Gold(l)-Catalyzed amination of allylic alcohols with cyclic ureas and related nucleophiles

Article abstract of DOI:10.1021/ol902923e

"Chemical Equation Presented" A 1:1 mixture of [P(t-Bu) ₂-obiphenyl]AuCl and AgSbF₆ catalyzes the intermolecular amination of allylic alcohols with 1-methylimldazolidin-2one and related nucleophiles that, In the case of γ-unsubstituted or γ-methyl- substituted allylic alcohols, occurs with high γ-regioselectivity and syn-stereoselectivlty.

Full text of DOI:10.1021/ol902923e

ORGANIC
LETTERS
2010
Vol. 12, No. 6
1184-1187
Gold(I)-Catalyzed Amination of Allylic
Alcohols with Cyclic Ureas and Related
Nucleophiles
Paramita Mukherjee and Ross A. Widenhoefer*
Duke UniVersity, Department of Chemistry, French Family Science Center,
Durham, North Carolina 27708-0346
rwidenho@chem.duke.edu
Received December 19, 2009
ABSTRACT
A 1:1 mixture of [P(t-Bu)2-o-biphenyl]AuCl and AgSbF6 catalyzes the intermolecular amination of allylic alcohols with 1-methylimidazolidin-2-
one and related nucleophiles that, in the case of γ-unsubstituted or γ-methyl-substituted allylic alcohols, occurs with high γ-regioselectivity
and syn-stereoselectivity.
There has been an ongoing interest in the direct catalytic
amination of underivatized allylic alcohols as a route to
allylic amines and related derivatives.1 Initial headway in
this area was realized through the in situ activation of the
hydroxyl functionality with Lewis acid cocatalysts.2 In 2002,
Ozawa reported the amination of allylic alcohols with anilines
catalyzed by a cationic Pd(II) π-allyl complex in the absence
of a Lewis acidic cocatalyst.3 Since this time, a number of
metals including Pd(0),4 Pt(II),5 Mo(VI),6 Bi(III),7 Au(I), and
Au(III)8 have been shown to catalyze the intermolecular
amination of underivatized allylic alcohols without the
(3) Ozawa, F.; Okamoto, H.; Kawagishi, S.; Yamamoto, S.; Minami,
T.; Yoshifuji, M. J. Am. Chem. Soc. 2002, 124, 10968.
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Ishiyama, T.; Yamamoto, S.; Kawagishi, S.; Murakami, H.; Yoshifuji, M.
Organometallics 2004, 23, 1698. (d) Kayaki, Y.; Koda, T.; Ikariya, T. J.
Org. Chem. 2004, 69, 2595. (e) Piechaczyk, O.; Doux, M.; Ricard, L.; le
Floch, P. Organometallics 2005, 24, 1204. (f) Thoumazet, C.; Gru¨tzmacher,
H.; Deschamps, B.; Ricard, L.; le Floch, P. Eur. J. Inorg. Chem. 2006,
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Chem. Soc. 2006, 128, 14306. (h) Mora, G.; Deschamps, B.; van Zutphen,
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Utsunomiya, M.; Miyamoto, Y.; Ipposhi, J.; Ohshima, T.; Mashima, K.
Org. Lett. 2007, 9, 3371. (c) Mora, G.; Piechaczyk, O.; Houdard, R.;
Mezailles, N.; Le Goff, X. F.; le Floch, P. Chem.sEur. J. 2008, 14, 10047.
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10.1021/ol902923e  2010 American Chemical Society
Published on Web 02/24/2010

assistance of a Lewis acidic cocatalyst.9 Although a number
of these transformations display high regio- and/or stereo-
selectivity, regiospecific amination of allylic alcohols remains
problematic, presumably due to the intermediacy of π-allyl
complexes or allylic carbocations. Here we describe a
gold(I)-catalyzed protocol for the intermolecular amination
of allyl alcohols with 1-methylimidazolidin-2-one (1) and
related nucleophiles that, in the case of γ-unsubstituted or
γ-methyl-substituted allylic alcohols, occurs with high γ-re-
gioselectivity and syn-stereoselectivity.10
Table 1. Amination of Allyl Alcohol (2 equiv) as a Function of
Nucleophile Catalyzed by a Mixture of (2)AuCl (5 mol %) and
AgSbF6 (5 mol %) in Dioxane
We recently reported the intermolecular hydroamination
of unactivated 1-alkenes with cyclic ureas catalyzed by
gold(I) o-biphenylphosphine complexes.11 As part of our
ongoing efforts to expand the scope of intermolecular alkene
hydroamination, we investigated the gold(I)-catalyzed reac-
tion of cyclic ureas with allylic ethers. However, reaction
of 1 with either allyloxytrimethylsilane or diallyl ether
catalyzed by a 1:1 mixture of (2)AuCl [2 ) P(t-Bu)2-o-
biphenyl] and AgSbF6 gave none of the anticipated hy-
droamination products but instead led to allylic amination
with isolation of 1-allyl-3-methylimidazolidin-2-one (3) in
>95% yield (Scheme 1).
a Isolated material of >95% purity. b One equivalent of allyl alcohol
employed. c N,N-Diallyl-4-methoxybenzenesulfonamide was also isolated
in 20% yield.
allylation with allylic alcohol, albeit with diminished ef-
ficiency (Table 1, entries 3 and 8).
Scheme 1
We evaluated the scope and stereospecificity of the gold(I)-
catalyzed allylation of 1 as a function of allylic alcohol (Table
2). In the cases of γ-unsubstituted or γ-methyl-substituted
allylic alcohols, amination occurred selectively at the γ-car-
bon atom of the allylic alcohol. For example, gold(I)-
catalyzed reaction of 1 with 1,1-dideuterio-2-propenol led
to exclusive formation of 1-(3,3-dideuterio-2-propenyl)-3-
methylimidazolidin-2-one (3-γ,γ-d2) (Table 2, entry 1).
Likewise, gold(I)-catalyzed amination of 3-buten-2-ol with
1 led to exclusive formation of the N-2-butenylurea 4, while
amination of 2-buten-1-ol with 1 formed exclusively the
N-(1-methyl-2-propenyl)urea 8 (Table 2, entries 2 and 6).
Gold(I)-catalyzed reaction of 1 with 2-deuterio-3-penten-2-
ol (10-1-d1) formed allylic urea 11-γ-d1 as the exclusive
product (Table 2, entry 8), while gold(I)-catalyzed reaction
of 1 with 4-hexen-3-ol (13) led to exclusive formation of
urea 14 (Table 2, entry 10). Conversely, gold(I)-catalyzed
amination of cinnamyl alcohol with 1 led to exclusive
formation of R-substitution product 5, whereas gold(I)-
catalyzed amination of 3-methyl-2-buten-1-ol with 1 led to
formation of a 12:1 mixture of R-substitution product 6a and
γ-substitution product 6b in quantitative yield (Table 2,
entries 11 and 12).
The efficient amination of both allyloxytrimethylsilane and
diallyl ether suggested that unprotected allylic alcohols might
also undergo gold(I)-catalyzed allylic amination. Indeed,
reaction of 1 with allyl alcohol (1 equiv) catalyzed by
(2)AuCl/AgSbF6 at 60 °C for 2 h led to isolation of 3 in
99% yield (Table 1, entry 1).12 In addition to 1, oxazolidin-
2-one, imidazolidin-2-one, and primary and secondary sul-
fonamides underwent efficient gold(I)-catalyzed allylation
with allylic alcohol (Table 1, entries 2 and 4-7). Pyrrolidin-
2-one and benzyl carbamate also underwent gold(I)-catalyzed
(9) See also: Defieber, C.; Ariger, M. A.; Moriel, P.; Carreira, E. M.
Angew. Chem., Int. Ed. 2007, 46, 3139.
(10) For relevant examples of the gold-catalyzed addition of nucleophiles
to allylic alcohols and related substrates see: (a) Bandini, M.; Eichholzer,
A. Angew. Chem., Int. Ed. 2009, 48, 9533. (b) Aponick, A.; Li, C.-Y.;
Biannic, B. Org. Lett. 2008, 10, 669. (c) Aponick, A.; Li, C.-Y.; Palmes,
J. A. Org. Lett. 2009, 11, 121. (d) Aponick, A.; Li, C.-Y.; Malinge, J.;
Marques, E. F. Org. Lett. 2009, 11, 4624. (e) Lu, Y.; Fu, X.; Chen, H.; Du,
X.; Jia, X.; Liu, Y. AdV. Synth. Catal. 2009, 351, 129. (f) Shu, X.-Z.; Liu,
X.-Y.; Xiao, H.-Q.; Ji, K.-Q.; Guo, L.-N.; Liang, Y.-M. AdV. Synth. Catal.
2008, 350, 243. (g) Terrasson, V.; Marque, S.; Georgy, M.; Campagne,
J.-M.; Prim, D. AdV. Synth. Catal. 2006, 348, 2063. (h) Georgy, M.;
Boucard, V.; Debleds, O.; Dal Zotto, C.; Campagne, J.-M. Tetrahedron
2009, 65, 1758. (i) Kothandaraman, P.; Foo, S. J.; Chan, P. W. H. J. Org.
Chem. 2009, 74, 5947.
The presence of a γ-selective pathway in the gold(I)-
catalyzed amination of γ-methyl-substituted allylic alcohols
(12) Mixtures of (2)AuCl and AgOTf also catalyzed the conversion of
1 and allyl alcohol to 3 at 60 °C. Conversely, control experiments ruled
out the contribution of acid- or silver-catalyzed pathways to the amination
of allyl alcohol. Heating a mixture of 1 and allyl alcohol with a catalytic
amount of (1) (2)AuCl, (2) AgSbF6, (3) a 1:1 mixture of AgSbF6 and 2, (4)
HOTf, or (5) a 1:1 mixture of HOTf and 2 in 1,4-dioxane (0.5 mL)
at 100 °C for 24 h led to no detectable consumption of 1 or formation
of 3.
(11) Zhang, Z.; Lee, S. D.; Widenhoefer, R. A. J. Am. Chem. Soc. 2009,
131, 5372.
Org. Lett., Vol. 12, No. 6, 2010
1185

Scheme 2
Table 2. Allylation of 1-Methylimidazolidin-2-one (1) as a
Function of Allylic Alcohol Catalyzed by a Mixture of (2)AuCl
(5 mol %) and AgSbF6 (5 mol %) in Dioxane (Nuc )
N-Methylimidazolidin-2-one)
σ-activation of the hydroxyl group appears to be at odds with
the low oxophilicity of gold(I), particularly considering the
modest nucleophilicity of 1. Rather, a mechanism involving
π-activation of the allylic CdC bond also accounts for the
stereochemistry of gold(I)-catalyzed allylic amination and
appears to be more in line with the pronounced π-acidity of
cationic gold(I) complexes.14 Notably, Maseras has proposed
a π-activation pathway for the gold(I)-catalyzed isomeriza-
tion of allylic ethers with alcohols on the basis of DFT
calculations.15 Guided by these results, we propose a
mechanism for gold(I)-catalyzed allylic amination of (R)-
10 initiated by formation of the gold(I) π-alkene complexes
si-I and re-I (Scheme 3). Outersphere addition of 1 to si-I
and re-I, facilitated by an N-H···O hydrogen bond (si-II
and re-II),15 would form the cyclic, hydrogen-bonded gold
alkyl intermediates (S,S,R)-III and (R,R,R)-III, respectively
(Scheme 3). Anti-elimination of a hydrogen-bonded water
molecule followed by displacement of gold would then
release allylic ureas (S,E)-11 and (R,Z)-11 (Scheme 3).
Preferential formation of (S,E)-11 relative to (R,Z)-11
presumably results from the unfavorable cis relationship of
the gold moiety and the C1 methyl group in the transition
state for formation of (R,R,R)-III that is absent in the
transition state for formation of (S,S,R)-III.
The π-activation mechanism for allylic amination outlined
in Scheme 3 does not, however, account for the formation
of R-substitution products, as was observed for the amination
of cinnamyl alcohol and 3-methyl-2-buten-1-ol (Table 2,
entries 11 and 12). These R-substitution products may result
from the presence of a Lewis acid-catalyzed reaction pathway
involving carbocationic intermediates. Alternatively, we have
obtained evidence for the formation of R-substitution product
6a in the gold(I)-catalyzed amination of 3-methyl-2-buten-
1-ol with 1 through indirect pathways, in particular, the
isomerization of γ-addition product 6b under reaction
a Conditions: A ) 2 equiv of alcohol, 60 °C, 24 h; B ) 1 equiv of
alcohol, 60 °C, 24 h; C ) 2 equiv of alcohol, 25 °C, 36 h; D ) 2 equiv of
alcohol, 100 °C, 48 h. b Isolated material of >95% purity. c Determined by
1H NMR analysis of the purified reaction mixture.
pointed to the potential for 1,3-chirality transfer in these
transformations. Indeed, two experiments employing enan-
tiomerically enriched allylic alcohols established the pref-
erential addition of urea to the alkene π-face syn to the
departing hydroxyl group. In one experiment, gold(I)-
catalyzed reaction of (R)-10 (92% ee) with 1 at 60 °C gave
a 4.2:1 mixture of (S,E)-11 with 86% ee and (R,Z)-11 with
92% ee in 99% combined yield (Scheme 2). In a second
experiment, gold(I)-catalyzed reaction of 1 with (R)-13 (96%
ee) at 60 °C for 24 h led to isolation of a 4.3:1 mixture of
(S,E)-14 with 91% ee and (R,Z)-14 with g95% ee in
quantitative yield (Scheme 2).
(13) (a) Magid, R. M. Tetrahedron 1980, 36, 1901. (b) Paquette, L. A.;
Stirling, C. J. M. Tetrahedron 1992, 48, 7383.
(14) For examples of cationic, two-coordinate gold(I) π-alkene com-
plexes see: (a) Brown, T. J.; Dickens, M. G.; Widenhoefer, R. A. J. Am.
Chem. Soc. 2009, 131, 6350. (b) Brown, T. J.; Dickens, M. G.; Widenhoefer,
R. A. Chem. Commun. 2009, 6451. (c) Hooper, T. N.; Green, M.; Mcgrady,
J. E.; Patel, J. R.; Russell, C. A. Chem. Commun. 2009, 3877. (d) Zuccaccia,
D.; Belpassi, L.; Tarantelli, F.; Macchioni, A. J. Am. Chem. Soc. 2009,
131, 3170. (e) de Fre´mont, P.; Marion, N.; Nolan, S. P. J. Organomet.
Chem. 2009, 694, 551. (f) Shapiro, N. D.; Toste, F. D. Proc. Natl. Acad.
Sci. U.S.A. 2008, 105, 2779.
The stereochemical outcome of the gold(I)-catalyzed
amination of (R)-10 and (R)-13 with 1 is characteristic of a
concerted SN2′ substitution.13 However, a mechanism for the
gold(I)-catalyzed γ-amination of allylic alcohols involving
(15) Paton, R. S.; Maseras, F. Org. Lett. 2009, 11, 2237.
1186
Org. Lett., Vol. 12, No. 6, 2010

transposition of 3-methyl-2-buten-1-ol was validated through
a second set of experiments. When an equimolar mixture of
3-methyl-2-buten-1-ol and 1 that contained a catalytic amount
of (2)AuCl and AbSbF6 was heated at 60 °C in dioxane-d8,
1H NMR analysis at low conversion (∼17%) revealed the
presence of 2-methyl-3-buten-2-ol and γ-alkoxylation prod-
uct 15 that together accounted for ∼3% of the reaction
mixture (Scheme 5). These compounds persisted throughout
the conversion of 3-methyl-2-buten-1-ol to 6a and 6b and
were consumed at high conversion (∼95%). Importantly,
gold(I)-catalyzed reaction of 1 with either 2-methyl-3-buten-
2-ol or 15 formed 6a as the exclusive product at rates that
were g6 times greater than the rate of reaction of 1 with
3-methyl-2-buten-1-ol under comparable conditions.17
Scheme 3
Scheme 5
conditions and the allylic transposition of 3-methyl-2-buten-
1-ol followed by γ-addition of 1. In support of the former
pathway, an equimolar mixture of 1, 6b, cinnamyl alcohol,
and water that contained a catalytic amount of (2)AuCl and
AbSbF6 was heated at 60 °C in dioxane for 24 h.16 1H NMR
analysis of the purified reaction mixture revealed a ∼2:1:1
mixture of unreacted 6b, cinnamyl urea 5, and isomerized
urea 6a (Scheme 4).
In summary, we have developed a gold(I)-catalyzed
method for the amination of allyl alcohols with 1-methylimi-
dazolidin-2-one (1) and related nucleophiles that proceeds
in high yields under mild conditions. In the case of
γ-unsubstituted or γ-methyl-substituted allylic alcohols,
amination occurs with high γ-regioselectivity and syn-
stereoselectivity. In the case of 3-methyl-2-buten-1-ol or
cinnamyl alcohol, gold(I)-catalyzed amination led to pre-
dominant formation of R-amination products via secondary
π-activation reaction pathways or through a Lewis acid
catalysis involving carbocationic intermediates. We are
currently working toward expanding the scope of gold(I)-
catalyzed allylic amination with respect to nucleophile and
toward the development of more general and more selective
catalyst systems for the γ-amination of underivatized allylic
alcohols.
Scheme 4
Acknowledgment is made to the NIH (GM-080422) for
support of this research.
Supporting Information Available: Experimental pro-
cedures, analytical and spectroscopic data, and copies of
HPLC traces and NMR spectra for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
A pathway for formation of 6a in the gold(I)-catalyzed
amination of 3-methyl-2-buten-1-ol initiated by allylic
(16) These conditions mimic the reaction mixture at ∼50% conver-
sion.
(17) See the Supporting Information for details regarding these experi-
ments.
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