Rhodium-catalysed addition reaction of aryl- and alkenylboronic acids to isocyanates

Article abstract of DOI:10.1039/b709203b

The addition reaction of aryl- and alkenylboronic acids to isocyanates is catalysed by a rhodium(i) complex, affording secondary amides under mild conditions. The Royal Society of Chemistry.

Full text of DOI:10.1039/b709203b

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Rhodium-catalysed addition reaction of aryl- and alkenylboronic acids
to isocyanates{
Tomoya Miura, Yusuke Takahashi and Masahiro Murakami*
Received (in Cambridge, UK) 18th June 2007, Accepted 10th July 2007
First published as an Advance Article on the web 2nd August 2007
DOI: 10.1039/b709203b
The use of three equivalents of 2a improved the yield of 3aa to
The addition reaction of aryl- and alkenylboronic acids to
isocyanates is catalysed by a rhodium(I) complex, affording
secondary amides under mild conditions.
82%.
The rhodium-catalysed addition reaction of organoboron reagents
to electrophilic organic compounds is attracting increasing
attention as a useful method for carbon–carbon bond formation
in organic synthesis.1 Organorhodium(I) species, generated by
transmetalation between boron and rhodium, are considerably
less polar nucleophiles than conventional organometallic reagents
like Grignard and organolithium reagents. Nevertheless,
organorhodium(I) species are reactive enough to add inter-
molecularly to various unsaturated compounds. Polar unsaturated
electrophiles such as aldehydes,2 imines3 and nitriles4 are
supposedly less reactive toward organorhodium(I) species than
less polar unsaturated substrates like electron-deficient alkenes5
and alkynes,6 although few experimental results are available for a
direct comparison of the reactivities of these electrophiles. Mori
demonstrated that, despite their highly polar nature, isocyanates
can act as good electrophilic substrates in reactions with
organorhodium(I) species generated from organotin reagents by
transmetalation.7 As precursors to organorhodium(I) species,
organoboron reagents, organoboronic acids in particular, possess
advantages over organotin reagents in terms of commercial
availability, toxicity and ease of post-treatment.8 In addition,
organoboron reagents are readily available with a wide variety of
functional groups due to the recent development of direct
preparative methods that do not require the use of highly reactive
Grignard and organolithium reagents.9 We now report the
rhodium-catalysed addition reaction of aryl- and alkenylboronic
acids to isocyanates, forming secondary amides under mild
conditions.10
ð1Þ
A potential reaction pathway is depicted in Scheme 1. Initially,
phenylrhodium(I) species A is generated by transmetalation
between phenylboronic acid (2a) and rhodium(I).11 The phenyl-
rhodium(I) species A then adds to the isocyanato group of 1a to
form O-bound and/or N-bound rhodium(I) complex (B and/or C).
Protonolysis with 2a releases the product 3aa together with
rhodium(I) boronate, which regenerates A through b-aryl elimina-
tion.12 The use of other organoboron reagents such as phenylbor-
oxine (2a9) and 5,5-dimethyl-2-phenyl-1,3,2-dioxaborinane in place
of 2a gave 3aa in lower yield under the same reaction conditions.
For comparison, 4-CH3C6H4SnBu3 (3.0 equiv.) was reacted
with 1a at room temperature in the presence and absence of
phenol.13 No adduct 3ab was produced in either case. It is likely
that the rate of the entire addition reaction largely depends on the
rate of transmetalation generating the arylrhodium(I) species A.
Various combinations of isocyanates 1 and organoboronic acids
2 were examined for the synthesis of amides 3 (Table 1).{ The
catalytic process worked well with electron-rich arylboronic acids
2b–2d (entries 1–3). Even the hindered o-tolylboronic acid (2c)
afforded the corresponding amide 3ac in high yield. On the other
hand, electron-poor arylboronic acids 2e and 2f were less reactive
(entries 4 and 5). 3-Thienylboronic acid (2g) and the alkenyl-
boronic acids 2h and 2i also participated in the addition reaction
(entries 6–8).
Phenyl isocyanate (1a, 1.0 equiv.) was treated with phenyl-
boronic acid (2a, 1.5 equiv.) in the presence of [Rh(OH)(cod)]2
(5 mol% Rh, cod 5 cycloocta-1,5-diene) in THF (0.1 M) at room
temperature under an argon atmosphere [eqn (1)]. Unlike the
case of organotin reagents, which required heating at 70 uC,7 the
addition reaction of 2a to 1a proceeded smoothly at room
temperature to consume 2a in 12 h. However, hydrolysis of
intermediate phenylrhodium(I) species A (vide infra) occurred
concomitantly, and chromatographic isolation on silica gel
afforded the secondary amide 3aa in only moderate yield (49%).
Three regio-isomeric tolyl isocyanates 1b–1d all afforded the
corresponding adducts 3ba–3da in good yield (entries 9–11). A
Department of Synthetic Chemistry and Biological Chemistry, Kyoto
University, Katsura, Kyoto, 615-8510, Japan.
E-mail: murakami@sbchem.kyoto-u.ac; Fax: +81 75 383 2748;
Tel: +81 75 383 2747
{ Electronic supplementary information (ESI) available: General experi-
mental information and spectral data. See DOI: 10.1039/b709203b
Scheme 1 A plausible mechanism for the catalysed addition reaction.
Chem. Commun., 2007, 3577–3579 | 3577
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Table 1 Rh(I)-catalysed reaction of isocyanates 1 (R1NCO) with
organoboronic acids 2 (R2B(OH)2)a
Entry 1 R1
2
R2
3
Yield (%)b
1
2
3
4
5
6
7
8
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
2b 4-MeC6H4
2c 2-MeC6H4
2d 3-MeOC6H4
2e 3-BrC6H4
2f 3-ClC6H4
2g 3-Thienyl
2h b-Styryl
3ab 88
3ac 90
3ad 84
3ae 58
3af 21
3ag 94
3ah 91
(2)
2i (E)-Pent-1-enyl 3ai 73
9
1b 4-MeC6H4
1c 3-MeC6H4
1d 2-MeC6H4
1e 4-MeOC6H4
1f 4-ClC6H4
1g 4-EtO2CC6H4
1h 3-O2NC6H4
1i 2-(1-Pent-1-enyl)-C6H4 2a Ph
1j n-Hexyl
1k Cyclohexyl
1k Cyclohexyl
2a Ph
2a Ph
2a Ph
2a Ph
2a Ph
2a9 Ph (R2BO)3
2a9 Ph (R2BO)3
3ba 84
3ca 84
3da 68
3ea 78
3fa 76
3ga 83c
3ha 74c
3ia 90
3ja 75
3ka 62
3ka 93c
10
11
12
13
14
15
16
17
18
19
a
(3)
2a Ph
2a Ph
2a9 Ph (R2BO)3
1 (0.2 mmol), 2 (0.6 mmol), [Rh(OH)(cod)]2 (5 mol% Rh) in THF
(0.1 M) at room temperature for 12 h under Ar unless otherwise
noted.
b
Isolated yields of products with .95% purity after
c
18032040 from the Ministry of Education, Culture, Sports, Science
and Technology, Japan.
chromatography. 1 (0.2 mmol), phenylboroxine (2a9, 0.2 mmol,
3.0 equiv. of B), [Rh(OH)(cod)]2 (5 mol% Rh) in dioxane (0.1 M) at
100 uC for 12 h under Ar.
Notes and references
{ General procedure: To an oven-dried flask was added [Rh(OH)(cod)]2
(2.3 mg, 5.0 mmol, 5 mol% Rh), organoboronic acid 2 (0.60 mmol,
3.0 equiv.) and a solution of isocyanate 1 (0.20 mmol, 1.0 equiv.) in dry
THF (2.0 mL). The reaction mixture was stirred at room temperature for
12 h under an argon atmosphere, and then quenched with addition of
water (2.0 mL). The resulting aqueous solution was extracted with ethyl
acetate (4 6 10 mL). The combined extracts were washed with brine and
dried over MgSO4. The solvent was removed under reduced pressure and
the residue was purified by preparative thin-layer chromatography
(chloroform–ethyl acetate 20 : 1 or 10 : 1) to give the corresponding
amide 3.
wide range of substituents were tolerated on the aryl group of 1
(entries 12–16). Substrates 1g and 1h possessing electron-with-
drawing ester and nitro groups on the benzene rings, respectively,
were reacted with phenylboroxine (2a9) in place of 2a in order to
suppress a potentially competitive hydrolysis–decarboxylation
pathway that would generate the corresponding aniline derivatives
(entries 14 and 15). The successful results obtained with 1g and 1h
demonstrated that ester and nitro groups, which would be affected
by Grignard reagents, are compatible with the present reaction
conditions. In addition, alkyl isocyanate 1j and 1k also reacted
with either 2a or 2a9 (entries 17–19).
1 For reviews, see: (a) K. Fagnou and M. Lautens, Chem. Rev., 2003, 103,
169; (b) T. Hayashi and K. Yamasaki, Chem. Rev., 2003, 103, 2829; (c)
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We next carried out the following competitive experiments to
directly assess the reactivity of a phenylrhodium(I) species toward
an isocyanate, an electron-deficient alkene and an aldehyde. Thus,
a mixture of phenyl isocyanate (1a, 1.0 equiv.) and cyclohex-2-en-
1-one (4, 1.0 equiv.) was treated with phenylboronic acid (2a,
2.0 equiv.) in the presence of [Rh(OH)(cod)]2 (5 mol% Rh). After
the reaction mixture was stirred for 12 h at room temperature, the
corresponding adducts 3aa and 5 were isolated in 73% and 15%
yields, respectively [eqn (2)]. Contrary to our expectation on the
basis of functional group polarity, the isocyanate 1a was a better
acceptor for phenylrhodium(I) species than cyclohex-2-en-1-one
(4). An analogous competition experiment using 1a and benzal-
dehyde (6) resulted in the formation of 3aa in 68% yield and a trace
of 7 [less than 5% yield, eqn (3)]. These results indicate that the
electrophilic reactivities toward phenylrhodium(I) nucleophiles are
approximately isocyanate . electron-deficient alkene & aldehyde.
In summary, the rhodium-catalysed addition reaction of
organoboronic acids to isocyanates provides a convenient method
for the construction of secondary amides. Further synthetic
applications of the present reaction are currently under way.
This work was supported in part by a Grant-in-Aid for Young
Scientists (B) 18750084 and Scientific Research on Priority Areas
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13 Phenol was an effective additive in the rhodium-catalysed addition
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Chem. Commun., 2007, 3577–3579 | 3579