vdWB. In other words, the vdWB f vdWB1 step is almost barrierless. The corresponding transition state cannot be located computationally, and vdWB is taken as the approximate transition state. 3019

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Figure 3. Transition-state structures calculated for the 12 pathways shown in Figure 2. Selected bond distances are given in Å. Hydrogen atoms associated with the model boryl anions and the two lithium-coordinated thf molecules are omitted for clarity. The van der Waals complexes vdWBBzBr and vdWBBzI were approximately considered as the transition-state structures TSBBzBr and TSBBzI, respectively, in view of the almost barrierless vdWB f vdWB1 transformation in these two cases. the solvated optimization calculations. The gas-phase and solution-phase optimized geometries also do not differ much (see Supporting Information). The impact of solvation effects on classical SN2 reactions of RX þ Y
f RY þ X
when treated in the gas phase is well documented.37 The very small effect found in this work is presumably related to the fact that the systems studied here are all neutral; that is, the countercation Liþ is involved in the reactions and was included in the calculations.

’ RESULTS AND DISCUSSION Our study addresses the chemoselectivity of the reactions of a boryl anion with various organohalides, as depicted in Scheme 1. For simplicity in our DFT calculations, we employed CH3X and PhCH2X (X = Cl, Br, and I) as representative alkyl- and benzylhalides, respectively. The lithium boryl 1 was modeled 3020

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Table 2. Partial Charges Calculated for the Boryl Anion, the Li(thf)2 Fragment, R, and X in the Reactants (1 þ RX), Transition States (TSA for Pathway A and TSB for Pathway B), and Products (2 þ 4 for Pathway A and 3 þ 5 for Pathway B) in the 12 Pathways Shown in Figure 2 pathway A

pathway B

state

boryl

Li(thf)2

R

X

boryl

Li(thf)2

R

X

reactant


0.358

þ0.358

þ0.129


0.129


0.358

þ0.358

þ0.129


0.129

TS


0.222

þ0.444

þ0.158


0.381


0.065

þ0.559


0.139


0.354

product

þ0.282

þ0.523


0.282


0.523

þ0.213

þ1.044


1.044


0.213

reactant


0.358

þ0.358

þ0.129


0.129


0.358

þ0.358

þ0.129


0.129

TS product


0.235 þ0.302

þ0.423 þ0.523

þ0.193
0.302


0.381
0.523


0.340 þ0.213

þ0.420 þ0.646

þ0.030
0.646


0.109
0.213

reactant


0.358

þ0.358

þ0.122


0.122


0.358

þ0.358

þ0.122


0.122

TS


0.222

þ0.443

þ0.138


0.360


0.048

þ0.638


0.491


0.099

product

þ0.282

þ0.570


0.282


0.570

þ0.266

þ1.044


1.044


0.266

reactant


0.358

þ0.358

þ0.135


0.135


0.358

þ0.358

þ0.135


0.135

TS


0.235

þ0.422

þ0.179


0.367


0.358

þ0.332

þ0.116


0.090

product

þ0.302

þ0.570


0.302


0.570

þ0.266

þ0.646


0.646


0.266

CH3I

reactant TS


0.358
0.209

þ0.358 þ0.450

þ0.030 þ0.068


0.030
0.309


0.358
0.167

þ0.358 þ0.683

þ0.030
0.513


0.030
0.003

product

þ0.282

þ0.615


0.282


0.615

þ0.260

þ1.044


1.044


0.260

PhCH2I

reactant


0.358

þ0.358

þ0.053


0.053


0.358

þ0.358

þ0.053


0.053

TS


0.238

þ0.429

þ0.129


0.320


0.347

þ0.356

þ0.012


0.021

product

þ0.302

þ0.615


0.302


0.615

þ0.260

þ0.646


0.646


0.260

RX CH3Cl

PhCH2Cl

CH3Br

PhCH2Br

by (thf)2LiB(MeNCHdCHNMe) (thf = tetrahydrofuran) in which the bulky 2,6-iPr2C6H3 substituents at each N of the experimental boryl anion were replaced by Me. Introduction of two thf ligands on lithium is based on the structure of 1 observed by single-crystal X-ray diffraction.38 Figure 1 shows two pathways we calculated for the reaction of the lithium boryl with an organohalide. In pathway A, the boryl anion acts as a nucleophile, substituting the halide of the organohalide to give the RB(MeNCHdCHNMe) product 2 via a van der Waals complex (vdWA) through an SN2-type transition state (TSA).24b In pathway B, halogen abstraction occurs to give the XB(MeNCHdCHNMe) product 3. Thus, the halogen can serve as the electrophilic center instead of the carbon, as we encounter traditionally. More discussion on this aspect will be given later. Table 1 summarizes the energetics calculated based on both pathways A and B for the reactions of the model lithium boryl compound 1 with the chosen representative organohalides. In order to visualize the trends in the thermodynamics and kinetics obtained for the reactions of the six representative organohalides, we provide a simplified version of the free energy profiles in Figure 2, showing the energetics related only to the reactants, transition states, and products. Analyzing the free energy profiles in Figure 2, we found that the reactions of 1 with the six representative organohalides are all highly exergonic no matter which pathway is considered. In all of the cases, pathway A is more exogonic than pathway B (ca.
100 kcal/mol versus ca.
40 kcal/mol). Due to the fact that both pathways (A and B) are highly exergonic, reversibility of the reactions can be excluded. Therefore, the products arise from a reaction under kinetic control. From Figure 2, we can see that the organochlorides have the largest reaction barriers, while the organoiodides have the smallest barriers, consistent with the trend in the R
X bond strength.

For the reactions of CH3X, pathway A is kinetically favored over pathway B when X = Cl (Figure 2a). However, when X = Br or I, pathway B is preferred kinetically (Figure 2c,e). For the reactions of PhCH2X, pathway B is always kinetically favored over pathway A, no matter which halogen (X = Cl, Br, or I) is present (Figure 2b,d,f). These results are consistent with the experimental observations that only the reaction of nBuCl gave 2 as the major product, while the reactions of PhCH2Cl, nBuBr, and PhCH2Br gave 3 as the major product.24b Figure 3 shows the transition-state structures with selected bond distances calculated for the reactions of 1 with the six organohalides RX, and Table 2 shows the partial charges of the boryl anion, the Li(thf)2 fragment, R, and X calculated for reactants, transition states, and products in the above-mentioned two pathways for each reaction. Figure 3 clearly shows that the structures of TSA correspond to SN2 transition states in which the boryl anion acts as the nucleophile and the halides as the leaving groups. In each of the transition-state structures of TSB, the boryl anion, the halide, and the alkyl group are almost collinear. Transition-state structures having similar structural features were previously proposed to account for chlorination of arene C
H bonds with protonated chloroamines.39 The collinear structural feature in the transitionstate structures has the following important implication. The halogen-abstraction pathway can also be viewed as an SN2 reaction in which the boryl anion acts as the nucleophile attacking a halogen center, while the alkyl, not the halide, acts as the leaving group. In transition states TSB, the halogen atom is hypervalent, which is more accessible for Br and I than for Cl. This explains why, for the reactions of 1 with RBr and RI, pathway B is always preferred over pathway A (Figure 2c,d,e,f) regardless of whether R = Me or PhCH2. In the reaction of 1 with CH3Cl, the halogenabstraction pathway is less favored kinetically (Figure 2a), apparently due to the relative difficulty of Cl to engage in hypervalent 3021

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Figure 5. σ*C
X orbitals calculated for CH3Cl, CH3Br, and CH3I.

Figure 4. Simplified version of the solvation-corrected free energy (kcal/mol) profiles calculated for the reaction of the model organolithium (thf)2LiCH3 with (a) CH3Cl, (b) CH3Br, and (c) CH3I via the pathways of a normal SN2 reaction (pathway A) and a halogen abstraction (pathway B), which show the energetics related only to the reactants, transition states, and the products.

bonding. Unexpectedly, in the reaction of 1 with PhCH2Cl, the halogen-abstraction pathway is favored (Figure 2b) despite the relative difficulty of Cl being hypervalent. Apparently, the phenyl ring in the PhCH2 moiety helps delocalize the negative charge accumulated on the benzyl chloride moiety during the nucleophilic attack on the chlorine atom by the boryl anion. The changes in the partial charges of the boryl anion, the Li(thf)2 fragment, R, and X from reactants, to the transition

states, and then to the products, given in Table 2, are consistent with the arguments given above. The partial charge associated with the boryl anion in general changes from negative to positive gradually throughout the reaction, consistent with the notion that it acts as nucleophile and that boron is less electronegative than either carbon or, of course, halogen. In pathway A, the partial charge on R first becomes slightly more positive in the transition state, favoring the nucleophilic attack by the boryl anion, and then is negative in the final product RB(MeNCHdCHNMe). On the other hand, the partial charge on X becomes progressively more negative. In pathway B, except for the CH3Cl case, the already negative partial charge on X becomes slightly less negative in the transition state and finally is more negative in the product XB(MeNCHdCHNMe). Clearly, the charge associated with X needs to become less negative in the transition state for pathway B in order to accommodate the incoming boryl anion. Br and I are less electronegative than Cl and can thus accommodate the required change more easily. For the reaction of CH3Cl, it is difficult to reduce the negative charge on the highly electronegative Cl. Therefore, pathway A is preferred in this case. In the case of PhCH2Cl, the phenyl group is able to delocalize the buildup of negative charge in the transition state, making the required change in the partial charge of Cl (from
0.129 to
0.109, Table 2) possible and pathway B favorable. In SN2 reactions of organohalides, nucleophiles typically attack the electropositive carbon center, causing an inversion in the configuration at this center. The examples studied here suggest that a boryl anion, with its highly nucleophilic nature,10,21,40 attacks preferentially the halogen atom, instead of the carbon center, of an organobromide or organoiodide. To compare the relative ease of the two pathways (a halogenabstraction and a normal SN2 reaction) with a carbon nuclophile, we carried out calculations on the model reaction of (thf)2LiCH3 with CH3X. For simplicity, we employed the two pathways shown in Figure 1 by simply replacing the boryl anion with a methyl anion in the calculations. Figure 4 shows a brief version of the free energy profile calculated for the model reaction. Figure 4 shows that for CH3Cl and CH3Br, the halogenabstraction pathway (pathway B) is unfavorable both kinetically and thermodynamically. For CH3I, kinetically both pathways have similar activation energies, but pathway A is thermodynamically favorable. The results are as expected, as the CH3
carbanion in methyllithium is much less nucleophilic when compared to the boryl anion in 1. We notice that the products derived from the halogen abstraction are the same as the 3022

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Organometallics Scheme 2

Figure 6. Solvation-corrected relative free energies (ΔGsolv, kcal/mol) calculated for the species involved in the reaction between 1 and a benzyl radical.

reactants. When carbon nucleophiles are considered, the products and reactants are similar in their bond types in the halogenabstraction pathway (RX þ LiR0 f R0 X þ LiR). Therefore, there is no thermodynamic driving force for a halogen abstraction to occur when a carbon nucleophile is considered. In contrast, a normal SN2 reaction with a carbon nucleophile (pathway A) leads to formation of a new strong carbon
carbon bond and the LiX salt, providing the necessary thermodynamic driving force. For the specific reaction of methyllithium with CH3I, pathway B would be reversible because of the degeneracy of the reaction. Therefore, in practice, we would not be able to observe such an abstraction pathway because there exists the thermodynamically favorable pathway A. From Figures 2 and 4, we can see that, for a given organohalide, halogen abstraction by the boryl anion is both kinetically and thermodynamically more favorable than that by the CH3
carbanion. The high nucleophilicity of the boryl anion promotes the abstraction kinetically.10,21,40 The strong B
X bond due to its high bond polarity stabilizes the abstraction product 3, making the abstraction thermodynamically favorable.41 In many reported halophilic (X-philic) reactions of nucleophiles with organohalides,42,43 certain halophilic nucleophiles attack the halogens of organohalides. These halophilic reactions are also closely related to the ability of the halogens in organohalides to engage in hypervalent bonding. An alternative explanation to the hypervalency argument for the halophilic reactions is based on the contribution of ψx to σ*C
X of the organohalides.42 The larger the contribution of ψx to σ*C
X,

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Scheme 3

the more X-philic reactions will be facilitated. Figure 5 shows plots of σ*C
X that we calculated for CH3Cl, CH3Br, and CH3I.44 In Figure 5, the contribution of ψx to σ*C
X is the largest when X = I and the smallest when X = Cl. In addition to the hypervalency argument given above, this molecular orbitalbased explanation also shows why halogen abstraction by the boryl anion occurs for CH3Br and CH3I, but not for CH3Cl. Reactions of benzyl halides often involve a radical mechanism.45b Therefore, one may argue that the reactions between 1 and PhCH2X might proceed by a radical mechanism. The commonly accepted radical mechanism for nucleophilic substitution reactions is the unimolecular radical nucleophilic substitution mechanism (SRN1), a chain process involving radicals and radical anions as intermediates.45 A possible SRN1 mechanism for the reaction between 1 and PhCH2X is shown in Scheme 2. The initiation of this chain mechanism could be achieved by a single electron transfer (SET) from 1 to PhCH2X to form a radical anion (eq 1). Once initiated, the radical anion dissociates to form a benzyl radical and a halide anion (eq 2). Then the benzyl radical is attacked by the boryl anion in 1 to form the corresponding benzylboryl radical anion (eq 3). Propagation is achieved by another PhCH2X molecule accepting one electron from the benzylboryl radical anion to form a new PhCH2 X radical anion (eq 4). On the basis of the SRN1 mechanism, one would expect only the PhCH 2B(MeNCHdCHNMe) product to be formed, inconsistent with the experimental observation. We calculated the energetics associated with eq 3 (Figure 6). The barrier for eq 3 is only 11.6 kcal/mol. This result suggests that a benzyl radical can easily induce the formation of the benzylboryl radical anion and facilitate the SRN1 mechanism. Experimentally, reaction of 1 with PhCH2Cl gives PhCH2B(RNCHdCHNR) as a minor product. In the reaction of 1 with PhCH2Br, PhCH2B(RNCHdCHNR) is not observed. These experimental observations clearly imply that benzyl radicals are not present under the experimental conditions reported, and the SRN1 mechanism is not responsible for the reactions studied. We believe that it is the initiation step (eq 1 in Scheme 2) that does not occur under the experimental conditions. A final interesting question we may ask is whether there exists a feasible pathway for direct conversion of the kinetic products (3 þ 5) to the thermodynamic products (2 þ 4). If so, it would be difficult to explain the experimental observation that the kinetic products, i.e., the halogen-abstraction products 3, were 3023

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Figure 7. Transition-state structures calculated for the direct conversion of the kinetic products (3 þ 5) to the thermodynamic products (2 þ 4). Selected bond distances are given in Å. Hydrogen atoms associated with the model boryl anions and the two lithium-coordinated thf molecules are omitted for clarity.

obtained (Scheme 1). Our calculations indicate that there indeed exists a feasible pathway for the direct conversion. The reaction barriers calculated are given in Scheme 3. The transition-state structures TSC are shown in Figure 7. The calculated barriers lie in a fairly narrow range from 23 to 28 kcal/mol (Scheme 3), a result reflecting the balance of bond strength between the bonds forming (Li
X) and breaking (B
X) at the transition states (Figure 7). For example, when X = Cl, both of the bonds forming (Li
Cl) and breaking (B
Cl) at the transition states are strong and short (Figure 7). For a given R, the barriers slightly increase down the group of X = Cl, Br, and

I, indicating that the Li
X interactions at the transition states slightly dominate. The benzyl systems have slightly higher barriers than the methyl systems due to the fact that CH3
is expected to be more nucleophilic than PhCH2
. The barriers calculated for this conversion via TSC are significantly higher than those calculated for the first step via TSB. The results suggest that the halogen abstraction (the first step) is a very fast process, whereas the second step, which converts the halogen-abstraction products (3 þ 5) to the thermodynamically more stable products (2 þ 4), is a very slow process. The reported general experimental procedure for the 3024

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Organometallics reactions of the lithium boryl 1 with organohalides is as follows:24b to a thf solution of the lithium boryl 1 was added an organohalide at
45 °C, and the resulting suspension was stirred at room temperature for 10 min. Under these reaction conditions, we anticipate that the heat generated from the first step (halogen abstraction) is easily transferred to the surroundings. The second step has a significant barrier, and the reaction time is short, allowing the halogen-abstraction products to be observed. Therefore, we predict that a prolonged reaction time should eventually produce the expected SN2 substitution products RB(MeNCHdCHNMe).

’ CONCLUSIONS We have studied theoretically the mechanism of reactions of the lithium boryl LiB(R0 NCHdCHNR0 ) (R0 = 2,6-iPr2C6H3), 1, with organohalides (RX; R = CH3, CH2Ph and X = Cl, Br, I) that give RB(R0 NCHdCHNR0 ) and/or XB(R0 NCHdCHNR0 ). We found that in these reactions the lithium boryl acts as a strong nucleophile, attacking the halide-bonded carbon atom and/or the halogen atom to form RB(MeNCHdCHNMe) (an expected SN2 substitution product) and/or XB(MeNCHdCHNMe) (a halogen-abstraction product), respectively. Our calculations indicate that the reactions are all highly exergonic regardless of which products are formed. The reactions giving expected SN2 substitution products are more exergonic than those giving halogen-abstraction products (ca.
100 kcal/mol versus
40 kcal/mol). These results imply that the halogen-abstraction products obtained in these reactions are kinetically controlled because the reactions are irreversible. Despite the irreversibility, our calculations indicate that there exists a feasible pathway for direct conversion of the kinetic products [XB(MeNCHdCHNMe) þ LiR] to the thermodynamic products [RB(MeNCHdCHNMe) þ LiX]. On the basis of this result, we predict that a prolonged reaction time should eventually produce the expected SN2 substitution products RB(MeNCHdCHNMe). For the reactions of 1 with CH3X, the expected SN2 substitution pathway is kinetically favored when X = Cl, while the halogen-abstraction product is kinetically favored when X = Br and I. For the reactions of 1 with PhCH2X, the halogenabstraction pathways are kinetically favored for all X (X = Cl, Br, or I). Clearly, an organohalide having a halogen with lower electronegativity and greater ability to engage in hypervalent bonding promotes the halogen-abstraction reaction. Benzyl halides were also found to promote halogen abstraction due to conjugation, which stabilizes the benzyl anion in the transition state. Softer nucleophiles (X-philes) usually attack the halide in RX compounds.42,43 Consistent with this finding, in the current case, it is the boryl anion, a softer nucleophile than a carbanion due to the more electropositive boron, that shows preference to attack at X rather than R in an RX compound. We also examined the halogen-abstraction reaction RX þ LiR0 f R0 X þ LiR, in which a carbon nucleophile, instead of a boron nucleophile, was considered. Our calculations show that the halogen-abstraction reaction is unfavorable both kinetically (for X = Cl, Br) and thermodynamically (for X = Cl, Br, I) when compared with the normal SN2 reaction, RX þ LiR0 f R0
R þ LiX. There is no net thermodynamic driving force for a halogen abstraction to occur in any case. In contrast, the normal SN2 reaction leads to formation of a new, strong carbon
carbon bond and LiX, providing the necessary thermodynamic driving force.

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We also found that a radical nucleophilic substitution mechanism (SRN1) for the reactions of 1 with benzyl halides cannot explain the experimentally observed chemoselectivity. Therefore, we conclude that benzyl radicals are not present under the experimental conditions reported.

’ ASSOCIATED CONTENT

bS

Supporting Information. Complete ref 31 and tables giving Cartesian coordinates and electronic energies for all of the calculated structures. This material is available free of charge via the Internet at http://pubs.acs.org.

’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected]; [email protected].

’ ACKNOWLEDGMENT The authors acknowledge the financial support from the Hong Kong Research Grants Council (HKUST 602108P, HKU1/ CRF/08, and SBI09/10.SC04). T.B.M. thanks the Royal Society (U.K.) for support via an International Outgoing Short Visit Grant, the Royal Society of Chemistry for a Journals Grant for International Authors, and the EPSRC for support via an Overseas Research Travel Grant. ’ REFERENCES (1) For reviews see: (a) Hartwig, J. F.; Waltz, K. M.; Muhoro, C. N.; He, X.; Eisenstein, O.; Bosque, R.; Maseras, F. In Advances of Boron Chemistry; Siebert, W., Ed.; Spec. Publ. No. 201, The Royal Society of Chemistry: Cambridge, 1997; p 373. (b) Wadepohl, H. Angew. Chem., Int. Ed. Engl. 1997, 36, 2441. (c) Irvine, G. J.; Lesley, M. J. G.; Marder, T. B.; Norman, N. C.; Rice, C. R.; Robins, E. G.; Roper, W. R.; Whittell, G. R.; Wright, L. J. Chem. Rev. 1998, 98, 2685. (d) Braunschweig, H. Angew. Chem., Int. Ed. 1998, 37, 1786. (e) Smith, M. R., III. Prog. Inorg. Chem. 1999, 48, 505. (f) Braunschweig, H.; Colling, M. Coord. Chem. Rev. 2001, 223, 1. (g) Aldridge, S.; Coombs, D. L. Coord. Chem. Rev. 2004, 248, 535. (h) Braunschweig, H.; Kollann, C.; Rais, D. Angew. Chem., Int. Ed. 2006, 45, 5254. (i) Kays, D. L.; Aldridge, S. Struct. Bonding (Berlin) 2008, 130, 29. (j) Braunschweig, H.; Dewhurst, R. D.; Schneider, A. Chem. Rev. 2010, 110, 3924. (2) (a) Burgess, K.; Ohlmeyer, M. J. Chem. Rev. 1991, 91, 1179.(b) Burgess, K.; van der Donk, W. A. In Encyclopedia of Inorganic Chemistry; King, R. B., Ed.; Wiley: Chichester, 1994; Vol. 3, p 1420. (c) Fu, G. C.; Evans, D. A.; Muci, A. R. In Advances in Catalytic Processes; Doyle, M. P., Ed.; JAI: Greenwich, CT, 1995; p 95. (d) Beletskaya, I.; Pelter, A. Tetrahedron 1997, 53, 4957. (e) Crudden, C. M.; Edwards, D. Eur. J. Org. Chem. 2003, 4695. (3) See, for example: (a) M€anning, D.; N€ oth, H. Angew. Chem., Int. Ed. 1985, 24, 878. (b) Evans, D. A.; Fu, G. C.; Hoveyda, A. H. J. Am. Chem. Soc. 1988, 110, 6917. (c) Burgess, K.; van der Donk, W. A.; Westcott, S. A.; Marder, T. B.; Baker, R. T.; Calabrese, J. C. J. Am. Chem. Soc. 1992, 114, 9350. (d) Westcott, S. A.; Blom, H. P.; Marder, T. B.; Baker, R. T. J. Am. Chem. Soc. 1992, 114, 8863. (e) Doucet, H.; Fernandez, E.; Layzell, T. P.; Brown, J. M. Chem.—Eur. J. 1999, 5, 1320. (f) Segarra, A. M.; Guerrero, R.; Claver, C.; Fernandez, E. Chem. Commun. 2001, 1808. (g) Dembitsky, V. M.; Abu Ali, H.; Srebnik, M. Appl. Organomet. Chem. 2003, 17, 327. (h) Segarra, A. M.; Claver, C.; Fernandez, E. Chem. Commun. 2004, 464. (i) Lillo, V.; Mata, J. A.; Segarra, A. M.; Peris, E.; Fernandez, E. Chem. Commun. 2007, 2184. (j) Endo, K.; Hirokami, M.; Shibata, T. Organometallics 2008, 27, 5390. (k) Kanas, D. A.; Geier, S. J.; Vogels, C. M.; Decken, A.; Westcott, S. A. Inorg. Chem. 2008, 47, 8727. (l) Endo, K.; Hirokami, M.; Takeuchi, K.; 3025

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