Alkali Metal Adducts of an Iron(0) Complex and Their Synergistic FLP-Type Activation of Aliphatic C-X Bonds

FLP-Type Activation of Aliphatic C −X Bonds

Article

Alkali Metal Adducts of an Iron(0) Complex and Their Synergistic

‡

Hendrik Tinnermann, Simon Sung, D á niel Cs ó k á s, Zhi Hao Toh, Craig Fraser, and Rowan D. Young*

Cite This: J. Am. Chem. Soc. 2021, 143, 10700 −10708

Read Online

ACCESS

Metrics & More

Article Recommendations

sı Supporting Information

ABSTRACT: We report the formation and full characterization of

weak adducts between Li and Na cations and a neutral iron(0)

complex, [Fe(CO) (PMe ) ] (1), supported by weakly coordinat-

3 2

ing [BAr^F₂₀] anions, [1·M][BAr ₂₀] (M = Li, Na). The adducts are

found to synergistically activate aliphatic C−X bonds (X = F, Cl,

Br, I, OMs, OTf), leading to the formation of iron(II) organyl

compounds of the type [FeR(CO) (PMe ) ][BAr ₂₀], of which

3 2

several were isolated and fully characterized. Stoichiometric

reactions with the resulting iron(II) organyl compounds show

that this system can be utilized for homocoupling and cross-

coupling reactions and the formation of new C−E bonds (E = C,

H, O, N, S). Further, we utilize [1·M][BAr ] as a catalyst in a

simple hydrodehalogenation reaction under mild conditions to

showcase its potential use in catalytic reactions. Finally, the mechanism of activation is probed using DFT and kinetic experiments

that reveal that the alkali metal and iron(0) center cooperate to cleave C−X via a mechanism closely related to intramolecular FLP

activation.

INTRODUCTION

counterions are able to deprotonate arene hydrogen position-

■

4a,b

Jouikov and Mongin used a putative lithium ferrate to

The transfer of organyl groups from halides to metals is a key

concept in organic synthesis and carbon−element bond

formation. The transfer formally reduces the organyl group,

transforming its nature from electrophilic to nucleophilic, and

thus enabling the organyl moiety to be used in coupling

chemistry. In most instances, the use of highly reducing metals,

such as elemental lithium, magnesium, or zinc, or the use of

noble metals, such as rhodium or palladium, is required for

deprotonate arenes in situ for subsequent electrophilic

functionalization, and Knochel was able to metalate arene

C−H positions through the combination of an iron(II)

diamide, lithium chloride, and magnesium chloride used in

situ. To date, the ferrate components employed in both C−H

and C−X activations are both highly basic and highly reducing,

so must be handled under inert conditions. Activation of C−X

such transformations to take place. This requirement renders

or C−H bonds by non-ferrate iron systems is extremely rare.

reactions either highly expensive (when using noble metals) or

highly dangerous (when using highly reductive metals). To

circumvent these limitations, there has been a recent push to

utilize base metals for the activation and functionalization of

organic halides.

In this respect, electron-rich ferrates have been successful for

Herein, we report on the use of robust and stable

components in the synergistic activation of strong aliphatic

C−X bonds by well-characterized cationic iron(0)-alkali metal

adducts (Figure 1, C). We demonstrate their potential use in

synthesis through stoichiometric homocoupling reactions,

stoichiometric cross-coupling reactions, and catalytic hydro-

dehalogenation reactions. Finally, we explore the mechanism of

C−X activation through a combination of kinetic and DFT

studies to elucidate the origin of the unexpected synergistic

reactivity.

the activation of strong aliphatic−halide bonds allowing both

reductive homocoupling and cross-coupling reactions (Figure

, A). Such ferrates are typically supported by s-block cations,

most commonly magnesium fragments, arising from precatalyst

activation with Grignard reagents, or alkali metal counterions.

In most of these systems counter-cations are thought to play

little role in C−X bond activation and are often mechanistically

ignored unless they are in the coordination sphere of iron.

In contrast, distinct synergistic eﬀects for C−H activation/

deprotonation have been observed for multiple ferrate/s-block

Received: May 10, 2021

Published: July 12, 2021

metal combinations (Figure 1, B). For example, Mulvey and

Hevia have shown that combinations of ferrates with sodium

2021 American Chemical Society

Journal of the American Chemical Society

J. Am. Chem. Soc. 2021, 143, 10700−10708

0700

Article

In the structure of [1·Na][BAr^F₂₀] three separate molecules

of 1 bind sodium cations through their carbonyl oxygen atom

with a further ﬁve coordination sites on the sodium cation

being occupied by ﬂuorine atoms of [BAr^F] counteranions

−

(

Figure 2, D and E). Thus, a 2D-coordination polymer

network is established via sodium−carbonyl coordination

(

Figure 2, F).

The change in structure is likely resultant from a lower

coordination number restriction arising from the smaller ionic

radius of lithium (90 pm) as compared to sodium (116 pm).

Structural diﬀerences between the lithium and sodium

adducts in the solid state are supported by infrared

spectroscopy. A Nujol mull FTIR spectrum of [1·Li][BAr ₂₀]

−

displays two carbonyl bands at 1834 and 1819 cm (cf.

−

compound 1 ν_C_O= 1879 cm ), while that of [1·Na][BAr ₂₀]

−

shows two bands at 1871 and 1849 cm , indicating a weaker

Fe−CO···M interaction. This is reﬂected in the molecular

structures of [1·M][BAr^F], where the comparative Fe−CO···

Na distances {ranging from 2.331(5) to 2.732(5) Å} and Fe−

CO···Li distances {ranging from 1.952(6) to 2.031(5) Å} are

well beyond the diﬀerence in ionic radii between lithium and

Figure 1. (A) Iron ferrates are known to activate sp and sp C−X

bonds (X = Cl, Br, I). (B) Iron amides and s-block metals are

reported to synergistically deprotonate sp C−H bonds. (C) This

sodium (26 pm).

work describes synergistic activation of sp C−X bonds (X = F, Cl, Br,

I, OMs, OTf) using an iron(0) complex with lithium and sodium

salts.

Solution studies of [1·M][BAr^F₂₀] (M = Li, Na) indicate

that a degree of association is maintained between the alkali

metals and 1 (Table 1). ESI-mass spectrometry of solutions of

[

1·M][BAr^F] reveals signals at 591.0312 m/z and 607.0123

RESULTS AND DISCUSSION

■

[

m/z, corresponding to the adducts [1 ·M] (M = Li, Na),

Synthesis and Characterization of Adducts. Mixing of

respectively. P NMR spectroscopy of [1·M][BAr 20^]⁽^M⁼

Fe(CO) (PMe ) ] (1) with nonsolvated lithium or sodium

3 2

^Lⁱ^,^N^a⁾^s^h^o^w^s^a^v^e^r^y^s^lⁱ^g^h^t^u^p^ﬁ^e^l^d^s^hⁱ^f^t⁽^<¹^p^p^m⁾^o^f^t^h^e^P^M^e3

salts of the weakly coordinating borate anion [BAr ] {BAr^F

signals from 1 (δ 38.4), as well as broadening of the signals,

B(C F ) } results in the formation of adducts of the

6 5 4

indicating that dynamic alkali metal exchange likely occurs.

Indeed, an equilibrium between coordinated and “free” alkali

metal ions was established by the addition of 0.5, 1.0, and 2.0

empirical form [1·M][BAr ₂₀] (M = Li, Na) (Scheme 1).

Scheme 1. Formation of Adducts [1·M][BAr ₂₀] (M = Li,

Na)

_e_q_u_i_v_o_f_N_a_[_B_A_rF₂₀] to 1, resulting in a shift of the

resonance from δ 38.3 to 38.0 to 37.8.

H DOSY NMR experiments also establish that 1 and

M[BAr^F] (M = Li, Na) are strongly associated in solution.

For example, the H NMR signal of PMe in a sample of 1 in

,2-diﬂuorobenzene (1,2-DFB) corresponds to a diﬀusion

−

2 −1

coeﬃcient of 11.20 × 10 m s , while addition of 1 equiv of

M[BAr^F] to the sample reduces the signal’s diﬀusion

−

−1

−10

coeﬃcient to 7.37 × 10

m s (Li) or 8.93 × 10

(Na), signifying a notable increase in the apparent

hydrodynamic radii (R ) of 1 (see SI , Table S1). Addition of

K[BAr^F20] provides only a minor reduction in diﬀusion

Crystals of [1·M][BAr^F] (M = Li, Na), grown from

−1

layering ﬂuorobenzene solutions of [1·M][BAr ₂₀] with n-

hexane, reveal the solid-state structures of the adducts (Figure

−

−1

, A−F). Compound 1 has been utilized as a Lewis base

coeﬃcient to 10.93 × 10

m s , consistent with our

inability to isolate and characterize [1·K][BAr^F20] in the solid

state, although mass spectrometric data also indicated a

concentration of [1·K][BAr^F20] in solution (Table 1). Given

the relative size of the alkali metals, the DOSY NMR data

suggest that adduct formation is favored with the preference Li

> Na > K resulting in the observed average diﬀusion

coeﬃcients.

previously in frustrated Lewis pair (FLP) chemistry and in

metal-only Lewis pairs (MOLP) with both transition metals

and main group metals, allowing the direct formation of Lewis

acid−iron bonds. In contrast, 1 binds hard Lewis acidic alkali

metals through its carbonyl oxygen atoms (i.e., hard Lewis

bases). Alkali metal adducts with iron carbonyl ligands are

known, but only in ferrate complexes where a strong

electrostatic charge stabilizes the interaction.

Lithium and sodium salts of the related borate anion

[BAr^F] {BAr = tetrakis(3,5-bis(triﬂuoromethyl)phenyl)-

−

The molecular structure of the lithium adduct [1·Li]-

[

BAr^F] reveals that two carbonyls from two separate

borate} were found to form similar adducts with correlating

molecules of 1 bind each lithium atom through oxygen (κ -

O), with the remaining three coordination sites occupied by

ﬂuorine atoms of the anions (Figure 2, A and B). Thus, a

dimeric structure is established with respect to lithium/

carbonyl coordination. Concurrently, a coordination polymer

structure is formed between the lithium cations and the

spectroscopic and spectrometric data. DOSY H NMR spectra

of Na[BAr^F] added to 1 also show a decrease in the diﬀusion

−

−1

coeﬃcient to 8.04 × 10

m s . Further, the diﬀusion

coeﬃcients of the [BAr^F] anion aryl protons are reduced

−

from a sample of pure Na[BAr ₂₄] in 1,2-DFB (see Table 1),

suggesting that the anion is also interacting with 1. Indeed₋,

calculations indicated complete dissociation of the [BAr^F₂₀]

[

BAr^F] anions (Figure 2, C).

−

0701

Journal of the American Chemical Society

J. Am. Chem. Soc. 2021, 143, 10700−10708

Article

Figure 2. (A) Molecular structure of [1·Li][BAr^F₂₀], asymmetric unit. Selected bond distances (Å): Li1−O1, 1.952(6); Fe1−C1, 1.739(3). (B)

Closest contacts for 1 and Li in the structure of [1·Li][BAr ]. (C) Packing for [1·Li][BAr ] viewed along the b-axis. (D) Molecular structure of

[

1·Na][BAr ₂₀], asymmetric unit. Selected distances (Å): Na1−O1, 2.331(5); Fe1−C1, 1.752(5). (E) Closest contacts for 1 and Na in the

structure of [1·Na][BAr ]. (F) Packing for [1·Na][BAr ] viewed along the c-axis. Hydrogen atoms are omitted from all structures.

Table 1. Possible Speciation of [1·M][BAr ₂₀] in Solution

C−X Activation Chemistry. Compound 1 and the salts

M[BAr^F] (M = Li, Na, K) are separately stable in

halogenated alkane solvents and in the presence of alkyl

halides. However, the adducts [1·M][BAr^F₂₀] were found to

activate a variety of aliphatic C−X bonds under surprisingly

mild reaction conditions. For example, benzyl chloride was

completely consumed by [1·Li][BAr^F] at room temperature

in less than 5 h to generate [1-Bn][BAr ₂₀] (Table 2, entry 1).

Similarly, [1·M][BAr^F] (M = Na, K) were found to activate

benzyl chloride, albeit more slowly than [1·Li][BAr ₂₀]

Table 2. Qualitative Activation of C−X Substrates

diﬀusion rate (10 m²species observed by ESI-TOF-

‑

species

s )

11.20 (1)

7.37 (1)

+ Li[BAr^F₂₀]

[1·Li] , [1 ·Li]

+ Na[BAr^F₂₀] 8.93 (1)

[1·Na] , [1 ·Na]

₊_K_[_B_A_rF₀]

entry

substrate

salt

time/temp

conversion

10.93 (1)

[1·K]

+ Na[BAr ₂₄] 8.04 (1), 5.74 (BAr^F₂₄)

[1·Na] , [1 ·Na]

Li[BAr^F20

Na[BAr^F20

]

Na[BAr^F₂₀]

K[BAr^F₂₀]

BnCl

BnBr

BnF

BnOMs

MeOTf

t-BuCl

n-OctF

neo-PentCl

]

5 h/25 °C

72 h/25 °C

4 h/80 °C

24 h/25 °C

16 h/80 °C

5 h/25 °C

20 h/25 °C

1 h/25 °C

24 h/25 °C

16 h/25 °C

3 h/60 °C

16 h/25 °C

24 h/80 °C

100%

65%

100%

<5%

100%

60%

100%

24%

100%

<5%

6.47 (BAr^F₂₄)

Na[BAr ₂₄]

none

_L_i_[_B_A_rF₂₀]

anion from [1·Na] to be endergonic by 8.2 kcal mol⁻¹and

that the alkali metal is likely supported by the anion in

solution.

We also attempted to establish the relative thermodynamic

stability of possible adducts in solution using density functional

_L_i_[_B_A_rF₂₀]

_N_a_[_B_A_rF₂₀]

_L_i_[_B_A_rF₂₀]

theory (DFT). However, these calculations showed that many

permutations of [1 ·Na ][BAr ] (and their solvates) are

Li[BAr^F₂₀]

_L_i_[_B_A_rF₂₀]

20 y

−

possible within computational error (i.e., ±2 kcal mol ).

Although these spectroscopic, spectrometric, and computa-

tional data cannot explicitly establish the precise speciation of

CH Cl₂

CH Br₂

PhCl

[

1·M][BAr^F₂₀] in solution, they do imply that signiﬁcant

interaction between 1 and the alkali metal is persistent and that

Selected reactions from Table S2; see SI. Run in neat CH Cl . Run

the interaction follows the order Li > Na > K.

in neat PhCl.

0702

J. Am. Chem. Soc. 2021, 143, 10700−10708

Journal of the American Chemical Society

Bn, Me, MEM} are unremarkable and similar to those of [1 -

Article

(

entries 2−4, Table 2 and Figure S10, see SI ). However, in the

chloride, with only minor activation products observed (see SI,

Tables S2 and S3).

Donating solvents were also found to obstruct activation.

absence of any alkali salt, compound 1 was found to be

completely unreactive with benzyl chloride, even with

prolonged heating (entry 5, Table 2).

For instance the use of neat Et O, THF, 1,2-DME, or MeOH

Qualitative reactions between [1·M][BAr ₂₀] (M = Li, Na,

as solvents hinders the activation of benzyl chloride by [1·

M][BAr^F₂₀] (M = Li, Na) (see SI , Tables S2 and S3). This

eﬀect was illustrated by the addition of 10 equiv of pyridine to

the activation reaction of BnBr by [1·Na][BAr^F₂₀], which

K) and a number of organyl halides and pseudohalides were

undertaken to assess their reactivity patterns (Table 2 and

Table S2, see SI ). In summary, the adducts [1·M][BAr^F₂₀]

eﬃciently activated primary, secondary, and tertiary aliphatic

halides and allylic and benzylic halides. Alkyl ﬂuorides,

chlorides, bromides, iodides, mesylates, and triﬂates were

quenched the reaction, while the addition of 10 equiv of Et O

only slightly reduced the reaction rate (see SI , Figure S11). In

general, polar arene solvents (PhCl, PhF, 1,2-C H F )

4 2

activated by [1·M][BAr ₂₀] (M = Li, Na), but aryl halides

provided the best solubility and least interference with the

synergistic activation process.

possessing an sp C−X bond did not react, even at elevated

temperatures.

Compounds [1-R][BAr^F] (R = Bn, CH Cl, Me, MEM

[

1·M][BAr^F₂₀] (M = Li, Na) was found to react with

{MEM = CH O(CH ) OMe}) were isolated and fully

2 2 2

dichloromethane (DCM) at room temperature to generate [1-

CH Cl][BAr ₂₀] over a matter of days. At elevated temper-

characterized to conﬁrm the identity of a number of activation

products (Scheme 3). For example, compound [1-CH Cl]-

atures, full conversion could be achieved in 3 h (Table 2, entry

Scheme 3. Synthesis of Isolated Compounds [1-R][BAr^F₂₀]

3). This is noteworthy, as although the activation of DCM by

noble metals is well established, C−Cl cleavage of DCM by

iron (or other ﬁrst-row transition metals) is extremely rare and

(R = CH Cl, Me, MEM, Bn) from Reaction between [1·

M][BAr^F₂₀] (M = Li, Na) with DCM, MEMCl, MeOTf, and

BnOMs, Respectively

exempliﬁes the enhanced synergetic reactivity of [1·M]-

BAr^F₂₀].

[

In substrates with α-hydrogen atoms relative to the C−X

bond, β-hydride elimination of the iron alkyl activation product

resulted in generation of [1-H][BAr ₂₀] and concomitant

formation of alkene byproduct (Scheme 2). Further, in the

Scheme 2. Reactivity of [1·M][BAr ₂₀] (M = Li, Na) with

_B_A_rF ] could be isolated in 44% yield and is identiﬁed by a

[

Alkyl, Benzyl, and Allyl Halides

triplet signal at 3.36 ppm ( J = 8.3 Hz) in the H NMR

spectrum arising from the chloromethyl ligand and a single P

NMR resonance at δ 12.9. The chloromethyl ligand could also

be identiﬁed in the C NMR spectrum of [1-CH Cl][BAr ₂₀]

as a triplet signal at 32.4 ppm (t, J = 14.1 Hz). FTIR

spectroscopy reveals three carbonyl stretching bands at 1990,

−

043, and 2095 cm , indicative of an iron(II) center. The

molecular structure of [1-CH Cl][BAr ₂₀] displays octahedral

geometry and conﬁrms the activation of DCM, with a

chloromethyl ligand observed to occupy an equatorial position

with the three carbonyl ligands, while the phosphine ligands

remain in the axial positions (Figure 3).

The characterization data of compounds [1-R][BAr^F₂₀] {R =

In the case of alkyl halides with an α-hydrogen, β-hydride

elimination led to [1-H] . In the case of benzyl and allyl chlorides

and bromides, homocoupling led to [1-X] (X = Cl, Br). Iron organyl,

hydride, and halide complexes could be reduced to the starting

material (1) with borohydride reductant. Anions are omitted for

clarity.

presence of excess benzylic halides homocoupling was

observed to generate the corresponding bibenzyl products

and iron halide byproducts [1-X][BAr ₂₀] (X = Cl, Br).

These complexes were also synthesized independently to verify

their observed data.

Figure 3. Molecular structures of [1-CH Cl][BAr 20^]^,^[¹^-^M^E^M^]^-

As stated above, lithium and sodium salts of the related

−

[BAr ₂₀], and [1-Me][BAr ₂₀]. Hydrogen atoms and anion omitted;

thermal ellipsoids shown at 50%. Selected bond distances (Å) and

borate anion [BAr ₂₄] provided similar adduct formation and

activation chemistry to M[BAr ₂₀] (M = Li, Na) salts.

angles (deg): for [1-CH Cl] , Fe1−P1, 2.278(1); Fe1−P2, 2.270(1);

However, no evidence was observed for adducts between 1

Fe1−C1, 2.081(3); C1−Fe1−C4, 178.5(1); P1−Fe1−P2, 175.6(1);

and group 1 metal salts containing less weakly coordinating

for [1-MEM] , Fe1−P1, 2.266(1); Fe1−P2, 2.284(1); Fe1−C1,

−

counteranions ([BF ] , [PF ] , [SbF ] , [BPh ] , [OTf] ,

2.078(4); C1−Fe1−C6, 176.3(2); P1−Fe1−P2 173.6(1); for [1-

−

[

ClO ] ). Nonetheless, combinations of 1 with a variety of

Me] , Fe1−P1, 2.263(1); Fe1−P2, 2.264(1); Fe1−C1, 2.06(2); P1−

alkali metal salts were tested for the activation of benzyl

Fe1−P2 177.3(1).

0703

J. Am. Chem. Soc. 2021, 143, 10700−10708

Journal of the American Chemical Society

solvent (0.5 mL). Yields determined by H NMR spectroscopy.

Article

CH Cl][BAr^F₂₀], but conﬁrm the installation of MEM, Me,

and Bn alkyl groups onto the iron center in their respective

compounds.

Functionalization Chemistry and Potential Use in

Catalysis. To demonstrate the synthetic potential of this

system, some simple stoichiometric and catalytic organic

transformations were explored. Complexes [1-R][BAr ₂₀], [1-

H][BAr^F₂₀], and [1-X][BAr ₂₀] could be reduced with soluble

forms of borohydride {viz., [NEt ][BH ] or Li[BH ]} to

cleanly re-form 1 with concomitant formation of the

−

corresponding [BAr ₂₀] salts (Scheme 2). In the cases of

[

1-R][BAr^F₂₀], the alkyl ligand was liberated as the

corresponding alkane in near-quantitative yield (Scheme 4,

Scheme 4. (A) Reaction of [1-R] with M[BH ] (M = Li,

NEt ); (B) Reactions between [1-R] and Nucleophiles; (C)

Reaction between [1-R] and Benzyl Chloride

Figure 4. Homocoupling of benzyl halides using stoichiometric

quantities of in situ generated [1·Na][BAr ₂₄]. General conditions: 1

(

0.04 mmol), Na[BAr ] (0.04 mmol), substrate (0.08 mmol),

Anions omitted for clarity. See SI for details.

A). Compounds [1-R][BAr^F₂₀] (R = Bn, Me, MEM) were also

probed with various nucleophiles to generate cross-coupled

products (Scheme 4, B). Concurrent with the reaction with

these nucleophiles, compound 1 was generated as the major

byproduct. Compounds [1-R][BAr ₂₀] (R = MEM, Bn) also

facilitated formal reductive coupling with electrophiles; for

example reaction of [1-MEM][BAr ₂₀] with BnCl generated

Figure 5. Catalytic reduction of aliphatic halides using 10 mol % of

the cross-coupled product MEM-Bn in 22% yield along with

1·Na][BAr ]. General conditions: 1 (0.01 mmol), Na[BAr^F20^]

[

₁_-_C_l_]_[_B_A_rF ] (Scheme 4, C), while [1-Bn][BAr ] generated

[

(

0.01 mmol), substrate (0.1 mmol), PhCl (0.5 mL), Et O (0.05 mL),

bibenzyl in 81% yield under the same conditions.

The high yield of bibenzyl from reaction of [1-Bn][BAr ]

Li[BH] (0.5 mmol). Yields determined by H NMR spectroscopy.

Reaction performed at 60 °C. Both bromides reduced. CF CH-

with BnCl led us to explore stoichiometric reductive

(

OH)CF used in place of Et O.

homocouplings using [1·Na][BAr ₂₄] with organyl halides

c,14

(Figure 4).

Under relatively mild conditions, most benzyl

halide substrates gave good to excellent yields of their

corresponding bibenzyl products (Figure 4, entries 1−7).

Allylic bromides also produced homocoupled products in low

yields (Figure 4, entry 8); however, for substrates containing α-

hydrogen atoms (relative to the halide position), fast β-hydride

elimination generated the iron hydride [1-H][BAr^F₂₄] and

prevented the homocoupling reaction.

tively under the same conditions (Figure 5). In these reactions,

a small amount of Et O was added to assist dissolution of

Li[BH ]; however, it was found that higher concentrations of

Et O disrupted synergistic cooperation between 1 and Na and

hindered C−X activation.

A brief substrate scope assay showed that a range of alkyl

halides (benzylic and nonbenzylic) could be catalytically

reduced in moderate to good yields, with aliphatic chlorides

proving more diﬃcult than aliphatic bromides, as would be

expected (Figure 5). More importantly, this reaction

exempliﬁes the synthetic potential of this mild synergistic

system, and we are currently developing other catalytic

reactions using [1·M][BAr^F₂₀] (M = Li, Na) focused on C−

C and C−E (E = N, O, S) coupling reactions.

Finally, given that the elements of C−X activation and

reduction of activation compounds [1-R][BAr ] to re-form 1

have been demonstrated above, we developed a simple

catalytic reaction allowing for hydrodehalogenation of alkyl

halides (Figure 5). In the absence of [1·M][BAr ₂₀] (M = Li,

Na), Li[BH ] acts as a poor reductant for aliphatic halides, as

evidenced by the direct reaction of benzyl bromide and

Li[BH ] giving less than 10% yield of toluene after 22 h at

Mechanistic Insight into C−X Activation. We postu-

lated that coordination of the alkali metal (Li or Na) to the

room temperature. In contrast, the addition of catalytic

amounts of [1·Na][BAr ₂₀] reduces benzyl bromide quantita-

alkyl halide position likely reduces the barrier for S 2 attack by

0704

J. Am. Chem. Soc. 2021, 143, 10700−10708

Journal of the American Chemical Society

, in a mechanism reminiscent of FLP activation of alkyl, silyl,

Article

and germyl ﬂuorides. A series of kinetic experiments were

performed to support our hypothesis. Initial rate experiments

between BnBr, 1, and Na[BAr ₂] reveal that the reaction is

ﬁrst order with respect to 1, BnBr, and Na[BAr ₂₀] (Figures

S3−S8, see SI). These data suggest an S 2-type activation

involving [1·Na][BAr ] rather than larger dimetallic species

such as [1 ·Na][BAr ₂₀], which would be expected to follow a

second-order rate in 1, assuming a fast equilibrium between

dimeric and monomeric species.

Evidence for a Lewis acid assisted S 2 mechanism was also

obtained from a Hammett plot from the activation of various

benzyl bromides (Figure S13 ). The Hammett plot provided a

ρ-value of −2.7, indicative of modest electron ﬂow away from

the benzyl aromatic ring in the transition state. This is

consistent with coordination of a Lewis acid to the benzyl

bromide position in the transition state. In contrast, S 1-type

activations have ρ-values below −4, and radical benzyl addition

to iron is reported to have a positive ρ-value.

To further rule out the possibility of a radical pathway for

the activation of benzyl halides, 10 equiv of the radical

scavenger 1,4-methylcyclohexadiene (1,4-CHD) was added to

a reaction between BnBr and [1·Na][BAr ₂₀]. The presence of

,4-CHD made no diﬀerence to the rate of reaction or yield of

[

1-Bn] (see SI , Table S2). However, 1,4-methylcyclohex-

adiene was found to signiﬁcantly reduce the yield of the

reductive homocoupling reaction for BnBr (Table S3, see SI),

implying that reaction of BnBr with [1-Bn] does proceed via a

radical mechanism.

The activation of C−X bonds by [1·M][BAr ₂₀] was also

interrogated computationally using DFT. As a model system,

we focused on the activation of benzyl bromide to generate [1-

Bn] . Although a number of mechanistic possibilities were

considered (see SI , DFT studies, alternative pathways), we

focused our attention on the reaction pathway involving S_N2

attack of BnBr by 1 in the presence and absence of alkali metal

cations. The reaction proﬁle was calculated with a number of

functionals (viz., ωB97X-D, M06, M06L), and anion and

solvation eﬀects were also modeled (see SI , Figures S82−S88).

However, similar trends and activation barriers were

consistently observed regardless of the functional employed.

Figure 6 exempliﬁes the observed reaction trend in the

presence and absence of M (M = Li, Na, K). In the absence of

Figure 6. Calculated reaction proﬁle for the nucleophilic activation of

any alkali metal cation, the barrier to C−Br activation is

BnBr by 1 with and without M (M = Li, Na, K) assistance (wB97X-

−

−1

kinetically inaccessible (>30 kcal mol ). However, the

inclusion of Li, Na, or K lowers the transition state barrier

by 15.0 to 11.3 kcal mol⁻(relative to the ground state) with

the activation barriers following the order Li < Na < K. This

result was corroborated with experimental kinetic data that

D/Def2TZVPP//wB97X-D/Def2SVP(SMD), kcal mol ). Calcu-

lated structures for TS-1 included as insets with bond distances

given in Å.

employing Collman’s reagent that are hindered by coordinated

showed the activation of BnBr by [1·M][BAr ₂₀] (M = Li, Na,

K) followed the reaction rate order of Li ≫ Na > K (see SI,

alkali metals.

The computed free energy data lend strong support to our

Figure S10).

mechanistic proposal that the reaction proceeds via an

The inclusion of the alkali metal transforms the reaction

from endergonic to exergonic, providing thermodynamic drive

“assisted” S

2 mechanism wherein the M alkali metal cation

contributes to a pronounced reduction in activation barrier

height, mimicking FLP-type reactivity. Such a mechanism is a

distinct departure from oxidative addition, nucleophilic, and

radical processes more commonly observed in ﬁrst-row

for the formation of [1-Bn] . In addition, precipitation of metal

halide salt from activation reactions aided formation of [1-

Bn] , which is not captured with these computational results.

Notably, calculations predict that C−X activation by [1·M]

,20

transition metal alkyl halide activation.

proceeds via an intramolecular FLP-type transition state (TS-1,

with the alkali metal supported by the carbonyl ligand during

the activation step. This transition state is reminiscent of

calculated structures involved in the intramolecular FLP-type

SUMMARY

■

In summary, we have found that in the absence of any

competing base, lithium and sodium cations form weak

adducts with 1 {[1·M][BAr^F₂₀] (M = Li, Na)}, bonding

activation of H by (LiP Bu ) and is distinct from reactions

2 n

0705

J. Am. Chem. Soc. 2021, 143, 10700−10708

Journal of the American Chemical Society

Chem. Rev. 2015 , 115 , 3170. (b) Chirik, P.; Morris, R. Iron- and

Article

through the carbonyl oxygen atoms. The cations in [1·

Author Contributions

H.T. and S.S. contributed equally.

Notes

M][BAr^F] (M = Li, Na) are further supported by their

‡

weakly coordinating [BAr ₂₀] counteranions in the solid state,

forming a coordination polymer, but likely exist as a dynamic

mixture of adducts in solution. The introduction of aliphatic

halides to solutions of [1·M][BAr^F₂₀] (M = Li, Na) results in

C−X activation (X = F, Cl, Br, I, OMs, OTf) and the

formation of iron(II) organyls of the type [1-R][BAr^F]. The

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

We thank the Singapore Agency for Science, Technology and

Research (A*STAR Grant No. A1983c0033) for ﬁnancial

support.

remarkable enhanced reactivity aﬀorded to 1 by the

coordinated alkali metals means that their role in other iron-

mediated C−X activation reactions should not be overlooked.

It is shown that installed organyl ligands on compounds [1-

R][BAr^F] (R = CH Cl, Me, Bn, MEM) can undergo

REFERENCES

■

(

1) Knochel, P.; Molander, G. A. Comprehensive Organic Synthesis,

2nd ed.; Elsevier: Amsterdam, The Netherlands, 2014.

subsequent functionalization through cross-coupling and

homocoupling reactions, resulting in the formation of new

C−H, C−C, C−O, C−S, and C−N bonds. The catalytic

(2) (a) Bauer, I.; Knölker, H.-J. Iron Catalysis in Organic Synthesis.

Cobalt-Catalyzed Alkene Hydrogenation: Catalysis with Both Redox-

Active and Strong Field Ligands. Acc. Chem. Res. 2015, 48, 2495.

potential of [1·M][BAr ] (M = Li, Na) is demonstrated

(

c) Bolm, C. A new iron age. Nat. Chem. 2009 , 1 , 420.

3) (a) Mako, T. L.; Byers, J. A. Recent advances in iron-catalysed

cross coupling reactions and their mechanistic underpinning. Inorg.

Chem. Front. 2016 , 3 , 766. (b) Sherry, B. D.; Furstner, A. The

through hydrodehalogenation reactions with Li[BH ]. The

Res. 2008 , 41 , 1500. (c) Hill, D. H.; Parvez, M. A.; Sen, A.

expansion of potentially useful functionalization reactions

using this synergistic system is still under investigation.

Finally, the mechanism of our reaction was revealed through

DFT analysis and kinetic experiments. These predict an

intramolecular bimetallic cooperative FLP-type pathway, which

represents a clear departure from conventional metal-mediated

C−X activations.

Promise and Challenge of Iron-Catalyzed Cross Coupling. Acc. Chem.

Mechanistic Aspects of the Reaction of Anionic Iron(0)-Olefin

Complexes with Organic Halides. Detection and Characterization of

Paramagnetic Organometallic Intermediates. J. Am. Chem. Soc. 1994,

16 , 2889. (d) Jonas, K.; Schieferstein, L.; Kruger, C.; Tsay, Y.-H.

Tetrakis(ethylene)irondilithium and Bis(η -1,5-cyclooctadiene)-

irondilithium. Angew. Chem., Int. Ed. Engl. 1979 , 18 , 550.

ASSOCIATED CONTENT

sı Supporting Information

■

e) Bazhenova, T. A.; Kachapina, L. M.; Shilov, A. E. Mono- and

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/jacs.1c04815.

binuclear σ -aryl iron-lithium hydrides; synthesis and molecular

structure. J. Organomet. Chem. 1992, 428, 107. (f) Alonso, P. J.;

Arauzo, A. B.; Fornies, J.; Garcia-Monforte, M. A.; Martin, A.;

Martinez, J. I.; Menjon, B.; Rillo, C.; Saiz-Garitaonandia, J. J. A

square-planar organoiron(III) compound with a spin-admixed state.

Experimental details and crystallographic data (PDF)

Accession Codes

Angew. Chem., Int. Ed. 2006, 45, 6707. (g) Furstner, A.; Martin, R.;

CCDC 2046930 −2046935 and 2081859 contain the supple-

mentary crystallographic data for this paper. These data can be

obtained free of charge via www.ccdc.cam.ac.uk/data_request/

cif, or by emailing data_request@ccdc.cam.ac.uk, or by

contacting The Cambridge Crystallographic Data Centre, 12

Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

Krause, H.; Seidel, G.; Goddard, G.; Lehmann, C. W. Preparation,

Structure, and Reactivity of Nonstabilized Organoiron Compounds.

Implications for Iron-Catalyzed Cross Coupling Reactions. J. Am.

Chem. Soc. 2008 , 130 , 8773. (h) Sun, C.-L.; Krause, H.; Furstner, A. A

Practical Procedure for Iron-Catalyzed Cross-Coupling Reactions of

Sterically Hindered Aryl-Grignard Reagents with Primary Alkyl

Halides. Adv. Synth. Catal. 2014, 356, 1281. (i) Bedford, R. B.;

Brenner, P. B.; Carter, E.; Cogswell, P. M.; Haddow, M. F.; Harvey, J.

N.; Murphy, D. M.; Nunn, J.; Woddall, C. H. TMEDA in iron-

catalyzed Kumada coupling: amine adduct versus homoleptic ″ate ″

complex formation. Angew. Chem., Int. Ed. 2014, 53, 1804. (j) Al-

Afyouni, M. H.; Fillman, K. L.; Brennessel, W. W.; Neidig, M. L.

Isolation and Characterization of a Tetramethyliron(III) Ferrate: An

Intermediate in the Reduction Pathway of Ferric Salts with MeMgBr.

AUTHOR INFORMATION

■

Corresponding Author

Rowan D. Young − Department of Chemistry, National

University of Singapore, Singapore 117543, Singapore;

orcid.org/0000-0001-7437-8944; Email: rowan.young@

nus.edu.sg

J. Am. Chem. Soc. 2014, 136, 15457. (k) Munoz, S. B., III; Daifuku, S.

Authors

L.; Brennessel, W. W.; Neidig, M. L. Isolation, Characterization, and

−

Reactivity of Fe Me : Kochi ’s S = 1/2 Species in Iron-Catalyzed

Hendrik Tinnermann − Department of Chemistry, National

University of Singapore, Singapore 117543, Singapore

Simon Sung − Department of Chemistry, National University

of Singapore, Singapore 117543, Singapore; orcid.org/

Cross-Couplings with MeMgBr and Ferric Salts. J. Am. Chem. Soc.

016 , 138 , 7492. (l) Zhurkin, F. E.; Wodrich, M. D.; Hu, X. A

Monometallic Iron(I) Organoferrate. Organometallics 2017, 36, 499.

m) Munoz, S. B., III; Daifuku, S. L.; Sears, J. D.; Baker, T. M.;

(

000-0002-7864-7694

Carpenter, S. H.; Brennessel, W. W.; Neidig, M. L. The N-

Methylpyrrolidone (NMP) Effect in Iron-Catalyzed Cross-Coupling

with Simple Ferric Salts and MeMgBr. Angew. Chem., Int. Ed. 2018,

57 , 6496. (n) Parchomyk, T.; Demeshko, S.; Meyer, F.; Koszinowski,

K. Oxidation States, Stability, and Reactivity of Organoferrate

Complexes. J. Am. Chem. Soc. 2018 , 140 , 9709. (o) Weinberger, B.;

Tanguy, G.; Des Abbayes, H. A mild phase transfer synthesis of the

ylid adduct (CO) FeCH P(C H ) from iron pentacarbonyl and

Dániel Csókás − Department of Chemistry, National

University of Singapore, Singapore 117543, Singapore;

orcid.org/0000-0002-4150-477X

Zhi Hao Toh − Department of Chemistry, National University

of Singapore, Singapore 117543, Singapore

Craig Fraser − Department of Chemistry, National University

of Singapore, Singapore 117543, Singapore

5 3

dichloromethane: Evidence for the transient generation of the

tetracarbonyl ferrate anion Fe(CO)₄ . J. Organomet. Chem. 1985,

280, C31. (p) Collman, J. P.; Finke, R. G.; Cawse, J. N.; Brauman, J. I.

2 −

Complete contact information is available at:

https://pubs.acs.org/10.1021/jacs.1c04815

0706

J. Am. Chem. Soc. 2021, 143, 10700−10708

Journal of the American Chemical Society

Oxidative-addition reactions of the disodium tetracarbonylferrate

Article

supernucleophile. J. Am. Chem. Soc. 1977 , 99 , 2515. (q) Collman, J. P.

Disodium tetracarbonylferrate, a transition metal analog of a Grignard

reagent. Acc. Chem. Res. 1975, 8, 342.

iridium(I) phosphine complexes. Synthesis and structures of fac-

[Rh(PMe ) Cl (CH PMe )]Cl ·CH Cl and trans-[Rh-

(Me PCH CH PMe ) Cl(CH Cl)]Cl. J. Chem. Soc., Chem. Commun.

1987 , 0 , 1543. (b) Blank, B.; Glatz, G.; Kempe, R. Single and Double

C-Cl-Activation of Methylene Chloride by P,N-ligand Coordinated

Rhodium Complexes. Chem. - Asian J. 2009, 4 , 321. (c) Adams, G.

M.; Chadwick, F. M.; Pike, S. D.; Weller, A. S. A CH Cl complex of a

(4) (a) Albores, P.; Carella, L. M.; Clegg, W.; Garcia-Alvarez, P.;

Kennedy, A. R.; Klett, J.; Mulvey, R. E.; Rentschler, E.; Russo, L.

Direct C-H Metalation with Chromium(II) and Iron(II): Transition-

Metal Host/Benzenediide Guest Magnetic Inverse-Crown Com-

plexes. Angew. Chem., Int. Ed. 2009, 48, 3317. (b) Maddock, L. C.

H.; Nixon, T.; Kennedy, A. R.; Probert, M. R.; Clegg, W.; Hevia, E.

Utilising Sodium-Mediated Ferration for Regioselective Functionali-

sation of Fluoroarenes via C −H and C −F Bond Activations. Angew.

Chem., Int. Ed. 2018, 57, 187. (c) Nagaradja, E.; Chevallier, F.;

Roisnel, T.; Jouikov, V.; Mongin, F. Deprotonative metalation of

aromatic compounds using mixed lithium −iron combinations.

Tetrahedron 2012 , 68 , 3063. (d) Wunderlich, S. H.; Knochel, P.

Preparation of Functionalized Aryl Iron(II) Compounds and a

Nickel-Catalyzed Cross-Coupling with Alkyl Halides. Angew. Chem.,

Int. Ed. 2009, 48, 9717.

[Rh(pincer)] cation. Dalton Trans. 2015, 44, 6340. (d) Abo-Amer,

A.; McCready, M. S.; Zhang, F.; Puddephatt, R. J. The role of solvent

in organometallic chemistry  Oxidative addition with dichloro-

methane or chloroform. Can. J. Chem. 2012 , 90 , 46. (e) Huser, M.;

Youinou, M. T.; Osborn, J. A. Chlorocarbon Activation: Catalytic

Carbonylation of Dichloromethane and Chlorobenzene. Angew.

Chem., Int. Ed. Engl. 1989, 28, 1386.

(12) (a) Kandler, H.; Bidell, W.; Jänicke, M.; Knickmeier, M.;

Veghini, D.; Berke, H. Functionalized Iron Ketene Complexes from

Carbonyl Coupling Reactions. Organometallics 1998, 17, 960.

(b) Ghisolfi, A.; Condello, F.; Fliedel, C.; Rosa, V.; Braunstein, P.

Facile and Room-Temperature Activation of C _s _p ₃ −Cl Bonds by

Cheap and Air-Stable Nickel(II) Complexes of (N-Thioether) DPPA-

Type Ligands. Organometallics 2015, 34, 2255. (c) Csok, Z.;

Vechorkin, O.; Harkins, S. B.; Scopelliti, R.; Hu, X. Nickel Complexes

5) (a) Strohmeier, W.; Mu

ller, F.-J. Notiz zur photochemischen

Herstellung von Eisenpentacarbonyl-Derivaten. Chem. Ber. 1969 , 102 ,

613. (b) Bigorgne, M. Etude spectroscopique Raman et infrarouge

de Fe(CO) , Fe(CO) L et trans-Fe(CO) L (L = PMe , AsMe ,

of a Pincer NN Ligand: Multiple Carbon −Chloride Activation of

SbMe ) I. Attribution des bandes de Fe(CO) . J. Organomet. Chem.

CH Cl and CHCl Leads to Selective Carbon −Carbon Bond

1970, 24, 211.

Formation. J. Am. Chem. Soc. 2008, 130 , 8156.

6) Tinnermann, H.; Fraser, C.; Young, R. D. Zero valent iron

(13) Pank

complexes de la serie des derives halocarbonyle due fer: [FeX-

owski, M.; Bigorgne, M. Syntheses et isomerisation de

complexes as base partners in frustrated Lewis pair chemistry. Dalton

Trans. 2020, 49, 15184.

−

(CO)₅ ₋_n L ] , FeX (CO) L et [FeX (CO) ] (L = PMe ; n = 1, 2,

4 −n

7) (a) Braunschweig, H.; Dewhurst, R. D.; Hupp, F.; Schneider, C.

3; X = Cl, Br, I). J. Organomet. Chem. 1977, 125, 231.

Silver(i) and thallium(i) cations as unsupported bridges between two

metal bases. Chem. Commun. 2014, 50, 15685. (b) Braunschweig, H.;

Dewhurst, R. D.; Hupp, F.; Kaufmann, C.; Phukan, A. K.; Schneider,

C.; Ye, Q. Gauging metal Lewis basicity of zerovalent iron complexes

via metal-only Lewis pairs. Chem. Sci. 2014 , 5 , 4099. (c) Demerseman,

(14) For examples of iron-mediated Wurtz couplings, see:

(a) Khurana, J. M.; Sushma, C.; Maikap, G. C. Facile reductive

coupling of benzylic halides with ferrous oxalate dihydrate. Org.

Biomol. Chem. 2003 , 1 , 1737. (b) Nakanishi, S.; Oda, T.; Ueda, T.;

Otsuji, Y. Reaction of benzylic and allylic halides with iron-carbonyl

clusters. Chem. Lett. 1978 , 7 , 1309. (c) Buu-Hoi, N. P.; Hoan, N. The

reaction of α -halogenated arylalkanes with metal powders in

hydroxylated media. J. Org. Chem. 1949 , 14 , 1023. (d) Onuma, K.;

Yamashita, J.; Hashimoto, H. The reductive coupling reactions of

some chloromethylbenzene derivatives with iron(II) complexes. II.

Reduction by anhydrous iron(II) chloride and lithium chloroferrate-

(II). Bull. Chem. Soc. Jpn. 1973, 46, 333.

(15) For examples of catalytic hydrodehalogenation of aliphatic

halides, see: (a) Haibach, M. C.; Stoltz, B. M.; Grubbs, R. H. Catalytic

Reduction of Alkyl and Aryl Bromides Using Propan-2-ol. Angew.

Chem., Int. Ed. 2017, 56, 15123. (b) Narayanam, J. M. R.; Tucker, J.

W.; Stephenson, C. R. J. Electron-Transfer Photoredox Catalysis:

Development of a Tin-Free Reductive Dehalogenation Reaction. J.

Am. Chem. Soc. 2009 , 131 , 8756. (c) Alonso, F.; Beletskaya, I. P.; Yus,

M. Metal-Mediated Reductive Hydrodehalogenation of Organic

Halides. Chem. Rev. 2002, 102, 4009.

B.; Bouquet, G.; Bigorgne, M. Basicite

des complexes trans-

L (CO) Fe liaisons fer-mercure dans les complexes L (CO) Fe →

−

HgX ↔ [L (CO) Fe-HgX] X . J. Organomet. Chem. 1972, 35, 341.

m−

(8) For examples of alkali metal adducts of [FeL (CO)] , see:

a) Sciarone, T. J. J.; Nijhuis, C. A.; Meetsma, A.; Hessen, B.

Synthesis and reactivity of mono(amidinate) organoiron(ii) com-

plexes. Dalton Trans. 2006 , 4896. (b) Loewen, N. D.; Berben, L. A.

Secondary Coordination Sphere Design to Modify Transport of

Protons and CO . Inorg. Chem. 2019, 58, 16849. (c) Wright, R. J.;

Zhang, W.; Yang, X.; Fasulo, M.; Tilley, T. D. Isolation, observation,

and computational modeling of proposed intermediates in catalytic

proton reductions with the hydrogenase mimic Fe (CO) S C H .

Dalton Trans. 2012 , 41 , 73. (d) Saouma, C. T.; Lu, C. C.; Day, M. W.;

Peters, J. C. CO reduction by Fe(i): solvent control of C −O cleavage

versus C −C coupling. Chem. Sci. 2013, 4 , 4042. (e) Joseph, C.;

Kuppuswamy, S.; Lynch, V. M.; Rose, M. J. Fe Mo Cluster with Iron-

Carbide and Molybdenum-Carbide Bonding Motifs: Structure and

Selective Alkyne Reductions. Inorg. Chem. 2018, 57, 20. (f) Oberem,

E.; Roesel, A. F.; Rosas-Hernández, A.; Kull, T.; Fischer, S.;

Spannenberg, A.; Junge, H.; Beller, M.; Ludwig, R.; Roemelt, M.;

Francke, R. Mechanistic Insights into the Electrochemical Reduction

(16) (a) Cabrera-Trujillo, J. J.; Fernandez, I. Understanding the C −

F Bond Activation Mediated by Frustrated Lewis Pairs: Crucial Role

of Noncovalent Interactions. Chem. - Eur. J. 2021 , 27 , 3823.

(b) Mandal, D.; Gupta, R.; Young, R. D. Selective Monodefluorina-

tion and Wittig Functionalization of gem-Difluoromethyl Groups to

Generate Monofluoroalkenes. J. Am. Chem. Soc. 2018, 140 , 10682.

Lewis-Pair-Meditated Selective Single Fluoride Substitution in

Trifluoromethyl Groups. J. Am. Chem. Soc. 2020, 142 , 2572.

(d) Gupta, R.; Jaiswal, A. K.; Mandal, D.; Young, R. D. A Frustrated

Lewis Pair Solution to a Frustrating Problem: Mono-Selective

Functionalization of C −F Bonds in Di- and Trifluoromethyl Groups.

Synlett 2020 , 31 , 933. (e) Gupta, R.; Mandal, D.; Jaiswal, A. K.;

Young, R. D. FLP-Catalyzed Monoselective C −F Functionalization in

Polyfluorocarbons at Geminal or Distal Sites. Org. Lett. 2021, 23,

1915. (f) Kameo, H.; Yamamoto, H.; Ikeda, K.; Isasa, T.; Sakaki, S.;

Matsuzaka, H.; García-Rodeja, Y.; Miqueu, K.; Bourissou, D.

Fluorosilane Activation by Pd/Ni →Si −F →Lewis Acid Interaction:

An Entry to Catalytic Sila-Negishi Coupling. J. Am. Chem. Soc. 2020,

of CO Catalyzed by Iron Cyclopentadienone Complexes. Organo-

metallics 2019, 38, 1236. (g) Wang, Q.; Manzano, R. A.; Tinnermann,

H.; Sung, S.; Leforestier, B.; Krämer, T.; Young, R. D. Angew. Chem.,

Int. Ed. 2021, DOI: 10.1002/anie.202104130.

(9) Liu, Z.; Lee, J. H. Q.; Ganguly, R.; Vidovic, D. A Well-Defined

Aluminum-Based Lewis Acid as an Effective Catalyst for Diels −Alder

Transformations. Chem. - Eur. J. 2015 , 21 , 11344.

(10) Shannon, R. D. Revised effective ionic radii and systematic

studies of interatomic distances in halides and chalcogenides. Acta

Crystallogr., Sect. A: Cryst. Phys., Diffr., Theor. Gen. Crystallogr. 1976,

A32, 751.

(

11) For examples of noble metal activation of DCM, see:

a) Marder, T. B.; Fultz, W. C.; Calabrese, J. C.; Harlow, R. L.;

Milstein, D. Activation of dichloromethane by basic rhodium(I) and

(

0707

J. Am. Chem. Soc. 2021, 143, 10700−10708

Journal of the American Chemical Society

Bourissou, D. Pd/Ni-Catalyzed Germa-Suzuki coupling via dual Ge −

Article

42, 14039. (g) Kameo, H.; Mushiake, A.; Isasa, T.; Matsuzaka, H.;

F bond activation. Chem. Commun. 2021, 57, 5004.

(17) Hedström, A.; Izakian, Z.; Vreto, I.; Wallentin, C.-J.; Norrby,

P.-O. On the Radical Nature of Iron-Catalyzed Cross-Coupling

Reactions. Chem. - Eur. J. 2015, 21, 5946.

(18) For examples of 1,4-CHD being used as a radical scavenger,

see: (a) Mutra, M. R.; Kudale, V. S.; Li, J.; Tsai, W.-H.; Wang, J.-J.

Alkene versus alkyne reactivity in unactivated 1,6-enynes: regio- and

chemoselective radical cyclization with chalcogens under metal- and

oxidant-free conditions. Green Chem. 2020, 22, 2288. (b) González, I.;

Pla-Quintana, A.; Roglans, A.; Dachs, A.; Sola, M.; Parella, T.; Farjas,

J.; Roura, P.; Lloveras, V.; Vidal-Gancedo, J. Ene reactions between

two alkynes? Doors open to thermally induced cycloisomerization of

macrocyclic triynes and enediynes. Chem. Commun. 2010, 46, 2944−

19) Xu, M.; Jupp, A. R.; Qu, Z.-W.; Stephan, D. W. Alkali Metal

946.

Species in the Reversible Activation of H . Angew. Chem., Int. Ed.

20) (a) Carmona, E.; Marin, J. M.; Paneque, M.; Poveda, M. L.

018, 57, 11050.

New nickel o-methylbenzyl complexes. Crystal and molecular

structures of Ni(η -CH C H -o-Me)Cl(PMe ) and Ni (η -

CH C H -o-Me) (PMe ) (μ -OH) . Organometallics 1987 , 6 , 1757.

(b) Zell, T.; Radius, U. Carbon Halide Bond Activation of Benzyl

Chloride and Benzyl Bromide Using An NHC-Stabilized Nickel(0)

Complex. Z. Anorg. Allg. Chem. 2011 , 637 , 1858. (c) Lu, Z.; Fu, G. C.

Alkyl −Alkyl Suzuki Cross-Coupling of Unactivated Secondary Alkyl

Chlorides. Angew. Chem., Int. Ed. 2010, 49, 6676. (d) Ates i̧ n, T. A.; Li,

T.; Lachaize, S.; Brennessel, W. W.; García, J. J.; Jones, W. D.

Experimental and Theoretical Examination of C −CN and C −H Bond

Activations of Acetonitrile Using Zerovalent Nickel. J. Am. Chem. Soc.

2007, 129, 7562.

0708