Zinc Hydride Catalyzed Chemoselective Hydroboration of Isocyanates: Amide Bond Formation and C=O Bond Cleavage

Article abstract of DOI:10.1002/anie.202100375

Herein, a remarkable conjugated bis-guanidinate (CBG) supported zinc hydride, [{LZnH}₂; L={(ArHN)(ArN)?C=N?C=(NAr)(NHAr); Ar=2,6-Et₂-C₆H₃}] (I) catalyzed partial reduction of heteroallenes via hydroboration is r

Full text of DOI:10.1002/anie.202100375

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How to cite: Angew. Chem. Int. Ed. 2021, 60, 11991–12000
International Edition: doi.org/10.1002/anie.202100375
German Edition: doi.org/10.1002/ange.202100375
Hydroboration
Zinc Hydride Catalyzed Chemoselective Hydroboration of
=
Isocyanates: Amide Bond Formation and C O Bond Cleavage
Rajata Kumar Sahoo, Nabin Sarkar, and Sharanappa Nembenna*
Dedicated to Professor Herbert W. Roesky on the occasion of his 85th birthday
Abstract: Herein, a remarkable conjugated bis-guanidinate
work, there were reports on amide synthesis by Grignard or
[
9]
(
(
CBG) supported zinc hydride, [{LZnH} ; L = {(ArHN)-
other metal reagents and isocyanatesꢀ reaction.
Despite the tremendous work on the metal-catalyzed
2
ArN)ÀC=NÀC=(NAr)(NHAr); Ar = 2,6-Et -C H }] (I) cata-
2
6
3
[10]
lyzed partial reduction of heteroallenes via hydroboration is
reported. A large number of aryl and alkyl isocyanates,
including electron-donating and withdrawing groups, undergo
reduction to obtain selectively N-boryl formamide, bis(boryl)
hemiaminal and N-boryl methyl amine products. The com-
pound I effectively catalyzes the chemoselective reduction of
various isocyanates, in which the construction of the amide
bond occurs. Isocyanates undergo a deoxygenation hydro-
boration reaction, in which the C=O bond cleaves, leading to
hydroboration of unsaturated organic molecules, including
[11]
[12]
heteroallenes such as carbon dioxide and carbodiimides,
there have been no reports of hydroboration of isocyanates to
N-boryl formamides (see below). Nonetheless, to the best of
our knowledge, there have been very few reports on selective
[
13]
monohydrosilylation of isocyanates to N-silyl formamide
[
14]
and hydrogenation of isocyanates to formamides.
N-methyl amines are key intermediates in the production
of fine chemicals, dyes, and natural products. Typically, the
[15]
N-boryl methyl amines. Several functionalities such as nitro,
cyano, halide, and alkene groups are well-tolerated. Further-
more, a series of kinetic, control experiments and structurally
characterized intermediates suggest that the zinc hydride
species are responsible for all reduction steps and breaking
the C=O bond.
selective N-alkylation of primary amines utilizing CH I and
3
(CH ) SO is challenging, and usually, over methylation
3
2
4
occurs. Other methods are the metal-catalyzed reduction of
[
16]
CO2 surrogates
hols.
and direct amine alkylation with alco-
[17]
However, these methods suffer from the use of
hazardous chemicals and harsh reaction conditions.
Rueping et al. have shown the magnesium catalyzed
[
18]
Introduction
hydroboration of formamide to N- methyl amine product.
In 2015, Beller and co-workers reported commercially
Isocyanates are cheaper and commercially available feed-
stocks that are very useful in numerous organic transforma-
available Karstadtꢀs complex/2,2’:6’,2’’-terpyridine (tpy) cata-
[
19]
lyzed reductive methylation of amines with carbonates. In
2009, Zhang et al. reported the metal-free reduction of
isocyanates to N-methyl amine using a Ph SiH /B(C F )
5 3
[
1]
tions. These are essential precursors for the synthesis of
[2]
extremely important amides. In particular, formamides are
necessary starting materials to produce useful heterocycles,
2
2
6
[
20]
catalytic system. Besides, there have been reports on the
reduction of isocyanates by using stoichiometric amounts of
[3]
bioactive compounds, and drugs. Generally, these forma-
mides can be accessed using formylating agents such as formic
acid, formaldehyde, formate, chloral, and carbon dioxide,
[
21]
metal reagents.
As far as metal-catalyzed reduction of isocyanates is
concerned, as shown in Figure 1, the ideal catalyst for the
desired transformations should possess few significant fea-
tures: a) Partial (chemoselective) reduction of isocyanates via
hydroboration, the formation of N-boryl formamide; b) re-
duction of isocyanates without cleavage of a C=O bond, N-,
O- bis(boryl) hemiaminal; c) deoxygenated hydroboration of
isocyanates that can lead to the formation of N-boryl methyl
amines in which cleavage of C=O bond should occur.
[
4]
thereby producing a considerable waste. Conventional
methods for amide bond creation are based on CÀN bond-
forming strategies utilizing carboxylic acid derivatives and
[
5]
amines. Formamides can be produced easily by the direct
coupling of methanol with amines using organic or inorganic
[6]
supported metal catalysts (CÀN bond formation). Also, the
recent trend of making amides involves metal-catalyzed CÀC
[
7]
coupling with isocyanates.
Pace and co-workers reported the in situ generated
In this context, Okuda group reported magnesium cata-
tert
Schwartz reagent (Cp ZrClH) mediated chemoselective re-
lyzed dihydroboration of Butyl isocyanate with HBpin to
2
[2a,8]
[22]
duction of isocyanates to formamides.
Before this elegant
N-, O-bis (boryl) hemiaminal. The metal-catalyzed deoxy-
[
23]
genated reduction of amides to amines is known, however
as far as hydrodeoxygenation (HDO) of isocyanates is
concerned, there are only three examples, including recently
[
*] R. K. Sahoo, N. Sarkar, Dr. S. Nembenna
School of Chemical Sciences, National Institute of Science Education
and Research (NISER), Homi Bhabha National Institute (HBNI)
Bhubaneswar, 752050 (India)
[24]
published two patents and one research paper. In 2017, Hill
and co-workers reported magnesium catalyzed hydroboration
[
25]
of isocyanates to N-boryl methyl amines.
The authors
E-mail: snembenna@niser.ac.in
observed N-borylated formamide and N-,O-bis(boryl) hemi-
aminal species as intermediates during the reductive catalysis.
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202100375.
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Table 1: Optimization of zinc hydride catalyzed hydroboration of p-tolyl
[a]
isocyanate.
[b]
Entry
Cat. [mol%]
Solvent
t [h]
Yield [%]
1
2
3
4
5
6
7
8
9
0
10
8
5
3
2
0.5
0.25
2
2
2
2
neat
neat
neat
neat
neat
neat
neat
neat
2
6
4
3
2
2
1
1
2
2
2
2
3
>99
>99
>99
>99
>99
>99
98
>99
>99
>99
>99
benzene
toluene
THF
1
1
1
0
1
2
acetonitrile
[
a] Reaction conditions: p-tolyl isocyanate (0.3 mmol, 1.0 equiv), pina-
colborane (0.3 mmol, 1.0 equiv), catalyst I (2 mol%, 8.0 mg), 2 h at rt
1
under N . [b] Yield was calculated by H NMR spectroscopy based on
2
isocyanate consumption and identified the NCHO signal at 8.93 ppm
confirmed the product.
Moreover, the same reaction was performed in solvents such
as benzene, toluene, THF, and acetonitrile by using a 2 mol%
catalyst; in all cases, we observed the formation of the desired
product in a quantitative yield. A negligible conversion (ca.
3%) was noticed in the absence of catalyst I, displaying that
zinc hydride complex is necessary for isocyanatesꢀ hydro-
boration. Next, we investigated the substrate scope of this zinc
catalyzed organoisocyanates hydroboration reaction with
Figure 1. Production of formamides and N-methyl amines from isocya-
nates.
The catalytic application of molecular zinc hydrides in
[26]
homogenous catalysis has advanced rapidly in recent years.
More recently, we developed a new b-diketiminato analogue,
conjugated bis-guanidinate(CBG) stabilized zinc hydride
complex,
NAr)(NHAr); Ar= 2,6-Et -C H }] (I) and used as a catalyst
[{LZnH}2;
L = {(ArHN)(ArN)ÀC=NÀC= favorable reaction conditions. A wide range of aryl mono
(
and diisocyanate and cyclic and acyclic (long-chain) alkyl
isocyanates have been studied. All reactions went to com-
pletion within 4 h to afford quantitative yield (> 99%)
selective monohydroborated product, N-boryl formamide.
The CBG zinc hydride proved to be a prototype chemo-
selective catalyst for synthesizing formamides from isocya-
nates. The various aryl mono isocyanates, including electron-
donating (1a–1h) and withdrawing groups (1i–1o), were
quantitatively converted into corresponding N-boryl forma-
mide products (2a–2h and 2i–2o). 4-Biphenyllyl and 1-
Napthyl isocyanates were also fully converted into corre-
sponding N-boryl formamides (2p and 2q). A more difficult
substrate, 1,4-phenylene diisocyanate, could be converted
into a quantitative yield of 1,4-phenylene di-N-boryl forma-
mide (2r). It is quite challenging due to the selective N-boryl
formylation of diisocyanates vs. monoisocyanates.
2
6
3
for hydrosilylation and hydroboration of ketones (for the
synthesis of LH, see the Supporting Information,
[
27]
Scheme S1).
Herein, we report the unprecedented zinc
hydride (I) catalyzed mono hydroboration, that is, partial
reduction of a wide range of aryl and alkyl isocyanates to N-
borylated formamides for the first time. Further, zinc
catalyzed dihydroboration and deoxygenated hydroboration
of isocyanates to afford N-, O-bis(boryl) hemiaminal, and N-
boryl methyl amines, respectively, have been investigated.
Results and Discussion
We began our study by exploring the conditions for the
zinc catalyzed isocyanate monohydroboration reaction (Ta-
ble 1). The reaction of 1:1 stoichiometric amounts of p-tolyl
isocyanate and HBpin with 10 mol% catalyst I in a neat
condition gave quantitative conversion to the monohydrobo-
rated product, N-borylated formamide after 6 h at room
temperature. Decreasing the catalyst loadings from 8 to
Both cyclic and acyclic isocyanates are also transformed
into corresponding N-boryl formamides in quantitative yields
(2s–2z) (Scheme 1). We did not observe any other side
products in these reactions. Interestingly, we observed
excellent chemoselectivity in the presence of other reducible
functionalities such as nitro, cyano, halide, and alkene groups.
2
mol% gave a full conversion within 2 h in neat conditions.
1
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isocyanatesꢀ carbon atom. We calculated turn over number
TON) and turn over frequency (TOF) for one representative
(
example, aryl isocyanate, that is, p-tolyl isocyanate (1c),
showcasing the high efficiency of the catalyst I. The catalytic
performance of catalyst I in the monohydroboration of p-tolyl
À1
isocyanate exhibits TON 400 and TOF 400 h (Table 1,
entry 8).
All N-boryl formamides (2a–2z) were characterized by
1
13
1
11
multinuclear ( H, C{ H}, and B) magnetic resonance and
1
mass spectrometry methods. The H NMR spectra exhibit
a characteristic NCHO peak in the range of 8.55–9.19 ppm.
13
1
The C{ H} NMR spectra of each reveal a signature peak for
the NCHO in the range of 164.4–167.4 ppm. Moreover, the
xyl
compound 2d, N-boryl formamide, was confirmed by
single-crystal X-ray structural analysis (Figure 2, left).
Figure 2. Molecular structures of 2d (left) and 2ee (right). The thermal
ellipsoids are shown at 50% probability, and all the hydrogen atoms
(
2
(
except for H(1) from structure 2d and H(7), H(16), from structure
ee) are deleted for clarity. Selected bond lengths [Š] and angles
deg), For 2d (left): O1–C1 1.2115(13), N1–C1 1.3718(13), N1–B1
1
1
.4446(13), N1–C2 1.4485(12); O1-C1-N1 124.97(10), C1-N1-B1
19.88(9), C1-N1-C2 117.43(8). For 2ee (right): O1–C7 1.2265(17),
N1–C7 1.3443(18), N1–C1 1.4100(17); O1-C7-N1 124.64(13), C7-N1-
C1 125.84(12); O2–C16 1.2327(17), N2–C16 1.3383(18), N2–C10
[33]
1
.4144(17); O2-C16-N2 124.85(13), C16-N2-C10 124.22(12).
Bond parameters are consistent with Hillꢀs only example
of structurally characterized N-Borylated formamide, DippN-
[25]
(
Bpin)HC(O). Four examples of N-boryl formamides have
been performed in 1 mmol scale reactions; moreover, these
N-boryl formamides were hydrolyzed into their correspond-
ing free formamides in 78–86% yields. These formamides
1
13
1
were characterized by H and C{ H} NMR spectra. The
spectral data were well in agreement with those reported in
[28]
Scheme 1. Monohydroboration of isocyanates catalyzed by [LZnH]
complex(I). [a] Reaction conditions: isocyanates (0.3 mmol,
the literature.
Next, compound 2ee was confirmed by
2
[
a]
single-crystal X-ray diffraction analysis. Compound 2ee exists
as a dimer in the solid-state, in which NÀH···O hydrogen
1
2
4
.0 equiv), pinacolborane (0.3 mmol, 1.0 equiv), catalyst I (2 mol%),
h at rt under N for all the isocyanates but in case of 2g stirred for
2
bonds link the molecules into the dimeric structure (Figure 2,
right).
h; 2d, 2 f, and 2u stirred for 15 min; and 2i–2o stirred for 10 min.
1
The yield was calculated by H NMR spectroscopy based on isocyanate
consumption and identified the NCHO signal confirmed the product.
Formamide (2ee, 2 ff, 2mm, 2yy) was isolated as a mixture of s-cis
and s-trans isomers after hydrolysis in methanol. [b] catalyst
The addition of two equivalents of HBpin to either
MesNCO (1 f) or DippNCO (1g) in the presence of a zinc
hydride catalyst 2 mol% at room temperature resulted in N-,
O-bis(boryl) hemiaminal product (Scheme 2). In these cases,
two hydride moieties were added to the electrophilic central
carbon atom of bulky isocyanate, and two Bpin moieties were
attached to both nucleophilic N and O atoms. Further, we
attempted to expand the substrate scope with a few more aryl
and alkyl isocyanate dihydroboration reactions. In all cases,
the mixture of products was observed.
(
(
0.25 mol%, 100 mL from stock solution in THF), p-tolyl isocyanate
0.3 mmol, 1.0 equiv), pinacolborane (0.3 mmol, 1.0 equiv), at rt. [c]
For 2r, pinacolborane (0.6 mmol, 2.0 equiv) was used. [d] For 2u, the
1
yield was determined by H NMR spectroscopy using nitromethane as
the internal standard.
We noticed that isocyanates bearing electron-withdrawing
groups react much faster than those bearing electron-donat-
ing groups, owing to their high electrophilicity of the
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Table 2: Optimization of zinc hydride catalyzed hydroboration of p-tolyl
[a]
isocyanate.
[b]
Entry
Cat. [mol%]
Solvent
t h]
Yield [%]
1
2
3
4
5
6
7
8
9
0
10
8
5
2
2
2
2
2
neat
neat
neat
neat
12
12
12
12
12
12
12
12
12
27
>99
>99
>99
>99
>99
>99
>99
>99
Scheme 2. Dihydroboration of isocyanates catalyzed by [LZnH] com-
plex (I). Reaction conditions: [a] 2,4,6-Trimethylphenyl isocyanate
2
neat
benzene
toluene
THF
(
(
(
(
0.3 mmol, 1.0 equiv), pinacolborane (0.6 mmol, 2.0 equiv), catalyst I
2 mol%), 2 h at rt under N . [b] 2,6-Diisopropylphenyl isocyanate
2
0.3 mmol, 1.0 equiv), pinacolborane (0.66 mmol, 2.2 equiv), catalyst I
acetonitrile
1
2 mol%), 24 h at rt under N . The yield was calculated by H NMR
2
[
a] Reaction conditions: p-tolyl isocyanate (0.3 mmol, 1.0 equiv), pina-
colborane (0.9 mmol, 3.0 equiv), catalyst I (2 mol%, 8.0 mg), 12 h at
08C under N . O(Bpin) is the side product. [b] The yield was calculated
spectroscopy based on isocyanate consumption and identified the
NCH OBpin signal confirmed the product.
2
7
2
2
1
by H NMR spectroscopy based on isocyanate consumption and
identified the NCH signal at 3.07 ppm confirmed the product.
3
As mentioned before, as far as metal-catalyzed hydro-
deoxygenation of isocyanates to N-boryl methyl amines is
concerned, there are only three examples reported.
time than the electron-donating groups. All N-boryl methyl
1
Thus, we decided to investigate the same isocyanatesꢀ
deoxygenated hydroboration with HBpin by using catalyst I.
We chose the same p-tolyl isocyanate as a model substrate for
the deoxygenated hydroboration reaction. The reaction of p-
tolyl isocyanate and HBpin in a 1:3 molar ratio with 10 mol%
catalyst I in neat conditions at 708C temperature for 12 h gave
the exclusively N-boryl methyl amine in a quantitative yield.
A similar reaction conditions in the absence of catalyst I, we
observed the mixture of products. We identified them as N-
boryl formamide, N-, O-bis-(boryl) hemiaminal, and N-boryl
methyl amine in a ratio 24:7:27 along with 42% unreacted p-
tolyl isocyanate. Next, the same reaction was performed
under similar conditions using lower catalyst loadings from 8
to 2 mol%. We noticed the formation of the N-boryl methyl
amine product in a quantitative yield. No change in the yield
was observed when the reactions were carried out in the
solvents such as benzene, THF, toluene, and acetonitrile in
standard reaction conditions (Table 2).
amine products were characterized by multinuclear ( H,
1
3
1
11
C{ H} and B) magnetic resonance and mass spectrometric
techniques. All N-boryl methylamine and side product,
[
29]
bis(boryl)oxide, O(Bpin)2 were characterized by the occur-
rence of a singlet methyl H NMR resonance in the range
1
2.10–3.14 ppm and a singlet resonance in the upfield region,
which corresponds to twenty-four protons of O(Bpin) . The
2
1
3
1
C{ H} NMR spectra exhibit an N-CH in the range of 28–
3
11
38 ppm. The B NMR spectra of each reveal two peaks, one
peak for the N-B resonance at ca. 20.20–24.68, which was
assigned to N-boryl methyl amine product and a byproduct
peak of O(Bpin)2.
The catalytic reactivity was evaluated by in situ monitor-
1
ing ( H NMR spectroscopy) of a reaction of HBpin and p-
Bromophenyl isocyanate (1n) catalyzed by 2 mol% of I at rt
to 708C. Figure 3 demonstrates the reactionꢀs progress over
360 minutes and reveals a successive formation of N-boryl
formamide, N-, O-bis-(boryl) hemiaminal, and N-boryl meth-
yl amine products. In the initial stages of the reaction, the
formation of the N-boryl formamide, 4-BrPh(Bpin)HC(O)
(2n), was confirmed by the the emergence of a downfield
singlet peak at 8.81 ppm at room temperature (Figure 3).
Next, when raised the temperature to 708C, the appear-
ance of characteristic peaks at 3.03 ppm and 5.20 ppm
corresponding to N-borylated methyl amine and N-, O-
(bis)-boryl hemiaminal products and complete disappearance
of 4-BrPhN(Bpin)HC(O) (2n) was noticed. After completing
360 minutes, an exclusively hydrodeoxygenated product (C=
Further, we decided to extend the same isocyanate
substrates with the optimized conditions in hand, utilized
for the monohydroboration reaction. To our pleasure, in all
cases (except 4w), a quantitative conversion of isocyanates
into their related N-borylated methyl amine was noticed (4a–
4
z) (Scheme 3). Like monohydroboration reaction, we ob-
served the tolerance of halide, cyano, nitro, and alkene
functionalities. However, it is worthy to note that a reaction of
4
-cyano phenyl isocyanate treated with 5.0 equiv HBpin in
the presence of the catalyst I at room temperature for 24 h
yielded the solely 4-cyano methyl N-boryl methyl amine
product and the cyano group is untouched. However, the
same reaction was carried out at higher temperatures (708C
and 48 h), both nitrile and NCO groups were reduced. The
O bond cleavage), N-boryl methyl amine, 4-BrPhN(Bpin)Me
(4n), along with O(Bpin) , and no other side products were
2
observed.
Kinetics experiments suggest that the reaction proceeds
through a sequential order of mechanism and give evidence
for primarily formed formamide and hemiaminal re-insertion
into the catalytic cycle for further reduction to N-methyl
amine (Figure 4). The N-methyl amine formation represents
1
6
,4-phenylene diisocyanate (1r) upon treatment with
.0 equiv of HBpin at standard reaction conditions resulted
in a quantitative yield of 4r. It was observed that isocyanates
bearing electron-withdrawing groups require less reaction
1
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a sigmoidal curve akin to previous work on magnesium
mediated hydrodeoxygenation of isocyanates described by
Hill and co-workers.
Most importantly, we have further shown zinc hydride
catalyzed intermolecular chemoselective hydroboration of
isocyanates over alkene, nitrile, carbodiimide, and alkyne
substrates for the partial (monohydroboration) and full
reduction reactions. One equivalent p-chlorophenyl isocya-
nate, 1 equiv p-chloro styrene and HBpin were mixed with
catalyst I (2 mol%) under neat conditions at ambient
temperature for 10 minutes, which afforded the N-borylated
formamide in the quantitative yield in preference to the p-
chlorostyrene. Similarly, at the same reaction conditions, p-
chlorophenyl isocyanate gives the monohydroborated prod-
uct, N-borylated formamide, in a quantitative yield over p-
fluorobenzonitrile. Next, equimolar amounts of 2,6-dimethyl
xyl
phenyl isocyanate and carbodiimide and HBpin were mixed
with catalyst I under solvent-free conditions at room temper-
ature for 15 minutes, which produced the N-borylated for-
mamide over the aryl carbodiimide (Scheme 4).
We further examined the catalytic performance of I in the
intermolecular chemoselective deoxgenative reduction be-
tween isocyanate and alkene or nitrile or alkyne. Thus, one
equivalent of p-chlorophenyl isocyanate, 1.0 equiv p-chloro
styrene and 3.0 equiv HBpin were combined with catalyst I
(2 mol%) under neat conditions at ambient temperature for
2
h, which provided the N-boryl methyl amine in the full
conversion of aryl isocyanate priority the alkene. Likewise, at
similar reaction conditions, p-chlorophenyl isocyanate was
reduced to N-boryl methyl amine in a quantitative yield over
either nitrile or alkyne (Scheme 4).
To understand the zinc catalyzed sequential hydrobora-
tion of isocyanates to N-boryl formamide, bis-
(boryl)hemiaminal, and N-boryl methyl amine products, we
performed some control experiments. The catalyst I treated
with two equivalents of DippNCO in toluene at room
temperature for 1 h led to zinc formamidate complex (II).
In this case, the insertion of Zn-H moiety into the carbonyl of
1
RNCO occurred. The intermediate II was confirmed by H
13
1
and C{ H} NMR, IR and mass spectrometric methods.
1
The H NMR spectrum indicates the formation of zinc
formamidate complex by the disappearance of Zn-H
(4.52 ppm) resonance and appearance of a new characteristic
peak at 7.93 ppm (NCHO), which is well in agreement with
[25]
NacNac magnesium formamidate complex (7.92 ppm). The
13
1
C{ H} NMR spectrum exhibits a peak at 172.2 ppm, assigned
to NCHO. Moreover, the formation of compound II was
confirmed by the HRMS analysis. It is worthy to note that
there have been no reports on structurally characterized
molecular zinc hydride insertion into isocyanates, zinc
formamidinate complexes (vide infra). However, Schulz et al.
Scheme 3. Deoxygenative hydroboration of isocyanates catalyzed by
[
a]
[
LZnH] complex (I) [a] Reaction conditions: isocyanates (0.3 mmol,
2
1
1
.0 equiv), pinacolborane (0.9 mmol, 3.0 equiv), catalyst I (2 mol%),
reported zinc amidinato/formamido complexes by zinc hy-
1
2 h at 708C under N . The yield was calculated by H NMR spectros-
2
[30]
dride reaction with isocyanate.
Parkin and co-workers
copy based on isocyanate consumption and identified the NCH signal
3
reported structurally characterized zinc formate and isocya-
confirmed the product. [b] For 4g, 18 h. [c] For 4k, pinacolborane
[31]
nate complexes.
(
(
5.0 equiv.), neat, rt, 24 h was used. [d] For 4k*, pinacolborane
5.0 equiv.), neat, 708C, 48 h was used. [e] For 4m, rt, 2 h. [f] For 4r,
Next, a 1:1 stoichiometric reaction between zinc forma-
midate complex and HBpin has been carried out in C D in a J
pinacolborane (6.0 equiv.), neat, 708C, 12 h was used. [g] For 4w, the
6
6
1
yield was determined by H NMR spectroscopy using nitromethane as
Young valve NMR tube. An immediate formation of com-
the internal standard.
1
13
1
pounds I and 2g was observed by the H and C{ H} NMR
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1
Figure 3. Stacked H NMR spectra (400 MHz) for the reaction of 4-Bromophenyl isocyanate (1n) (0.3 mmol, 1.0 equiv) and pinacolborane
0.9 mmol, 3.0 equiv), and catalyst I (2 mol%) in [D ]THF. Spectra recorded at different temperature and time intervals between T=258C to 708C
(
8
and t=5 min-360 min, respectively. blue ^ =4-BrPhN(Bpin)HC(O), red
&
=4-BrPhN(Bpin)CH OBpin, green ~ =4-BrPhN(Bpin)CH , *=residuals
2
3
peak of [D ]THF.
8
at 708C for 2 days. We observed the CBG zinc boryloxide
(IV) and N-boryl amine (4g) products by NMR studies
(Scheme 5). Furthermore, the X-ray crystal structures of both
zinc compounds II and IV were determined and are depicted
in Figure 5.
To the best of our knowledge, these are the first examples
of zinc formamidate and zinc boryl oxide, which were
structurally authenticated by X-ray crystallography. Com-
pound IIꢀs solid structure revealed a monomeric due to the
i
steric requirements of one N-Dipp (2,6- Pr -C H ) and two N-
2
6
3
Dep (2,6-Et -C H ) substituents. The CÀO bondꢀs cleavage
2
6
3
evidences CBG zinc boryl oxide formation either from II or
N-,O- bis (boryl)hemiaminal species. Like closely related
Figure 4. The plot of [product] versus time for hydroboration of 4-
BrPhNCO catalyzed by 2 mol% I at rt-708C. blue ^ =4-BrPhN-
structurally characterized nacnac magnesium boryl com-
(
(
Bpin)HC(O), red
Bpin)CH3.
&
=4-BrPhN(Bpin)CH OBpin, green ~ =4-BrPhN-
2
[25,32]
plexes,
zinc boryl oxide compound IV is dimeric.
Based on the above kinetic and control experiments,
a catalytic cycle has been proposed for the zinc mediated
hydroboration of isocyanates to N-boryl formamide, bis-
(boryl)hemiaminal, N-boryl methyl amine products
(Scheme 6). In the first step, a reaction between 1:2 stoichio-
metric amounts CBG zinc hydride (I) and isocyanate
(DippNCO) afforded CBG zinc formamidinate complex
(II). Next, a reaction between intermediate II and HBpin
spectra. Further, a 1:2 stoichiometric reaction between
compound II and HBpin was performed in C D at room
6
6
temperature for 12 h in a J Young valve NMR tube.
We noticed the formation of CBG zinc hydride (I) and bis-
hemiaminal (3b). Furthermore, a 1:2 stoichiometric reaction
between compound II and HBpin has been conducted in C D6
6
1
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Scheme 4. Intermolecular chemoselective hydroboration catalyzed by [LZnH] complex (I).
2
bis(boryl) amine, and regeneration of compound I occurred
by the reaction of Int II and HBpin. Alternatively, the
formation of N-, O-bis(boryl) amine, and I can be accessed by
the direct reaction between int II and two equiv of HBpin in
C D at rt for 12 h. A reaction between N-, O-bis(boryl)
6
6
amine, and catalyst I allowed the formation of N-boryl methyl
amine and CBG zinc boryl oxide, Int IVꢀs establishment.
Moreover, a 1:2 stoichiometric ratio of compound II and
HBpin in C D at 708C resulted in CBG zinc boryl oxide and
6
6
N-boryl methyl amine products. Finally, Int IV reacts HBpin
allowed the regeneration of catalyst I and O(Bpin)2 as
a byproduct and closed the catalytic cycle (Scheme 6).
Conclusion
The zinc-catalyzed exceptional chemoselective reduction
of isocyanates via hydroboration is described for the first
time. A wide range of aryl and cyclic, acyclic, long-chain alkyl
isocyanates have been transformed into the corresponding N-
boryl formamides. Moreover, diisocyanate could be efficient-
ly converted into either di-N-borylformamide or di-N-boryl
methyl amine products. Further, we described an excellent
protocol for the catalytic transformation of isocyanates to
secondary methyl amines through zinc-mediated C=O bond
Scheme 5. Control experiments.
cleavage (hydrodeoxygenation of isocyanates). More impor-
tantly, we have shown intra and intermolecular chemoselec-
tive hydroboration of isocyanates over other various reduci-
ble functionalities. Mechanistic investigations studies indicate
that Zn-H moiety insertion into RN=C=O to afford CBG zinc
afforded the N-boryl formamide and regeneration of a catalyst
I. Further, catalyst I reacts with N-boryl formamide led to the
formation of intermediate III. The appearance of N-, O-
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Figure 5. Molecular structures of II (left) and IV (right). The thermal ellipsoids are shown at 50% probability, and all the hydrogen atoms (except
for H(4), H(5), and H(43) from structure II and H(4), H(5), H(9) and H(10) from structure IV) and ethyl groups have been removed for clarity.
Selected bond lengths [Š] and angles (deg), For II (left): Zn1–O1 2.1732(18), Zn1–N1 1.945(2), Zn1–N2 1.9386(19), Zn1–N6 2.0143(19), Zn1–C43
2
.4210, O1–C43 1.272(3); O1-Zn1-N1 118.27(8), O1-Zn1-N2 113.67 (7), O1-Zn1-N6 63.95(7), O1-Zn1-C43 31.562(1), N1-Zn1-N6 132.47(8), N1-
Zn1-C43 133.101(1), N2-Zn1-N1 97.33(8), N2-Zn1-N6 126.54(8), N2-Zn1-C43 125.296(1), N6-Zn1-C43 32.398(1). For IV (right): Zn1–N1 1.956(3),
Zn1–N2 1.953(3), Zn2–N6 1.959(3), Zn2–N7 1.954(3), Zn1–O1 2.019(3), Zn1–O2 1.954(2), Zn2–O1 1.963(3), Zn2–O2 2.014(2), Zn1–Zn2
2
1
9
.9973(5); N1-Zn1-N2 95.76(12), N6-Zn2-N7 96.33(12), O1-Zn1-O2 82.17(10), O1-Zn1-N1 115.20(11), O1-Zn1-N2 119.70(11), O1-Zn2-N6
25.43(12), O1-Zn2-N7 121.13(11), O2-Zn1-N1 121.64(11), O2-Zn1-N2 124.38(11), O2-Zn2-N6 117.83(12), O2-Zn2-N7 115.75(11), Zn1-O1-Zn2
7.66(11), Zn1-O2-Zn2 98.10(11), B1-O1-Zn1 127.8(2), B2- O2-Zn1 134.0(2), B1-O1-Zn2 134.5(2), B2-O2-Zn2 127.9(2).
[33]
Scheme 6. Proposed mechanism.
formamidinato II product and subsequent addition of Acknowledgements
1
.0 equiv of HBpin, 2.0 equiv of HBpin, and 3.0 equiv of
HBpin to yield outcomes, N-boryl formamide, N-, O-bis-
boryl) hemiaminal, and N-boryl methyl amine, respectively,
via sigma bond metathesis. This is the first report on the
The authors thank the National Institute of Science Educa-
tion and Research (NISER), HBNI, Bhubaneswar, Depart-
ment of Atomic Energy (DAE), Govt. of India. We thank Dr.
Achintya Jana for his kind help to solve the crystal structure
of compound IV.
(
metal-catalyzed synthesis of amides through BÀH bond
activation by using isocyanates as precursors. The catalytic
regeneration of the ZnÀH bond and C=O bond cleavage open
new possibilities for zinc hydrides in catalysis.
1
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Keywords: amides · hydroboration · hydrodeoxygenation ·
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