ACS Catalysis
Letter
Scheme 1. Molybdenum Catalyzed N-Alkylation of Anilines
or Nitroarenes with Alcohols
realized. As part of our ongoing interest in BA/HA,12,19,23
herein, we reported the first example of a non-noble Mo catalytic
system for this transformation (Scheme 1c).
Figure 1. (a) The M−H bonding orbital energies (eV) for the predicted
metal-hydride species (n = −1, M = Cr(0), Mo(0), W(0); n = 0, Mn(I),
Re(I); n = 1, M = Fe(II), Ru(II); n = 2, M = Co(III)). (b) N-alkylation
of aniline with benzyl alcohol with different Mo(0) complex-
es.a,b aReaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), [Mo] (1
mol %), KOtBu (1 equiv), n-hexane (1 mL), seal tube, 130 °C oil bath,
24 h. bGC yields. c2a (0.5 mmol), 1a (0.65 mmol), Mo-1 (2 mol %),
KOtBu (1.1 equiv), n-hexane (0.5 mL), 130 °C oil bath, 24 h, reaction
tube capped with a rubber septum. Molecular structure of Mo-1,
selected bond lengths [Å] and angles [deg]: Mo1−C1 2.028(3), Mo1−
C2 1.994(3), Mo1−C3 1.984(3), Mo1−C4 2.034(3), Mo1−C5
2.260(3), Mo1−C6 2.246(3); C1−Mo1−C4 170.25(13), C2−Mo1−
C6 175.15(11), C3−Mo1−C5 170.71(11). (Thermal ellipsoids are
shown at 50% probability, and C−H atoms are omitted for clarity.)
Based on the computational design results, using the
commercially available Mo(CO)6 and easily accessible bis-
NHCs or NHC-pyridines as sources, five Mo(0) complexes Mo-
1−5 were synthesized with satisfying yields of 46−65% (Figure
1b, synthesis and characterization details in the SI). Their
structures were further characterized by X-ray diffraction (XRD)
analysis of single crystals except for Mo-3. The molecular
structure of Mo-1 shows similar Mo−CNHC bond distances to
the reported bis-BenzNHC-Mo(0).24 After that, these com-
plexes were investigated for the N-alkylation of aniline with
benzyl alcohol as the model reaction in 130 °C. The designed
bis-NHC-Mo(0) complex Mo-1 was found more active than
pyridyl−NHC-Mo(0) (Mo-4) or picolyl−NHC-Mo(0) (Mo-
5), which emphasizes the important donation effect of the NHC
ligand, after considering both the σ donation and the π back-
donation20b via Charge Decomposition Analysis (section 8.3 in
the SI). Note that, the larger substituent −iPr (Mo-2) or −nBu
(Mo-3) on the NHC ligand did not improve the yield.19
Therefore, Mo-1 was chosen as the precatalyst for the N-
alkylation of anilines with alcohols, and the optimal reaction
conditions were established when 2 mol % Mo-1, 1.3 equiv of
alcohols, 1.1 equiv of KOtBu, and 0.5 mL of n-hexane solvent
were used. For details of the conditions’ screenings, see Tables
S1−S9.
(3t), n-hexanol (3u), and n-octanol (3v) were verified to be
reactive, with moderate yields (45−55%). However, when
alcohols with shortened carbon chains (methanol, ethanol) were
tested, no obvious products were detected. Note that, when
halide-substituted benzyl alcohols were investigated, various
amounts of side-product 3a were detected. This dehalogenation
probably happened because of the strongly basic environment
and high temperature, similar to previously observed phenom-
ena.25 The fluoro benzyl alcohol was almost all transferred to 3a.
Chloro benzyl alcohols 1e furnished 37% chloro-product (3e)
and 44% 3a. para- and meta-Chlorobenzyl alcohols resulted in
74% and 75% chloro-product (3f−g), as well as 10% 3a. meta-
and para-Bromobenzyl alcohols produced 51−64% bromo-
product (3h−i), along with 11−24% 3a. Surprisingly, 70% meta-
trifluoromethyl product (3j) was exclusively obtained with the
−CF3 electron-withdrawing group.
The scopes of alcohols were first explored (Figure 2). The
electron-donating groups −Me (3b−d), −OMe (3k), and
−SMe (3l) led to good yields of 76−92%, and the substrates
with conjugated aromatic or bulky substituted groups like
naphthalene (3m and 3n), diphenyl (3q), and benzyloxy (3r)
reacted smoothly with yields of 85−89%. Heteroaromatic
alcohols like pyridine derivative 3o and thiophene derivative
3p slightly decreased in yields (61−63%). Besides, several
aliphatic alcohols like cyclohexanol methanol (3s), n-butanol
Compared with primary alcohols, the N-alkylations of anilines
with secondary alcohols were reported much less, mainly due to
the steric hindrance.26 Gratifyingly, Mo-1 was found capable of
realizing the N-alkylation of anilines with secondary alcohols.
Diphenylmethanol and its methyl and methoxy derivatives were
10378
ACS Catal. 2021, 11, 10377−10382