Rhodium-catalyzed reductive mannich coupling of vinyl ketones to N-sulfonylimines mediated by hydrogen

Article abstract of DOI:10.1021/jo070779w

(Chemical Equation Presented) Catalytic hydrogenation of methyl vinyl ketone (MVK) and ethyl vinyl ketone (EVK) in the presence of N-(o-nitrophenylsulfonyl)imines 8a-13a at ambient pressure with tri-2-furylphosphine-ligated rhodium catalysts enables forma

Full text of DOI:10.1021/jo070779w

protected aldimines mediated by silane that provides direct
access to the â-lactam.13b In the same year, Matsuda described
a rhodium-catalyzed reductive Mannich coupling of acrylates
to N-tosylaldimines.13c The cobalt- and iridium-catalyzed Man-
nich couplings en route to â-lactams exhibit high levels of syn-
and anti-diastereoselectivity, respectively. Finally, an organo-
catalytic reductive Mannich coupling employing a proline
derived secondary amine catalyst mediated by Hantzsch ester
recently was reported by Cordova.13d
Rhodium-Catalyzed Reductive Mannich Coupling
of Vinyl Ketones to N-Sulfonylimines Mediated
by Hydrogen
Susan A. Garner and Michael J. Krische*
Department of Chemistry and Biochemistry, UniVersity of Texas
at Austin, 1 UniVersity Station A5300, Austin, Texas 78712-1167
Using elemental hydrogen as the terminal reductant, we have
developed a diverse set of catalytic reductive C-C couplings,1g
including hydrogen-mediated aldol couplings of vinyl ketones.3
For such aldol couplings, it was found that high levels of syn-
diastereoselectivity could be achieved through the use of cationic
rhodium catalysts ligated by tri-2-furylphosphine.3e-g These
studies suggest the feasibility of related reductive Mannich
couplings mediated by hydrogen. Here, we report that catalytic
hydrogenation of vinyl ketones in the presence of N-arylaldi-
mines 1a-4a delivers the products of reductive Mannich
coupling in excellent yield. Additionally, we find that N-
sulfonylimines 7a-13a engage reductive Mannich coupling with
high levels of syn-diastereoselectivity in moderate to good yield.
Our initial studies focused on the hydrogenative coupling of
methyl vinyl ketone (MVK) to N-arylaldimines 1a-6a derived
from p-nitrobenzaldehyde (Table 1). It was found that coupling
of MVK to imine 1a derived from aniline gave the desired
reductive Mannich product 1b in excellent yield, though poor
mkrische@mail.utexas.edu
ReceiVed April 18, 2007
Catalytic hydrogenation of methyl vinyl ketone (MVK) and
ethyl vinyl ketone (EVK) in the presence of N-(o-nitrophe-
nylsulfonyl)imines 8a-13a at ambient pressure with tri-2-
furylphosphine-ligated rhodium catalysts enables formation
of Mannich products 8b-13b and 8c-13c with moderate
to good levels of syn-diastereoselectivity. As revealed by an
assay of various N-protecting groups, excellent yields of
reductive Mannich product also are obtained for N-arylimines
1a-4a, although diminished levels of syn-diastereoselectivity
are observed. Coupling of MVK to imine 8a under a
deuterium atmosphere provides deuterio-8b, which incor-
porates a single deuterium atom at the former enone
â-position.
(2) For rhodium-catalyzed reductive aldol reaction mediated by silane,
see: (a) Revis, A.; Hilty, T. K. Tetrahedron Lett. 1987, 28, 4809. (b)
Matsuda, I.; Takahashi, K.; Sato, S. Tetrahedron Lett. 1990, 31, 5331. (c)
Taylor, S. J.; Morken, J. P. J. Am. Chem. Soc. 1999, 121, 12202. (d) Zhao,
C.-X.; Bass, J.; Morken, J. P. Org. Lett. 2001, 3, 2839. (e) Taylor, S. J.;
Duffey, M. O.; Morken, J. P. J. Am. Chem. Soc. 2000, 122, 4528. (f) Fuller,
N. O.; Morken, J. P. Synlett 2005, 1459. (g) Emiabata-Smith, D.; McKillop,
A.; Mills, C.; Motherwell, W. B.; Whitehead, A. J. Synlett 2001, 1302. (h)
Freir´ıa, M.; Whitehead, A. J.; Tocher, D. A.; Motherwell, W. B. Tetrahe-
dron. 2004, 60, 2673. (i) Nishiyama, H.; Shiomi, T.; Tsuchiya, Y.; Matsuda,
I. J. Am. Chem. Soc. 2005, 127, 6972. (j) Ito, J. I.; Shiomi, T.; Nishiyama,
H. AdV. Synth. Catal. 2006, 348, 1235. (k) Shiomi, T.; Ito, J.-I.; Yamamoto,
Y.; Nishiyama, H. Eur. J. Org. Chem. 2006, 5594. (l) Willis, M. C.;
Woodward, R. L. J. Am. Chem. Soc. 2005, 127, 18012.
Following seminal studies by Revis (1987),2a the reductive
aldol reaction has become the topic of intensive investigation.1
To date, catalysts for reductive aldol coupling based on
rhodium,2,3 cobalt,4 iridium,5 ruthenium,6 palladium,7 copper,8,9
nickel,10 and indium11,12 have been devised. Related reductive
Mannich couplings have received far less attention.13 The first
reductive Mannich coupling was reported by Isayama (1992)
and involves the cobalt-catalyzed coupling of ethyl crotonate
to N-methylbenzaldimine mediated by phenylsilane.13a Upon
heating, this Mannich product is converted to the corresponding
â-lactam. In 2002, Morken reported a related iridium-catalyzed
reductive Mannich coupling of trifluorophenyl acrylate to PMP-
(3) For rhodium-catalyzed reductive aldol reaction mediated by hydrogen,
see: (a) Jang, H. Y.; Huddleston, R. R.; Krische, M. J. J. Am. Chem. Soc.
2002, 124, 15156. (b) Huddleston, R. R.; Krische, M. J. Org. Lett. 2003, 5,
1143. (c) Koech, P. K.; Krische, M. J. Org. Lett. 2004, 6, 691. (d) Marriner,
G. A.; Garner, S. A.; Jang, H. Y.; Krische, M. J. J. Org. Chem. 2004, 69,
1380. (e) Jung, C. K.; Garner, S. A.; Krische, M. J. Org. Lett. 2006, 8,
519. (f) Han, S. B.; Krische, M. J. Org. Lett. 2006, 8, 5657. (g) Jung, C.
K.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 17051.
(4) For cobalt-catalyzed reductive aldol reaction, see: (a) Isayama. S.;
Mukaiyama, T. Chem. Lett. 1989, 2005. (b) Baik, T. G.; Luis, A. L.; Wang,
L. C.; Krische, M. J. J. Am. Chem. Soc. 2001, 123, 5112. (c) Wang, L. C.;
Jang, H.-Y.; Roh, Y.; Lynch, V.; Schultz, A. J.; Wang, X.; Krische, M. J.
J. Am. Chem. Soc. 2002, 124, 9448. (d) Lam, H. W.; Joensuu, P. M.; Murray,
G. J.; Fordyce, E. A. F.; Prieto, O.; Luebbers, T. Org. Lett. 2006, 8, 3729.
(5) For iridium-catalyzed reductive aldol reaction, see: (a) Zhao. C. X.;
Duffey, M. O.; Taylor, S. J.; Morken, J. P. Org. Lett. 2001, 3, 1829.
(6) For ruthenium-catalyzed reductive aldol reaction, see: Doi, T.;
Fukuyama, T.; Minamino, S.; Ryu, I. Synlett 2006, 18, 3013.
(1) For reviews encompassing the topic of reductive aldol coupling,
see: (a) Motherwell, W. B. Pure Appl. Chem. 2002, 74, 135. (b) Huddleston,
R. R.; Krische, M. J. Synlett 2003, 12. (c) Jang, H.-Y.; Huddleston, R. R.;
Krische, M. J. Chemtracts 2003, 16, 554. (d) Jang, H.-Y.; Krische, M. J.
Eur. J. Org. Chem. 2004, 19, 3953. (e) Jang, H.-Y.; Krische, M. J. Acc.
Chem. Res. 2004, 37, 653. (f) Chiu, P. Synthesis 2004, 2210. (g) Ngai,
M.-Y.; Kong, J.-R.; Krische, M. J. J. Org. Chem. 2007, 72, 1063. (h) Garner,
S. A.; Krische, M. J. Metal Catalyzed Reductive Aldol Coupling. In Modern
Reductions; Andersson, P., Munslow, I., Eds.; Wiley-VCH: Weinheim,
Germany, 2007, in press.
(7) For palladium-catalyzed reductive aldol reaction, see: (b) Kiyooka,
S. I.; Shimizu, A.; Torii, S. Tetrahedron Lett. 1998, 39, 5237.
(8) For copper-promoted reductive aldol reaction, see: (a) Chiu, P.; Chen,
B.; Cheng, K. F. Tetrahedron Lett. 1998, 39, 9229. (b) Chiu, P. Synthesis
2004, 13, 2210. (c) For copper-promoted reductive intramolecular Henry
reaction, see: Chung, W. K.; Chiu, P. Synlett 2005, 1, 55. (d) For copper-
promoted and -catalyzed reductive cyclizations of R,â-acetylenic ketones
tethered to ketones, see: Chiu, P.; Leung, S. K. Chem. Commun. 2004,
2308.
10.1021/jo070779w CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/21/2007
J. Org. Chem. 2007, 72, 5843-5846
5843

TABLE 1. Hydrogen-Mediated Reductive Mannich Coupling of
TABLE 2. Hydrogen-Mediated Reductive Mannich Coupling of
MVK to N-Arylaldimines 1a-6aa
MVK to N-Arylsulfonylaldimines 7a and 8aa
entry
aldimine
R1
R2
yield (%)
dr
1
2
3
4
5
6
1a
2a
3a
4a
5a
6a
H
H
H
H
MeO
i-Pr
Me
99
91
99
88
38
11
1.5:1
1.2:1
1.2:1
1:1
1.6:1
2:1
MeO
NO2
H
H
Me
entry
aldimine
X
R1
R2
yield (%)
dr
1
2
3
7a
8a
8a
OTf
OTf
BF4
Me
H
H
H
NO2
NO2
70
78
95
20:1
8:1
11:1
a Cited yields are of isolated material and represent the average of
two runs. See the Supporting Information for detailed experimental
procedures.
a Cited yields are of isolated material and represent the average of two
runs. See the Supporting Information for detailed experimental procedures.
b Coupling to aldimine 2a was conducted with 3 equiv of MVK in the
absence of Li2CO3.
N-arylsulfonylimines, which are configurationally more stable,
were examined as substrates. Gratifyingly, exposure of N-(p-
toluenesulfonyl)imine 7a to conditions for hydrogenative cou-
pling using MVK as the nucleophilic partner provides the
desired Mannich adduct 7b in 70% yield with a 20:1 diaster-
eomeric ratio favoring formation of the syn-diastereomer (Table
2, entry 1). The stereochemistry of 7b was corroborated by
single-crystal X-ray diffraction analysis of a diastereomerically
pure sample. Given the relatively facile cleavage of N-
(nitrobenzenesulfonamides),15 the hydrogenative coupling of
MVK to the N-(nitrobenzenesulfonyl)imine 8a was explored.
The desired Mannich adduct 8b was produced in 78% yield
with an 8:1 diastereomeric ratio, again favoring formation of
the syn-diastereomer (Table 2, entry 2). Finally, using Rh-
(COD)2BF4 as the catalyst precursor, a 95% yield of the desired
Mannich adduct 8b was obtained with a diastereomeric ratio
of 11:1 (Table 2, entry 3).
levels of syn-diastereoselection were observed (Table 1, entry
1). In an effort to improve diastereoselectivity, variation of the
electronic features of the N-aryl residue was explored. However,
while aldimines 2a and 3a, derived from p-anisidine and
p-nitroaniline, respectively, provide the reductive Mannich
products 2b and 3b in excellent yield, the observed levels of
syn-diastereoselection remained unsatisfactory (Table 1, entries
2 and 3). Finally, it was reasoned that aldimines incorporating
sterically more demanding N-aryl residues might couple with
greater levels of diastereoselection. Accordingly, aldimines 4a,
5a, and 6a were examined, which incorporate o-methoxyphenyl,
o-isopropylphenyl, and o,o-dimethylphenyl N-aryl residues.
Unfortunately, heightened levels of diastereoselection were not
observed in couplings of MVK to 4a-6a, and the increased
steric demand of substrates 5a and 6a adversely affected
conversion and, hence, isolated chemical yield (Table 1, entries
4-6).
These optimized conditions were assayed against a diverse
set of N-(nitrobenzenesulfonyl)imines. It was found that the
hydrogenative Mannich coupling proceeds most efficiently for
highly electrophilic N-(o-nitrobenzenesulfonyl)imines, even then
requiring catalyst loadings of 10 mol % in most cases to enforce
good conversion. Due to extended reaction times (24 h), Na2-
SO4 was required to suppress imine hydrolysis and the formation
of hydroxy-bridged dimers of rhodium. Ultimately, using
commercially available MVK and EVK as pronucleophiles,
N-(nitrobenzenesulfonyl)imines 8a-13a were converted to the
Mannich adducts 8b-13b and 8c-13c, respectively (Table 3).
To gain further insight into the reaction mechanism, the
reductive coupling of MVK and p-nitrobenzaldimine 8a was
performed with elemental deuterium. The Mannich coupling
product deuterio-8b incorporates a single deuterium atom at the
former enone â-position. Deuterium incorporation at the R-car-
bon of the product is not observed, thus excluding Morita-
Baylis-Hillman pathways en route to product. The strict
incorporation of a single deuterium atom is consistent with a
mechanism involving irreversible enolization via enone hydro-
metallation or enone-imine oxidative coupling to furnish an aza-
rhodacyclopentane, which then hydrogenolytically cleaves to
deliver product (Scheme 1).
The relatively poor levels of diastereoselection in additions
to the N-arylaldimines is potentially due to facile geometrical
isomerism in the presence of the metal catalyst.14 Accordingly,
(9) For copper-catalyzed reductive aldol reaction, see: (a) Ooi, T.; Doda,
K.; Sakai, D.; Maruoka, K. Tetrahedron Lett. 1999, 40, 2133. (b) Lam, H.
W.; Joensuu, P. M. A. Org. Lett. 2005, 7, 4225. (c) Lam, H. W.; Murray,
G. J.; Firth, J. D. Org. Lett. 2005, 7, 5743. (d) Deschamp, J.; Chuzel, O.;
Hannedouche, J.; Riant, O. Angew. Chem., Int. Ed. 2006, 45, 1292. (e)
Chuzel, O.; Deschamp, J.; Chauster, C.; Riant, O. Org. Lett. 2006, 8, 5943.
(f) Zhao, D.; Oisaki, K.; Kanai, M.; Shibasaki, M. Tetrahedron Lett. 2006,
47, 1403. (g) Zhao, D.; Oisaki, K.; Kanai, M.; Shibasaki, M. J. Am. Chem.
Soc. 2006, 128, 14440. (h) Welle, A.; Diez-Gonzalez, S.; Tinant, B.; Nolan,
S. P.; Riant, O. Org. Lett. 2006, 8, 6059.
(10) For nickel-catalyzed reductive aldol reaction, see: Chrovian, C. C.;
Montgomery, J. Org. Lett. 2007, 9, 537.
(11) For a reductive aldol coupling employing stoichiometric quantities
of indium reagent, see: Inoue, K.; Ishida, T.; Shibata, I.; Baba, A. AdV.
Synth. Catal. 2002, 344, 283.
(12) For indium-catalyzed reductive aldol reaction, see: (a) Shibata, I.;
Kato, H.; Ishida, T.; Yasuda, M.; Baba, A. Angew. Chem., Int. Ed. 2004,
43, 711. (b) Miura, K.; Yamada, Y.; Tomita, M.; Hosomi, A. Synlett 2004,
1985.
(13) (a) Isayama, S. Yuki Gosei Kagaku Kyokaishi 1992, 50, 190. (b)
Townes, J.; Evans, M.; Queffelec, J.; Taylor, S. J.; Morken, J. P. Org. Lett.
2002, 4, 2537. (c) Moraoka, T.; Kamiya, S.; Matsuda, I.; Itoh, K. Chem.
Commun. 2002, 1284. (d) Zhao, G.-L.; Cordova, A. Tetrahedron Lett. 2006,
47, 7417.
(14) (a) Eaton, D. R.; Tong, J. P. K. Inorg. Chem. 1980, 19, 740. (b)
Lehn, J.-M. Chem. Eur. J. 2006, 12, 5910 and references cited therein.
(15) For a review on the use of the nitrobenzenesulfonamides in organic
synthesis, see: Kan, T.; Fukuyama, T. Chem. Commun. 2004, 353.
5844 J. Org. Chem., Vol. 72, No. 15, 2007

TABLE 3. Diastereoselective Hydrogen-Mediated Reductive Mannich Coupling of MVK and EVK to N-(o-Nitrophenyl)sulfonylaldimines
8a-13aa-h
a Representative procedure: To a 13 mm × 100 mm test tube charged with Na2SO4 (0.78 mmol, 200 mol %), Fur3P (0.094 mmol, 24 mol %), Rh(COD)2OTf
(0.039 mmol, 10 mol %), and imine (0.39 mmol, 100 mol %) was added dichloromethane (0.2 M). The test tube was sealed, and the reaction mixture was
sparged with Ar(g) followed by H2(g) for 20 s each. The reaction was placed under 1 atm of hydrogen using a balloon, and MVK (1.17 mmol, 300 mol %)
was added to the reaction mixture and it was stirred for 24 h at 35 °C. The reaction mixture was evaporated onto silica, and the product was isolated by flash
chromatography (SiO2: EtOAc/hexane). b For 8b the reaction was conducted with 5 mol % loadings of Rh(COD)2OTf and 12 mol % loadings of Fur3P in
the absence of Na2SO4. c For 9b, 10b, and 11b the reaction was conducted with 500 mol % MVK at 0.4 M dichloromethane. d Couplings to form adducts
8c-13c employ 500 mol % loadings of EVK. e For 8c the reaction was conducted with 5 mol % loadings of Rh(COD)2OTf and 12 mol % loadings of Fur3P.
f For 9c, 10c, and 11c the reaction was conducted at 0.4 M concentration in dichloromethane. g The cited yields are of isolated material and represent the
1
average of two runs. h Diastereomeric ratios were established through H NMR analysis of crude reaction mixtures.
SCHEME 1. Reductive Mannich Coupling under a
Deuterium Atmosphere
added tetraethylorthosilicate (113 mol %). The round-bottomed flask
was equipped with a still head and heated to 160 °C under an
atmosphere of argon. The reaction was allowed to stir for ∼6 h
during which time ethanol was collected in a receiving flask. The
reaction was cooled to room temperature and then ethyl ether was
added to the reaction mixture. The reaction mixture was stirred for
several hours and was then filtered with the aid of cold ethyl ether.
The crude imine was then crystallized from an appropriate solvent.
8a: 1H NMR (400 MHz, CDCl3) δ 7.84-7.89 (m, 3H), 8.20 (d,
J ) 9.9 Hz, 2H), 8.37 (d, J ) 8.9 Hz, 2H), 8.43 (m, 1H), 9.18 (s,
1H); 13C NMR (75 MHz, CDCl3) δ 124.3, 125.0, 131.0, 132.3,
132.9, 135.2, 137.0, 148.6, 151.5, 171.2; HRMS calcd [M + 1]
for C13H10N3O6S 336.0290, found 336.0296; FTIR (film) 1594,
1347, 1165, 1125, 1056, 839, 798, 748, 675, 590 cm-1; mp 186-
187 °C.
General Procedure for Intermolecular Hydrogen-Mediated
Reductive Coupling of Methyl Vinyl Ketone and N-Nosylaldi-
mines. To a 13 mm × 100 mm test tube charged with Na2SO4
(0.78 mmol, 200 mol %), Fur3P (0.094 mmol, 24 mol %), Rh-
(COD)2OTf (0.039 mmol, 10 mol %), and imine (0.39 mmol, 100
mol %) was added dichloromethane (0.2 M). The test tube was
sealed and the reaction system was purged with argon and then
with hydrogen for 20 s each. The reaction was placed under 1 atm
of hydrogen using a balloon, and MVK (1.17 mmol, 300 mol %)
was added to the reaction mixture. The reaction mixture was
allowed to stir for 24 h, at which point the reaction mixture was
In summary, catalytic hydrogenation of methyl vinyl ketone
(MVK) and ethyl vinyl ketone (EVK) in the presence of
N-(nitrophenylsulfonyl)imines 8a-14a at ambient pressure with
tri-2-furylphosphine ligated rhodium catalysts enables formation
of Mannich products 8b-14b and 8c-14c, respectively, with
moderate to good levels of syn-diastereoselectivity. Future
studies will focus on the development of improved second
generation catalysts for hydrogen-mediated reductive Mannich
coupling, enantioselective variants of the transformations re-
ported herein, and the discovery of related C-C bond-forming
hydrogenations.
Experimental Section
General Procedure for the Synthesis of N-Nosylaldimines.
N-Nosylaldimines were prepared according to the procedure esta-
blished by Love.16 To a round-bottomed flask charged with aldehyde
(100 mol %) and 2-nitrobenzenesulfonamide (100 mol %) was
(16) Love, B. E.; Raje, P. S.; Williams, T. C. Synlett. 1994, 493.
J. Org. Chem, Vol. 72, No. 15, 2007 5845

evaporated onto silica gel and the products were separated by
column chromatography (SiO2: EtOAc/hexane). For entry 8b the
reaction was conducted with 5 mol % loadings of Rh(COD)2OTf
and 12 mol % loadings of Fur3P without Na2SO4. For entries 9b,
10b, and 11b the reaction was conducted with 500 mol % MVK at
0.4 M DCM.
reaction was conducted at 5 mol % loadings of Rh(COD)2OTf and
12 mol % loadings of Fur3P. For entries 9c, 10c, and 11c the
reaction was conducted with 500 mol % MVK at 0.4 M DCM.
8c: 1H NMR (400 MHz, d6-acetone) δ 0.70 (t, J ) 7.1 Hz, 3H),
1.23 (d, J ) 6.8 Hz, 3H), 1.96-2.09 (m, 1H), 2.42-2.52 (m, 1H),
3.36-3.44 (m, 1H), 4.84 (d, J ) 9.8 Hz, 1H), 7.46 (br s, 1H), 7.55
(d, J ) 8.8 Hz, 2H), 7.64 (t, J ) 7.6 Hz, 1H), 7.72 (t, J ) 7.6 Hz,
1H), 7.78 (dd, dd, J ) 6.7, 1.4 Hz, 1H), 7.90 (dd, J ) 6.5, 1.4 Hz,
1H), 7.98 (d, J ) 8.8 Hz, 2H); 13C NMR (75 MHz, d6-acetone) δ
6.5, 14.0, 35.4, 51.0, 60.0, 123.0, 124.6, 128.7, 130.5, 132.4, 133.4,
133.8, 147.0, 147.1, 147.3, 211.1; HRMS calcd [M + 1] for
C18H20N3O7S 422.1022, found 422.1026; FTIR (film) 3324, 3099,
8b: 1H NMR (400 MHz, d6-acetone) δ 1.23 (d, J ) 7.0 Hz,
3H), 1.93 (s, 3H), 3.29-3.44 (m, 1H), 4.86 (d, J ) 9.2 Hz, 1H),
7.43 (br s, 1H), 7.56 (d, J ) 8.8 Hz, 2H), 7.63 (t, J ) 7.9 Hz, 1H),
7.72 (t, J ) 6.9 Hz, 1H), 7.77 (m, 1H), 7.88 (dd, J ) 6.5, 1.4 Hz,
1H), 7.96 (d, J ) 8.8 Hz, 2H); 13C NMR (75 MHz, d6-acetone) δ
14.5, 52.6, 60.5, 123.9, 125.5, 129.7,131.3, 133.3, 134.3, 134.7,
147.9, 209.3; HRMS calcd [M + 1] for C17H18N3O7S 408.0865,-
found 408.0866; FTIR (film) 3324, 3099, 2938, 1712, 1607, 1540,
1441, 1349, 1268, 1167, 1124, 1060, 854, 741, 593 cm-1; mp 123-
125 °C.
2978, 1711, 1606, 1540, 1500, 1443, 1349, 1169, 854, 593 cm-1
;
mp 141-142 °C.
Acknowledgment is made to the Robert A. Welch Founda-
tion, Johnson & Johnson, and the NIH-NIGMS (RO1-
GM69445) for partial support of this research. Dr. Oliver Briel
of Umicore of is thanked the generous donation of Rh-
(COD)2BF4.
General Procedure for Intermolecular Hydrogen-Mediated
Reductive Coupling of Ethyl Vinyl Ketone and N-Nosylaldi-
mines. To a 13 mm × 100 mm test tube charged with Na2SO4
(0.78 mmol, 200 mol %), Fur3P (0.094 mmol, 24 mol %), Rh-
(COD)2OTf (0.039 mmol, 10 mol %), and imine (0.39 mmol, 100
mol %) was added dichloromethane (0.2 M). The test tube was
sealed and the reaction system was purged with argon and then
with hydrogen for 20 s each. The reaction was placed under 1 atm
of hydrogen using a balloon, and EVK (1.95 mmol, 500 mol %)
was added to the reaction mixture. The reaction mixture was
allowed to stir for 48 h, at which point the reaction mixture was
evaporated onto silica gel and the products were separated by
column chromatography (SiO2: EtOAc/hexane). For entry 8c the
Supporting Information Available: Experimental details and
spectral data for all new compounds (1H NMR, 13C NMR, IR,
HRMS) and single-crystal X-ray diffraction data corresponding to
compound 7b. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO070779W
5846 J. Org. Chem., Vol. 72, No. 15, 2007