Intermolecular hydroamination of allenes with N-unsubstituted carbamates catalyzed by a gold(I) N-heterocyclic carbene complex

Article abstract of DOI:10.1021/ol8010858

(Chemical Equation Presented) Reaction of 2,3-pentadienyl benzoate with benzyl carbamate catalyzed by a 1:1 mixture of (NHC)AuCl and AgOTf in dioxane at 23°C for 5 h led to isolation of (E)-4-(benzyloxycarbonylamino)-2-pentenyl benzoate in 84% yield as a single regio- and diastereomer. Gold(I)-catalyzed hydroamination was effective for a number of N-unsubstituted carbamates and a range of substituted allenes.

Full text of DOI:10.1021/ol8010858

ORGANIC
LETTERS
2008
Vol. 10, No. 14
3157-3159
Intermolecular Hydroamination of
Allenes with N-Unsubstituted
Carbamates Catalyzed by a Gold(I)
N-Heterocyclic Carbene Complex
Robert E. Kinder, Zhibin Zhang, and Ross A. Widenhoefer*
Duke UniVersity, French Family Science Center, Durham, North Carolina 27708-0346
rwidenho@chem.duke.edu
Received May 10, 2008
ABSTRACT
Reaction of 2,3-pentadienyl benzoate with benzyl carbamate catalyzed by a 1:1 mixture of (NHC)AuCl and AgOTf in dioxane at 23 °C for 5 h
led to isolation of (E)-4-(benzyloxycarbonylamino)-2-pentenyl benzoate in 84% yield as a single regio- and diastereomer. Gold(I)-catalyzed
hydroamination was effective for a number of N-unsubstituted carbamates and a range of substituted allenes.
Allylic amines are components of many naturally occurring
and biologically active molecules and are versatile building
blocks for the synthesis of complex nitrogen-containing
molecules. As a result, considerable effort has been directed
toward the development of general and selective methods
for the synthesis of allylic amines.1,2 The transition-metal-
catalyzed addition of the N-H bond of an amine or
carboxamide derivative across the CdC bond of an allene
represents an attractive and atom-economical approach to
the synthesis of allylic amines.3 However, whereas general
and efficient methods for the intramolecular hydroamination
of allenes have been developed,4,5 the intermolecular hy-
droamination of allenes remains problematic, and no methods
are available that effectively employ ammonia or ammonia
(3) The intermolecular hydroamination of 1,3-dienes has also been
investigated as a route to allylic amines: (a) Qin, H.; Yamagiwa, N.;
Matsunaga, S.; Shibasaki, M J. Am. Chem. Soc. 2006, 128, 1611. (b)
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(2) For recent efforts directed toward the synthesis of allylic amines,
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.
10.1021/ol8010858 CCC: $40.75
Published on Web 06/21/2008
2008 American Chemical Society

equivalents as nucleophiles.6,7 Here we describe a general,
regio- and stereoselective gold(I)-catalyzed protocol for the
intermolecular hydroamination of allenes that employs N-
unsubstituted carbamates as ammonia surrogates.
Table 1. Gold(I)-Catalyzed Hydroamination of
3-Methyl-1,2-butadiene (3) with Benzyl Carbamate as a
Function of Supporting Ligand
We have developed an effective protocol for the intramo-
lecular hydroamination of N-γ- and δ-allenyl carbamates
catalyzed by a mixture of the gold phosphine complex
(1)AuCl [1 ) P-t-Bu2-o-biphenyl]5 and AgOTf5 and a
protocol for the intermolecular hydroalkoxylation of allenes
with alcohols catalyzed by a mixture of the gold (NHC)
complex (2)AuCl [2 ) 1,3-bis(2,6-diisopropylphenyl)imi-
dazol-2-ylidine] and AgOTf (Scheme 1).8,9 We therefore
entry
L
convna (%)
1
2
3
4
5
6
1
57
58
47
0
25
96
PCy2-o-biphenyl
PCy2{2[2,5(OMe)2C6H3]C6H4}
PtBu2[2(2NMe2C6H3)C6H4]
P(4MeOC6H4)3
2
Scheme 1
a Conversion determined by GC analysis of the crude reaction mixture
versus hexadecane internal standard.
4a as the exclusive product (Table 1, entry 6). Allylic
carbamate 4a was isolated in 93% yield from the corre-
sponding preparative-scale reaction (Table 2, entry 1).
In addition to benzyl carbamate, 9-fluorenylmethyl car-
bamate and methyl carbamate reacted with 3 in the presence
of (2)AuCl/AgOTf to form N-tertiary allylic carbamates 4b
and 4c, respectively (Table 2, entries 2 and 3). Both the
differentially 1,1-disubstituted allene 5 and trisubstituted
allene 6 underwent intermolecular hydroamination to form
the corresponding N-tertiary allylic carbamates (7 and 8) in
modest yield as single regioisomers (Table 2, entries 4-6).
Whereas hydroamination of the electron-deficient monosub-
stituted allene 9 led to exclusive formation of the N-primary
(E)-allylic carbamate 10 (Table 2, entry 7), hydroamination
of monoalkyl-substituted allene 11 formed a 1:1 mixture of
N-secondary (12a) and N-primary (12b) allylic carbamates
(Table 2, entry 8). 1,3-Disubstituted allenes 13-16 under-
went hydroamination in good yield, with high E-selectivity,
and in the case of differentially substituted allenes 14-16,
with exclusive attack of carbamate at the more electron-rich
allene terminus (Table 2, entries 9-12). Reaction of enan-
tiomericaly enriched allene (S)-15 (76% ee) with benzyl
carbamate led to isolation of racemic 19 in 78% yield. This
outcome is not surprising given the rapid (e10 min)
racemization of (S)-15 under reaction conditions.8 Hydroami-
nation of tetrasubstituted allene 21 formed N-tertiary allylic
carbamate 22 in modest yield (Table 2, entry 13).
targeted (1)AuCl and (2)AuCl as precatalysts for the
intermolecular hydroamination of allenes with N-unsubsti-
tuted carbamates. In an initial experiment, reaction of
3-methyl-1,2-butadiene (3) and benzyl carbamate catalyzed
by a 1:1 mixture of (1)AuCl and AgOTf in dioxane at 23
°C for 24 h led to 57% conversion to form the N-tertiary
allylic carbamate 4a as the exclusive product (Table 1, entry
1). Longer reaction time or employment of related gold
phosphine catalysts led to no significant improvement in
conversion (Table 1, entries 2-5). Conversely, reaction of
3 and benzyl carbamate with a catalytic mixture of (2)AuCl
and AgOTf at 23 °C for 24 h led to 96% conversion to form
(5) Zhang, Z.; Liu, C.; Kinder, R. E.; Han, X.; Qian, H.; Widenhoefer,
R. A. J. Am. Chem. Soc. 2006, 128, 9066
.
(6) (a) Johnson, J. S.; Bergman, R. G. J. Am. Chem. Soc. 2001, 123,
2923. (b) Ayinla, R. O.; Schafer, L. L. Inorg. Chim. Acta 2006, 359, 3097.
(c) Besson, L.; Gore, J.; Cazes, B. Tetrahedron Lett. 1995, 36, 3857. (d)
Nishina, N.; Yamamoto, Y. Angew. Chem., Int. Ed. 2006, 45, 3314. (e)
Nishina, N.; Yamamoto, Y. Synlett 2007, 1767
.
(7) Yamamoto has reported the Pd(0)-catalyzed hydroamination of
allenes with dibenzylamine and sulfonamide, but these transformations were
restricted to monosubstituted aryl allenes and, in the case of TsNH2, led to
formation of mixtures of mono- and bisaddition products: Al-Masum, M.;
Noteworthy is the contrasting regioselectivity of the
(2)AuCl/AgOTf-catalyzed intermolecular hydroamination
and hydroalkoxylation of allenes. While both transformations
favor addition of the nucleophile to the more electron-rich
terminus of differentially 1,3-disubstituted allenes such as
14 and 15, hydroalkoxylation displays much greater sensitiv-
ity to steric hindrance than does hydroamination, leading to
preferential attack of alcohol at the less-substituted terminus
of 1,1-disubstituted allenes such as 3 and trisubstituted
allenes, as opposed to selective attack of carbamate at the
more substituted allene terminus.10
Meguro, M.; Yamamoto, Y. Tetrahedron Lett. 1997, 38, 6071
.
(8) Zhang, Z.; Widenhoefer, R. A. Org. Lett. 2008, 10, 2079
.
(9) For additional examples of intermolecular allene hydrofunctional-
ization, see: (a) Patil, N. T.; Pahadi, N. K.; Yamamoto, Y. Can. J. Chem.
2005, 83, 569. (b) Kim, I. S.; Krische, M. J. Org. Lett. 2008, 10, 513. (c)
Schulz, M.; Teles, J. H. Chem. Abstr. 1997, 127, 121499; (BASF AG),
WO-A1 9721648, 1997. (d) Trost, B. M.; Gerusz, V. J. J. Am. Chem. Soc.
1995, 117, 5156. (e) Yamamoto, Y.; Al-Masum, M.; Asao, N. J. Am. Chem.
Soc. 1994, 116, 6019. (f) Yamamoto, Y.; Al-Masum, M.; Fujiwara, N.;
Asao, N. Tetrahedron Lett. 1995, 36, 2811. (g) Yamamoto, Y.; Al-Masum,
M. Synlett 1995, 969. (h) Yamamoto, Y.; Al-Masum, M.; Takeda, A. Chem.
Commun. 1996, 831. (i) Yamamoto, Y.; Al-Masum, M.; Fujiwara, N. Chem.
Commun. 1996, 381. (j) Besson, L.; Gore, J.; Cazes, B. Tetrahedron Lett.
1995, 36, 3853. (k) Al-Masum, M.; Yamamoto, Y. J. Am. Chem. Soc. 1998,
120, 3809
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Org. Lett., Vol. 10, No. 14, 2008

gold π-allene complex I to initially form the cationic gold
σ-alkenyl complex II that loses a proton to form III (Scheme
2). Protonolysis of the Au-C bond of III then releases the
Table 2. Intermolecular Hydroamination of Allenes with
N-Unsubstituted Carbamates Catalyzed by a Mixture of (2)AuCl
(5 mol %) and AgOTf (5 mol %) in Dioxane at 23 °C for 24 h.
Scheme 2
N-allylic carbamate with regeneration of the cationic Au(I)
catalyst.12 Available evidence regarding the gold(I)-catalyzed
hydrofunctionalization of allenes points to rapid and revers-
ible formation of one or more gold π-allene complex
followed by irreversible C-X bond formation.5,8,13 Therefore,
the regioselectivity of gold(I)-catalyzed intermolecular hy-
droamination and hydroalkoxylation is presumably estab-
lished via kinetic trapping of gold(I) π-allene complexes I
and Ia with carbamate and alcohol, respectively, under
Curtin-Hammett conditions (Scheme 2). However, the
origins of this nucleophile-dependent selectivity remain
unclear.10
In summary, we have developed a gold(I)-catalyzed
protocol for the intermolecular hydroamination of allenes.
The protocol was effective for a number of N-unsubstituted
carbamates and was effective for monosubstituted, 1,1- and
1,3-disubstituted, trisubsituted, and tetrasubstituted allenes.
We are currently working toward the development of
enantioselective intermolecular allene hydroamination pro-
tocols and toward an understanding of the nucleophile-
dependent regioselectivity of gold(I)-catalyzed allene hy-
drofunctionalization.
a Yields refer to isolated material of >95% purity. All N-allylic
carbamates were formed in g98% regio- and diastereoisomeric purity unless
noted otherwise. b Employment of enantiomerically enriched (S)-15 (76%
ee) formed racemic 19 in 78% yield.
Stereochemical analysis of the gold(I)-catalyzed hydro-
functionalization of C-C multiple bonds has consistently
supported outer-sphere pathways for C-X (X ) N, O, C)
bond formation.5,8,11 It therefore appears likely that the
intermolecular hydroamination of allenes catalyzed by (2)AuCl/
AgOTf occurs via outersphere attack of the carbamate on
Acknowledgment is made to the NSF (CHE-0555425),
NIH (GM-080422), and Johnson&Johnson for support of this
research.
Supporting Information Available: Experimental pro-
cedures and scans of NMR spectra for N-allylic carbamates.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(10) It appears unlikely that these regiochemical differences can be
attributed soley to the steric profile of the respective nucleophiles as reaction
of 3 with 2-phenyl-1-ethanol catalyzed by (2)AuCl/AgOTf led to formation
of a 4.4:1 mixture of 3-methyl-1-phenethoxy-2-butene and 1,1-dimethyl-
1-phenethoxy-2-propene: Zhang, Z.; Widenhoefer, R. A. Unpublished
OL8010858
results
.
(11) (a) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem.
Soc. 2004, 126, 4526. (b) Zhang, J.; Yang, C.-G.; He, C. J. Am. Chem.
Soc. 2006, 128, 1798. (c) Hashmi, A. S. K.; Weyrauch, J. P.; Frey, W.;
Bats, J. W. Org. Lett. 2004, 6, 4391. (d) Liu, Y.; Song, F.; Song, Z.; Liu,
(12) Kova´cs, G.; Ujaque, G.; Lledo´s, A. J. Am. Chem. Soc. 2008, 130,
853.
(13) Zhang, Z.; Bender, C. F.; Widenhoefer, R. A. J. Am. Chem. Soc.
M.; Yan, B. Org. Lett. 2005, 7, 5409
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2007, 129, 14148.
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