Reductive one-carbon homologation of aldehydes and ketones

Article abstract of DOI:10.1021/jo0516741

A rhodium-catalyzed methylenation-hydrogenation cascade process allows the homologation of carbonyl compounds to lead to the corresponding alkanes in high yields.

Full text of DOI:10.1021/jo0516741

Reductive One-Carbon Homologation of
Aldehydes and Ketones
H e´ l e` ne Lebel* and Chehla Ladjel
We have shown that multicatalytic processes including
our rhodium-catalyzed methylenation reaction allowed
the formation of various substituted alkenes directly from
D e´ partement de chimie, Universit e´ de Montr e´ al,
P.O. Box 6128, Station Downtown, Montr e´ al, Qu e´ bec,
Canada H3C 3J7
5
alcohols, without isolation of any intermediate. We can
take also advantage of the dual catalytic activity of the
Wilkinson complex toward carbonyl and alkene deriva-
tives to functionalize in situ our methylene unit. Indeed,
we have recently disclosed a new rhodium-catalyzed
cascade process involving a methylenation-hydrobora-
tion reaction sequence to produce the corresponding
helene.lebel@umontreal.ca
Received August 9, 2005
6
organoborane, which was then oxidized or homologated.
In this paper, we present a similar rhodium-catalyzed
process in which a hydrogenation reaction is performed
in cascade with a methylenation reaction to produce
7
directly alkanes from carbonyl compounds.
A rhodium-catalyzed methylenation-hydrogenation cascade
process allows the homologation of carbonyl compounds to
lead to the corresponding alkanes in high yields.
8
Wilkinson’s complex, ClRh(PPh
3
)
3
is well-known to
catalyze a variety of reactions with alkenes, including
hydrogenation. It was anticipated that we could switch
9,10
the atmosphere of argon to hydrogen after the methyl-
enation is completed to directly produce the correspond-
ing alkane. Indeed, it was possible to react in situ with
hydrogen the alkene produced by the methylenation of
Cascade processes are a very efficient way to produce
a variety of compounds while minimizing the number of
manipulations, reagents, and solvents, thus decreasing
the amount of generated waste and improving the overall
(
S)-2-(t-Boc-amino)-3-phenylpropan-1-al and obtain the
corresponding alkane 1 in 77% isolated yield (eq 2).
1
efficiency. As a number of transition-metal complexes
are known to catalyze more than one chemical transfor-
mation, they are very well suited to be included in
cascade processes. Furthermore, it is also possible to
combine more than one transition-metal complex that
catalyzed different chemical transformations in multi-
2
catalytic processes. We have recently reported the me-
thylenation of a variety of carbonyl derivatives catalyzed
by Wilkinson’s complex in the presence of trimethylsi-
lyldiazomethane, triphenylphosphine, and 2-propanol,
producing the corresponding terminal alkene in high
However, the basic nitrogen functionality present in
the substrate in eq 2 apparently made the resulting
methylenation product particularly suitable for hydro-
genation, since when this functionality is absent, further
conversion to an alkane such as 2 is not observed (Table
3
,4
yields (eq 1).
1
, entry 1). We postulated that the catalytic activity of
(
1) (a) Catellani, M. Synlett 2003, 298-313. (b) McCarroll, A. J.;
Wilkinson’s catalyst was slowed by byproducts resulting
from the methylenation reaction (triphenylphosphine
oxide or remaining triphenylphosphine); thus, we tested
Walton, J. C. J. Chem. Soc., Perkin Trans. 1 2001, 3215-3229. (c)
Parsons, P. J.; Penkett, C. S.; Shell, A. J. Chem. Rev. 1996, 96, 195-
2
06. (d) Tietze, L. F. Chem. Rev. 1996, 96, 115-136.
(
2) Review: (a) Lee, J. M.; Na, Y.; Han, H.; Chang, S. Chem. Soc.
Rev. 2004, 33, 302-312. (b) Prestat, G.; Poli, G. Chemtracts 2004, 17,
7-103. A few examples have recently appeared in the literature: (c)
Siebeneicher, H.; Bytschkov, I.; Doye, S. Angew. Chem., Int. Ed. 2003,
2, 3042-3044. (d) Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.; Milton,
9
(5) Lebel, H.; Paquet, V. J. Am. Chem. Soc. 2004, 126, 11152-11153.
(6) Lebel, H.; Ladjel, C. J. Organomet. Chem. 2005, available online
31 May 2005.
(7) For examples of such transformations, see: (a) Ito, M.; Maeda,
M.; Kibayashi, C. Tetrahedron Lett. 1992, 33, 3765-3768. (b) Palomo,
C.; Aizpurua, J. M.; Ganboa, I.; Odriozola, B.; Urchegui, R.; Gorls, H.
Chem. Commun. 1996, 1269-1270. (c) Stragies, R.; Blechert, S. J. Am.
Chem. Soc. 2000, 122, 9584-9591. (d) Breit, B.; Zahn, S. K. Tetrahe-
dron 2005, 61, 6171-6179. (e) Boyer, F. D.; Ducrot, P. H. Tetrahedron
Lett. 2005, 46, 5177-5180.
(8) Osborn J. A.; Wilkinson, G. Inorg. Synth. 1990, 28, 77-79.
(9) (a) Young, J. F.; Osborn, J. A.; Jardine, F. H.; Wilkinson, G.
Chem. Commun. 1965, 131-132. (b) Osborn, J. A.; Jardine, F. H.;
Young, J. F.; Wilkinson, G. J. Chem. Soc. A 1966, 1711-1732. (c)
Jardine, F. H.; Osborn, J. A.; Wilkinson, G. J. Chem. Soc. A 1967,
1574-1578.
(10) (a) Haszeldine, R. N.; Parish, R. V.; Parry, D. J. J. Organomet.
Chem. 1967, 9, 13-14. (b) Wilkinson, G. Bull. Soc. Chim. Fr. 1968,
5055-5058. (c) Evans, D.; Osborn, J. A.; Wilkinson, G. J. Chem. Soc.
A 1968, 3133-3142. (d) Mannig, D.; Noth, H. Angew. Chem., Int. Ed.
Engl. 1985, 24, 878-879. (e) Pelter, A.; Beletskaya, I.; Pelter, A.
Tetrahedron 1997, 53, 4957-5026.
4
M. D.; Hidai, M.; Uemura, S. Angew. Chem., Int. Ed. 2003, 42, 2681-
2
4
2
684. (e) Cossy, J.; Bargiggia, F.; BouzBouz, S. Org. Lett. 2003, 5, 459-
62. (f) Ko, S.; Lee, C.; Choi, M. G.; Na, Y.; Chang, S. J. Org. Chem.
002, 68, 1607-1610. (g) Lemaire, S.; Prestat, G.; Giambastiani, G.;
Madec, D.; Pacini, B.; Poli, G. J. Organomet. Chem. 2003, 687, 291-
3
00. (h) Poli, G.; Giambastiani, G. J. Org. Chem. 2002, 67, 9456-9459.
(
i) Park, K. H.; Son, S. U.; Chung, Y. K. Org. Lett. 2002, 4, 4361-
4
363. (j) Son, S. U.; Park, K. H.; Chung, Y. K. J. Am. Chem. Soc. 2002,
1
24, 6838-6839. (k) Jeong, N.; Seo, S. D.; Shin, J. Y., J. Am. Chem.
Soc. 2000, 122, 10220-10221.
(3) (a) Paquet, V.; Lebel, H. Synthesis 2005, 1901-1905. (b) Lebel,
H.; Guay, D.; Paquet, V.; Huard, K. Org. Lett. 2004, 6, 3047-3050. (c)
Lebel, H.; Paquet, V. J. Am. Chem. Soc. 2004, 126, 320-328. (d) Lebel,
H.; Paquet, V. Org. Lett. 2002, 4, 1671-1674. (e) Grasa, G. A.; Moore,
Z.; Martin, K. L.; Stevens, E. D.; Nolan, S. P.; Paquet, V.; Lebel, H. J.
Organomet. Chem. 2002, 658, 126-131. (f) Lebel, H.; Paquet, V.;
Proulx, C. Angew. Chem., Int. Ed. 2001, 40, 2887-2890.
(
4) For a detailed mechanistic study, see ref 6c and: Lebel, H.;
Paquet, V. Organometallics 2004, 23, 1187-1190.
1
0.1021/jo0516741 CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/20/2005
J. Org. Chem. 2005, 70, 10159-10161
10159

TABLE 1. Optimization of the Rhodium-Catalyzed
yield (entry 5). Conversely, if the methylenation reaction
is performed in dioxane at 60 °C with excess of tri-
methylsilyldiazomethane and 2-propanol,3b followed by
the hydrogenation reaction at 14 atm of hydrogen, alkane
Methylenation-Hydrogenation Processa
12
8
was produced in 87% yield from the corresponding
ketone without the isolation of the alkene intermediate
eq 3).
entry
hydrogenation conditions
convb,c (%)
(
1
2
3
4
5
6
1 atm of H2/THF
e5
e5
1 atm of H2/dioxane
1 atm of H2, AlCl3/THF
1 atm of H2, H2O2/THF
1 atm of H2/hexanes
7 atm of H2/THF
e5
e5
e5
g98 (91)
a
Reaction Conditions: 5 mol % of RhCl(PPh3)3, 1.4 equiv of
b
TMSCHN2, 1.1 equiv of PPh3, 1.1 equiv of i-PrOH. Conversion
by GC-MS after 12 h of H2. Isolated yield in parentheses.
c
In conclusion, we have devised a new rhodium-
catalyzed methylenation hydrogenation process to syn-
thesize one-carbon homologated alkanes directly from
aldehydes and ketones with high efficiency.
TABLE 2. Rhodium-Catalyzed
a
Methylenation-Hydrogenation Process
Experimental Section
Typical Experimental Procedure for the Rhodium-
Catalyzed Methylenation-Hydrogenation of Aldehydes.
To a solution of chlorotris(triphenylphosphine)rhodium (0.046
g, 0.050 mmol) and triphenylphosphine (0.290 g, 1.10 mmol) in
THF (10.0 mL) in a hydrogenation pressure vessel was added
2
-propanol (0.084 mL, 1.10 mmol) followed by the aldehyde (1.00
mmol). To the resulting red mixture was added trimethylsilyl-
diazomethane (0.197 mL, 7.10 M, 1.40 mmol). Gas evolution was
observed, and the resulting mixture was stirred at room tem-
perature. When the methylenation was completed by TLC
analysis, the reaction mixture was purged with hydrogen,
pressurized at 100 psi (7 atm) of hydrogen, and then stirred for
1
2 h. After this time, the solvent was evaporated under reduced
pressure and the crude alkane was purifed by flash chromatog-
raphy using the indicated solvent.
tert-Butyl (R)-1-Phenylbutan-2-ylcarbamate (1). The title
compound was prepared from tert-butyl (S)-1-formyl-2-phenyl-
ethylcarbamate (0.240 g, 1.00 mmol) according to the typical
experimental procedure using 1 atm of hydrogen. The alkane 1
(
0.184 g, 77%) was obtained as a white solid after flash
chromatography (5% ethyl acetate/hexane): R 0.36 (5% ethyl
); H NMR (400 MHz,
) δ 7.32-7.28 (m, 2H), 7.24-7.19 (m, 3H), 4.33 (s (br), 1H),
.77 (s (br), 1H), 2.83-2.75 (m, 2H), 1.58-1.50 (m, 1H), 1.43 (s,
f
a
25
1
Reaction conditions: 5 mol % of RhCl(PPH3)3, 1.4 equiv of
acetate/hexane); [R]
CDCl
3
9
D 3
+5.00 (c 1.80, CHCl
b
TMSCHN2, 1.1 equiv of PPh3, 1.1 equiv of i-PrOH. Isolated yield.
3
1
3
H), 1.36-1.28 (m, 1H), 0.94 (t, J ) 8 Hz, 3H); C NMR (100
more basic solvent (dioxane, entry 2) and a number of
additives (entries 3 and 4) which could quench these
byproducts. However, no product 2 was observed with
these modifications. The use of hexane to precipitate
phosphine byproducts did not lead to a good result either
MHz, DMSO, 120 °C) δ 156.2, 140.5, 130.0, 128.9, 126.7, 78.6,
5
1
4.6, 41.7, 29.3, 28.1, 10.9; IR (neat) 3343, 2926, 1683, 1364,
167, 698 cm ; HMRS (ESI) calcd for C15H23NO Na [M + Na]
2
-1
+
272.1630, found 272.1621.
tert-Butyl(hexyloxy)dimethylsilane (2).13 The title com-
(
entry 5). Finally, simply increasing the pressure of
pound was prepared from 5-(tert-butyldimethylsilyloxy)-1-hexa-
nal (0.216 g, 1.00 mmol), according to the typical experimental
procedure. The alkane 2 (0.196 g, 91%) was obtained as a
colorless oil after flash chromatography (2% ethyl acetate/
hexane): R
hydrogen restored the catalytic activity of the rhodium
complex, and alkane 2 was isolated in 91% yield.
These reaction conditions were general and were used
to produce a variety of alkanes (Table 2). Both aliphatic
and aromatic aldehydes produced the corresponding
alkane in excellent yields from (entries 1-4). The hydro-
genation reaction conditions are mild enough to be
compatible with a variety of protecting groups including
benzyl ethers (entry 1). Hindered R-substituted aldehydes
1
f
0.75 (2% ethyl acetate/hexane); H NMR (400 MHz,
CDCl
3
) δ 3.62 (t, J ) 7 Hz, 2H), 1.56-1.49 (m, 2H), 1.37-1.27
13
(m, 6H), 0.92 (s (br), 12H), 0.07 (s, 6H); C NMR (100 MHz,
CDCl
3
) 63.3, 32.8, 31.6, 25.9, 25.4, 22.6, 18.3, 14.0, -5.26.
(
11) Surprisingly, the hydrogenation of the alkene derived from
Gardner’s aldehyde did not take place with 1 atm of hydrogen, although
this substrate contains a basic nitrogen group. Presumably, the ring
strain precludes the activation of Wilkinson’s catalyst.
are also converted to the corresponding alkane with
excellent yields (entries 3 and 4).11 As our methylenation
(12) Irino, T.; Otsuki, K. Chem. Pharm. Bull. 1975, 23, 646-650.
(13) Davies, J. S.; Higginbotham, C. L.; Tremeer, J.; Brown, B. J.
reaction is chemoselective for aldehydes over other car-
bonyl groups, ketone 7 was also isolated with a very good
Chem. Soc., Perkin Trans. 1 1992, 22, 3043-3048.
10160 J. Org. Chem., Vol. 70, No. 24, 2005

Acknowledgment. This research was supported by
NSERC (Canada), the Canadian Foundation for In-
novation, Boehringer Ingelheim (Canada) Lt e´ e, Merck
Frosst Canada, and the Universit e´ de Montr e´ al. Ac-
knowledgment is also made to the donors of the Ameri-
can Chemical Society Petroleum Research Fund for
partial support of this research.
Supporting Information Available: Characterization
1
13
data and spectra ( H and C NMR) for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JO0516741
J. Org. Chem, Vol. 70, No. 24, 2005 10161