2-bromonaphthalene proceeded in comparable yield (68%,
entry 12) to the analogous transformation of 2 (73% yield,
entry 1). However, treatment of 1-allyl-1-methyl-3-phenyl-
urea (4) with 2-bromonaphthalene under identical conditions
provided 97% isolated yield of 9 (entry 2).
Substrates bearing N1-methyl and N3-benzyl groups (6,
entry 8) and N1-benzyl and N3-(p-methoxyphenyl) groups
(5, entries 6 and 7) were also transformed to the desired
products in moderate to good yield.16 The efficient reactivity
of the latter substrate (5) is particularly noteworthy, as the
N-benzyl and N-(4-methoxyphenyl) substituents can poten-
tially be cleaved from the product under orthogonal condi-
tions to allow further functionalization.17 Unfortunately, the
method was not effective for transformation of a urea
substrate in which N3 was unprotected.18 In addition,
attempts to cyclize a substrate bearing a N3-(R-methylbenzyl)
group failed to provide the cyclic urea product.
The urea carboamination reactions were found to be
effective with a broad array of aryl bromides, including
substrates bearing functional groups such as nitriles (entry
8), tert-butyl esters (entry 6), trifluoromethyl substituents
(entry 4), nonenolizable ketones (entry 5), and ortho sub-
stituents (entries 7 and 10). Although reactions involving
electron-poor and electron-neutral aryl halides generally
provided good to excellent yields of the substituted imida-
zolidin-2-one products, modest yields were obtained with
the electron-rich 4-bromoanisole (entry 11).
product 24 was obtained as a single diastereomer. The
unreacted Z-isomer was observed by H NMR analysis of
1
the crude reaction mixture, which suggests the E/Z mixture
is effectively resolved to a single product diastereomer
because of the differences in kinetic reactivity between the
two isomers. Crystallographic analysis of 24 indicated that
the reaction had proceeded with syn addition of the arene
and the urea nitrogen across the carbon-carbon double bond.
This syn addition selectivity is analogous to that previously
observed in Pd-catalyzed carboamination reactions of γ-un-
saturated amines.8
The Pd-catalyzed carboamination of cyclopentene deriva-
tive 25 with 4-bromotoluene proceeded under our standard
conditions to afford syn-addition product 26 in excellent yield
(84%) with >20:1 diastereoselectivity (eq 4).19 However,
attempts to effect the cyclization of the cyclohexene-
containing substrate 27 using the Pd/Xantphos catalyst
provided only trace amounts of the desired product. After
some experimentation, a catalyst composed of Pd2(dba)3 and
PEt3 was found to provide the cyclized product 28 in 46%
yield with >20:1 dr (eq 5). Interestingly, the product 28 was
To probe both the scope and the mechanism of these
transformations further, three substrates bearing internal
alkenes and one substrate bearing a 1,1-disubstituted alkene
were prepared and subjected to the carboamination reaction
conditions. The 1,1-disubstituted compound 20 was con-
verted to 21 in 77% yield under our standard reaction
conditions (eq 3).
As shown in eq 4, treatment of butenyl-substituted urea
22 with 23 in the presence of NaOtBu and the Pd2(dba)3/
Xantphos catalyst generated 24 in 50% yield. Interestingly,
although 22 was employed as a 4:1 mixture of E/Z isomers,
determined to be arylated at C-5 rather than at the expected
C-4 position; the addition again occurred with syn stereo-
chemistry.20,21
The stereochemical and regiochemical outcomes of the
transformations of 22, 25, and 27 suggest the mechanism of
the N-allylurea carboaminations is analogous to that previ-
ously described for related transformations of γ-aminoalk-
enes.8,20 As shown in Scheme 1, oxidative addition of the
aryl bromide to Pd(0) would generate 29, which could be
(15) The formation of side products resulting from base-mediated
isomerization of the N-allyl group to a N-1-propenyl group was observed
in reactions of 7. This isomerization also occurred when 7 was heated with
NaOtBu in the absence of Pd.
(16) Substrates 4-7, 20, 22, 25, and 27 were obtained in 79-97% yield
from treatment of the corresponding allylamine with the appropriate
isocyanate as described above.
(17) (a) Suh, M.-J.; Kim, S. W.; Beak, S. I.; Ha, H.-J.; Lee, W. K. Synlett
2004, 489-492. (b) Kise, N.; Kashiwagi, K.; Watanabe, M.; Yoshida, J.-i.
J. Org. Chem. 1996, 61, 428-429. (c) Santos, A. G.; Pereira, J.; Afonso,
C. A. M.; Frenking, G. Chem.-Eur. J. 2005, 11, 330-343.
(18) Attempts to transform substrates bearing unprotected N3 moieties
led to the formation of products resulting from tandem N-arylation and
carboamination in low yield (ca. 30%). For a related reaction of aliphatic
amines, see: Yang, Q.; Ney, J. E.; Wolfe, J. P. Org. Lett. 2005, 7, 2575-
2578.
(19) The connectivity and stereochemistry of 26 and 28 were determined
through 1H NMR COSY and nOe experiments. See the Supporting
Information for complete details of stereochemical assignments.
(20) Related isomers have been observed in Pd/P(t-Bu)2Me-catalyzed
carboaminations of N-(p-methoxyphenyl)-2-(cyclopent-2-enylethyl)amine.
See: Ney, J. E.; Wolfe, J. P. J. Am. Chem. Soc. 2005, 127, 8644-8651.
(21) A small amount of N-(cyclohex-2-enyl)aniline was observed as a
side product in this reaction.
Org. Lett., Vol. 8, No. 12, 2006
2533