Preparation of imides via the palladium-catalyzed coupling reaction of organoborons with methyl N -[methoxy(methylthio)methylene]carbamate as a one-carbon elongation reaction

Article abstract of DOI:10.1021/ol303062a

The preparation of imides via the palladium-catalyzed coupling reaction as a one-carbon elongation reaction is described. The palladium-catalyzed coupling reaction of aryl-, alkyl-, and alkenylborons with N-[methoxy(methylthio) methylene]carbamate in the presence of Cu(I) thiophene-2-carboxylate (CuTC) affords imino ethers that are converted to the corresponding imides by acidic hydrolysis in high yield. The imino ethers are also useful for preparing the corresponding ester without using carbon monoxide.

Full text of DOI:10.1021/ol303062a

ORGANIC
LETTERS
2012
Vol. 14, No. 24
6294–6297
Preparation of Imides via the
Palladium-Catalyzed Coupling
Reaction of Organoborons with Methyl
N‑[Methoxy(methylthio)methylene]-
carbamate as a One-Carbon Elongation
Reaction
Takuhei Tomizawa, Kohei Orimoto, Takashi Niwa, and Masahisa Nakada*
Department of Chemistry and Biochemistry, School of Advanced Science and
Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan
mnakada@waseda.jp
Received November 7, 2012
ABSTRACT
The preparation of imides via the palladium-catalyzed coupling reaction as a one-carbon elongation reaction is described. The palladium-
catalyzed coupling reaction of aryl-, alkyl-, and alkenylborons with N-[methoxy(methylthio)methylene]carbamate in the presence of Cu(I)
thiophene-2-carboxylate (CuTC) affords imino ethers that are converted to the corresponding imides by acidic hydrolysis in high yield. The imino
ethers are also useful for preparing the corresponding ester without using carbon monoxide.
Imides are diacyl derivatives of ammonia or primary
amines or, in a broadsense, functional groups consisting of
two carbonyl groups bound to nitrogen. Recently, imides
have been utilized in the catalytic asymmetric conjugate
additions of hydrazoic acid,1a cyanide,1b amine,1c
malononitrile,1d oxime,1e arylthiol,1f and activated methy-
lene compounds1g,h along with their transformations,1
suggesting their potential utility in organic synthesis.
Usually, imides are prepared by condensation reactions
of amides with acylating reagents (A)2 or by reaction of
activated carboxylic acid derivatives with amides (B).3
Therefore, these methods require the corresponding car-
boxylic acids or their derivatives as starting materials,
thereby limiting the variation of their syntheses.
Scheme 1
(1) (a) Myers, J. K.; Jacobsen, E. N. J. Am. Chem. Soc. 1999, 121,
8959. (b) Sammis, G. M.; Jacobsen, E. N. J. Am. Chem. Soc. 2003, 125,
4442. (c) Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2003, 125,
11204. (d) Sibi, M. P.; Prabagaran, N.; Ghorpade, S. G.; Jasperse, C. P.
J. Am. Chem. Soc. 2003, 125, 11796. (e) Vanderwal, C. D.; Jacobsen,
E. N. J. Am. Chem. Soc. 2004, 126, 14724. (f) Li, B.-J.; Jiang, L.; Liu, M.;
Chen, Y.-C.; Ding, L.-S.; Wu, Y. Synlett 2005, 603. (g) Hoashi, Y.;
Okino, T.; Takemoto, Y. Angew. Chem., Int. Ed. 2005, 44, 4032. (h)
Inokuma, T.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc. 2006, 128,
9413.
(2) For example, see: Yao, L.; Pitta, B.; Ravikumar, P. C.; Purzycki,
M.; Fleming, F. F. J. Org. Chem. 2012, 77, 3651.
(3) For example, see: DeNinno, M. P.; Eller, C.; Etienne, J. B. J. Org.
Chem. 2001, 66, 6988.
r
10.1021/ol303062a
Published on Web 12/12/2012
2012 American Chemical Society

Liebeskind and Srogl reported a palladium-catalyzed
CÀC cross-coupling reaction of thioesters with boronic
acids in the presence of Cu(I) thiophene-2-carboxylate
(CuTC) that affords ketones under neutral conditions.4
This CÀC bond-forming reaction has been extended to the
cross-coupling reactions between a variety of organosulfur
and organometallic reagents. Most boronic acids and
organosulfur compounds are air- and moisture-stable
and have low toxicity. Therefore, the cross-coupling reac-
tions with these reagents are highly attractive and useful
for the organic syntheses of complex natural products.
Palladium-catalyzed one-carbon elongation reactions of
organoborons have been reported.5 However, most of the
reactions use toxic carbon monoxide, and to the best of our
knowledge, the preparation of imides via the Pd-catalyzed
coupling reaction has not yet been reported. We herein
report a preparation method of imides via the Pd-catalyzed
coupling reactions of organoboranes (C, Scheme 1).
We first attempted the Pd-catalyzed coupling reaction of
phenylboronic acid 1a with imide 2a (Scheme 2) because
this reaction was thought to provide straightforward
access to imides. The reaction was carried out under the
conditions that have been used in the LiebeskindÀSrogl
coupling reaction.
nitrogen. Compound 4 was prepared in a one-pot manner
according to the known procedure6 as shown in Scheme 3.
That is, the reaction of methyl chloroformate with potas-
sium isothiocyanate was carried out in THF to afford
isothiocyanate, which was subjected to the reaction with
methanol, followed by S-methylation with dimethyl sul-
fate to afford 4 as a white crystal.
Scheme 3
Table 1. Optimization of the Pd-Catalyzed Coupling Reaction
of Phenylboronic Acid 1a with 4
Pd
ligand
yield
(%)a
However, the coupled product 3a was not obtained and
only 2a was consumed. This result suggested the possibility
of the occurrence of β-elimination of the acylpalladium
intermediate that was formed by the reaction of 2a with
palladium(0). Therefore, we attempted the reaction of 1a
with 2b, which has a MOM group on the nitrogen atom,
but no reactions occurred.
entry
solvent
THF
(10 mol %)
(mol %)
1
2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
À
91
80
69
50
42
42
70
76
81
70
1,4-dioxane
DMF
À
3
À
4
CH3CN
toluene
(CH2Cl)2
THF
À
5
À
6
À
7
PPh3 (20)
PPh3 (30)
TFPb (30)
AsPh3 (30)
8
THF
9
THF
Scheme 2
10
THF
a Isolated yields. b TFP = tris(2-furyl)phosphine.
With 4 in hand, its Pd-catalyzed coupling reaction
with arylboronic acid 1a was examined (Table 1). Because
the coupling reaction did not proceed at rt, all the reac-
tions (entries 1À10) were carried out at 50 °C using 4
(1.1 equiv) in the presence of CuTC (copper(I) thiophene-
2-carboxylate) (3.0 equiv), which is the additive usually
used in the LiebeskindÀSrogl coupling reaction. The reac-
tion with a catalytic amount of Pd(PPh3)4 in THF afforded
the coupled product 5a in 91% yield. The same reaction
was carried out in different solvents, but the yield was not
improved (entries 2À6). Palladium catalysts other than
Pd(PPh3)4 werealsoexamined(entries7À10); however, the
best results were obtained when using Pd(PPh3)4.
The negatively charged boronate under the basic con-
ditions can undergo the additionÀelimination sequence
to form the same product without palladium. However,
the reaction of 1a in the absence of a Pd reagent afforded
no products, suggesting that this coupling reaction is a
Pd-catalyzed reaction.
We next examined the coupling reaction of 1a with
methyl N-[methoxy(methylthio)methylene]carbamate (4)
because 4 has a methylthio group attached at the sp2
carbon of a CÀN double bond and no H-atom on the
(4) (a) Liebeskind, L. S.; Srogl, J. J. Am. Chem. Soc. 2000, 122, 11260.
(b) Yu, Y.; Liebeskind, L. S. J. Org. Chem. 2004, 69, 3554. (c)
Prokopcov, H.; Kappe, C. O. Angew. Chem., Int. Ed. 2009, 48, 2276.
(5) (a) Miyaura, N.; Suzuki, A. Chem. Lett. 1981, 879. (b) Satoh, M.;
Miyaura, N.; Suzuki, A. Chem. Lett. 1986, 1329. (c) Ohe, T.; Ohe, K.;
Uemura, S.; Sugita, N. J. Organomet. Chem. 1988, 344, C5. (d) Cho,
C. S.; Ohe, T.; Uemura, S. J. Organomet. Chem. 1995, 496, 221. (e) Duan,
Y.-Z.; Deng, M.-Z. Synlett 2005, 355. (f) Yamamoto, Y.; Hattori, K.;
Ishii, J.-I.; Nishiyama, H.; Itoh, K. Chem. Commun. 2005, 4438. (g)
Yamamoto, Y. Adv. Synth. Catal. 2010, 352, 478. (h) Liu, Q.; Li, G.; He,
J.; Liu, J.; Li, P.; Lei, A. Angew. Chem., Int. Ed. 2010, 49, 3371. (i) Li, M.;
Wang, C.; Fang, P.; Ge, H. Chem. Commun. 2011, 47, 6587. For the
transition-metal-catalyzed carboxylation of organoborons with carbon-
dioxide, see: Rh: (j) Ukai, K.; Aoki, M.; Takaya, J.; Iwasawa, N. J. Am.
Chem. Soc. 2006, 128, 8706. (k) Takaya, J.; Tadami, S.; Ukai, K.;
Iwasawa, N. Org. Lett. 2008, 10, 2697. Cu: (l) Ohishi, T.; Nishiura,
M.; Hou, Z. Angew. Chem., Int. Ed. 2008, 47, 5792.
(6) Cohen, F.; Overman, L. E. J. Am. Chem. Soc. 2006, 128, 2594.
Org. Lett., Vol. 14, No. 24, 2012
6295

Table 2. Preparation of Imides 6aÀf via the Pd-Catalyzed
Coupling Reactions of Arylboronic Acids 1aÀf (1.0 equiv) with
4 (1.1 equiv)
Table 3. Pd-Catalyzed Coupling Reactions of Phenylboronic
Acids 1aÀf (2.0 equiv) with 4 (1.0 equiv)
a Isolated yields.
9-BBN. Therefore, the Pd-catalyzed coupling reactions of
some B-alkyl 9-BBN reagents with 4 were carried out. That
is, alkenes 7aÀe were subjected to the reaction with 9-BBN
(1.0 equiv) to form B-alkyl 9-BBN reagents, which were
used for the coupling reactions with 4 (1.1 equiv) in the
presence of CuTC (3.0 equiv), Pd(PPh3)4 (10 mol %), and
cesium carbonate (5.0 equiv).
Use of cesium carbonate was necessary in the reaction of
B-alkyl 9-BBN reagents to attain good yields.4,7 The over-
all yields of the three steps, hydroboration of alkenes 7aÀe
with 9-BBN, the palladium-catalyzed coupling reaction of
B-alkyl 9-BBN reagents with 4, and subsequent acid
hydrolysis, are all summarized in Table 4. All alkenes
(7aÀe) were successfully converted to the corresponding
imides via the three steps (Table 4, entries 1À5). The
overall yield is high, ranging from 76% to 83%. Thus,
the average yield per step is over 90%, indicating that the
three-step sequence could be a practical protocol for
preparing alkyl imides.
The Pd-catalyzed coupling reactions of alkenylboronic
acids 9a and 9b (1.0 equiv) with 4 (1.1 equiv) also afforded
the corresponding imides under the optimized condi-
tions in Table 1 (Table 5). Although the coupling reac-
tion of 9a required 12 h for completion (entry 1), the acid
hydrolysis following the coupling reactions of 9a and 9b
afforded imides 10a and 10b, respectively, in excellent
yields, indicating that the protocol developed by us
would also be useful for the preparation of R,β-unsaturated
imides.
a Isolated yields.
Hydrolysis of 5a under acidic conditions easily afforded
imide 6a in 97% yield (Table 2, entry 1). Hence, the
coupling reaction of other arylboronic acids 1bÀf with 4
and the following hydrolysis were examined next (Table 2).
The coupling reaction of p-tolylboronic acid 1b with 4
afforded 5b in 97% yield, and its acidic hydrolysis gave 6b
in 95% yield (entry 2). The yields of the coupling reactions
of phenylboronic acids bearing an ester (entry 3) or a
fluoride (entry 5) were slightly lower, probably because
the electron-withdrawing groups on the phenyl group
could reduce the reactivity of the arylboronic acids. The
yield of the reaction of o-tolylboronic acid (entry 4) was
also reduced, possibly owing to the steric bulkiness of the
methyl group at the ortho position. The yield of the
reaction of 2-thienylboronic acid (entry 6) was marginal,
which could be attributed to the deactivation of palladium
or copper by the coordination of the thienyl group.
The Pd-catalyzed coupling reactions of arylboronic
acids 1aÀf (2.0 equiv) with 4 (1.0 equiv) were also exam-
ined (Table 3). The yields of all the reactions were compar-
able (entries 1À3 and 5) to those in Table 2 or better
(entries 4 and 6). Notably, all the reactions required a
prolonged reaction time for completion, though the reason
is unknown.
The Pd-catalyzed coupling reactions of B-alkyl 9-BBN
reagents with thioesters reported by Liebeskind4b and the
successful results above encouraged us to examine the Pd-
catalyzed coupling reaction of B-alkyl 9-BBN reagents
with 4 (Table 4). B-alkyl 9-BBN reagents are easily pre-
pared by hydroboration of the corresponding alkenes with
(7) (a) Miyaura, N.; Ishiyama, T.; Ishikawa, M.; Suzuki, A. Tetra-
hedron Lett. 1986, 27, 6369. (b) Sato, M.; Miyaura, N.; Suzuki, A. Chem.
Lett. 1989, 1405. (c) Oh-e, T.; Miyayra, N.; Suzuki, A. J. Org. Chem.
1993, 58, 2201.
6296
Org. Lett., Vol. 14, No. 24, 2012

Table 4. Preparation of Imides 8aÀe via the Pd-Catalyzed
Coupling Reactions of Prepared B-Alkyl 9-BBN Reagents 7aÀe
with 4
Table 5. Preparation of Imides 10 via the Pd-Catalyzed Cou-
pling Reactions of Alkenylboronic Acids 9a and 9b with 4
a Isolated yields.
Scheme 4
a Isolated yields.
reaction of organostannanes with methyl N-[methoxy-
(methylthio)methylene]carbamate is surmised to give the
same results; hence, it is now under investigation, and the
results will be reported in due course.
Imino ethers are known to be precursors of esters. For
example, imide 5b was converted to the corresponding
methyl ester 11b in 90% yield (Scheme 4). Hence, the Pd-
catalyzed coupling reaction of organoborons with 4 could
be utilized for the preparation of esters.
In summary, we have developed a new preparation
method of imides via the Pd-catalyzed coupling reaction
of organoborons with methyl N-[methoxy(methylthio)-
methylene]carbamate. The method is widely applicable
to aryl-, alkyl-, and alkenylborons, enabling access to a
variety of imides in high to excellent yields. The imino
ethers formed by the Pd-catalyzed coupling reaction
are easily converted to the corresponding imides or esters
under mild acidic conditions. The developed preparation
method comprises a one-carbon elongation that does
not use toxic carbon monoxide. The same Pd-catalyzed
Acknowledgment. This work was financially supported
in part by The Grant-in-Aid for Scientific Research on
Innovative Areas “Organic Synthesis based on Reaction
Integration. Development of New Methods and Creation
of New Substances” (No. 2105).
Supporting Information Available. Experimental pro-
cedures and compound characterization data. This ma-
terial is available free of charge via the Internet at http://
pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 24, 2012
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