Bu3SnH-Catalyzed Reduction of Nitroalkanes to Alkanes

Full text of DOI:10.1021/jo980789k

5296
J . Org. Chem. 1998, 63, 5296-5297
Communications
Bu 3Sn H-Ca ta lyzed Red u ction of Nitr oa lk a n es
to Alk a n es
J ordi Tormo, David S. Hays, and Gregory C. Fu*
Department of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139
Received April 28, 1998
Since its discovery by Ono and Tanner in 1981,1 the
radical-mediated reduction of nitroalkanes to alkanes with
stoichiometric Bu3SnH has become the most widely em-
ployed method for effecting this useful transformation.2-5
Because of the toxicity of certain tributyltin compounds,6 as
well as the purification problems that often accompany the
use of Bu3SnH,7 the development of equally efficient,
alternate methods that diminish the need for Bu3SnH has
obvious significance. Although silicon hydrides, in particular
(Me3Si)3SiH, can serve as substitutes for Bu3SnH in a
number of radical-mediated processes,8 Chatgilialoglu has
established that (Me3Si)3SiH cannot effect the reduction of
nitroalkanes to alkanes.9
We have recently reported the development of Bu3SnH-
catalyzed variants of several families of reactions that had
previously been achieved with stoichiometric Bu3SnH.10,11
In the catalytic cycle for these processes, the first elementary
steps involve the known stoichiometric reduction chemistry
of Bu3SnH, and the subsequent steps effect regeneration of
the Bu3SnH catalyst with an otherwise innocuous reductant.
In this paper, we establish that this strategy can be applied
to the conversion of nitroalkanes to alkanes, using 10%
Bu3SnH as the catalyst and PhSiH3 as the stoichiometric
reducing agent (eq 1).
F igu r e 1. Proposed catalytic cycle for the Bu3SnH-catalyzed
reduction of nitroalkanes to alkanes.
catalytic cycle for the Bu3SnH-catalyzed reduction of a
nitroalkane to an alkane. Initially, reaction of a nitroalkane
with 1 equiv of Bu3SnH produces an alkane and Bu3SnONO
(Figure 1, “stoichiometric reaction”).1,4 In the regeneration
phase of the catalytic cycle, a second metal hydride (M-H)
reduces Bu3SnONO to Bu3SnH (Figure 1, “turnover step”).
In our earlier work on Bu3SnH-catalyzed processes, we
established that, for reactions that produce Bu3SnOR in the
“stoichiometric reaction” phase of the catalytic cycle, silanes
(M-H ) Si-H) serve as effective reducing agents in the
“turnover step.”10 Because others had shown that the re-
duction of Sn-O bonds by silanes proceeds more slowly as
the oxygen becomes less basic,12 we were initially somewhat
pessimistic about the likelihood that a silane would be able
to reduce Bu3SnONO to Bu3SnH. In the case of nitroalkane
reduction, the thermal instability of Bu3SnONO (almost
complete decomposition after several hours at 60 °C)13 places
a stringent requirement on the efficiency of the turnover
step. Fortunately, our concern proved to be unfounded:
Treatment of Bu3SnONO with PhSiH3 at room temperature
leads to immediate and quantitative formation of Bu3SnH
(eq 2).14
Figure 1 provides a simplified version of a potential
Coupled with the previously reported stoichiometric reac-
tion, this new Bu3SnH-forming process provides the basis
for a catalytic method for the reduction of nitroalkanes to
alkanes (Figure 1). Thus, treatment of any of a variety of
substrates with 10% Bu3SnH and 0.5 equiv of PhSiH3 in
refluxing toluene furnishes the desired alkane in good yield
(Table 1; catalyzed);15-17 in the absence of Bu3SnH under
(1) (a) Ono, N.; Miyake, H.; Tamura, R.; Kaji, A. Tetrahedron Lett. 1981,
22, 1705-1708. (b) Tanner, D. D.; Blackburn, E. V.; Diaz, G. E. J . Am. Chem.
Soc. 1981, 103, 1557-1559.
(2) Based on a search of the Beilstein Crossfire database.
(3) For a review, see: Ono, N.; Kaji, A. Synthesis 1986, 693-704. See
also: Larock, Richard C. Comprehensive Organic Transformations; VCH:
New York, 1989; p 26.
(4) For mechanistic studies, see: (a) Dupuis, J .; Giese, B.; Hartung, J .;
Leising, M.; Korth, H.-G.; Sustmann, R. J . Am. Chem. Soc. 1985, 107, 4332-
4333. Korth, H.-G.; Sustmann, R.; Dupuis, J .; Giese, B. Chem. Ber. 1987,
120, 1197-1202. (b) Kamimura, A.; Ono, N. Bull. Chem. Soc. J pn. 1988,
61, 3629-3635. (c) Tanner, D. D.; Harrison, D. J .; Chen, J .; Kharrat, A.;
Wayner, D. D. M.; Griller, D.; McPhee, D. J . J . Org. Chem. 1990, 55, 3321-
3325.
(11) For the work of others, see: (a) Nitzsche, S.; Wick, M. Angew. Chem.
1957, 69, 96. Lipowitz, J .; Bowman, S. A. Aldrichim. Acta 1973, 6, 1-6. (b)
Corey, E. J .; Suggs, J . W. J . Org. Chem. 1975, 40, 2554-2555. Stork, G.;
Sher, P. M. J . Am. Chem. Soc. 1986, 108, 303-304.
(5) For applications of nitroalkanes in organic synthesis, see: Rosini, G.;
Ballini, R. Synthesis 1988, 833-847.
(12) (a) Itoi, K. Fr. Patent 1,368,522, 1964. Itoi, K.; Kumano, S. Kogyo
Kagaku Zasshi 1967, 70, 82-86. (b) Hayashi, K.; Iyoda, J .; Shiihara, I. J .
Organomet. Chem. 1967, 10, 81-94. (c) Pijselman, J .; Pereyre, M. J .
Organomet. Chem. 1973, 63, 139-157. (d) See also ref 10a.
(13) Kobayashi, K.; Kwanisi, M.; Kozima, S. Synth. React. Inorg. Met.-
Org. Chem. 1978, 8, 75-82.
(6) (a) De Mora, S. J . Tributyltin: Case Study of an Environmental
Contaminant; Cambridge University Press: Cambridge, UK, 1996. (b)
Boyer, I. J . Toxicology 1989, 55, 253-298.
(7) For a succinct overview, see: Crich, D.; Sun, S. J . Org. Chem. 1996,
61, 7200-7201.
(14) In contrast, polymethylhydrosiloxane (TMSO-(SiHMeO)n-TMS;
PMHS) is ineffective for this reduction.
(8) For a review, see: Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188-
194.
(15) Experimental procedure: A solution of Bu3SnH (0.026 mL, 0.10
mmol), PhSiH3 (0.061 mL, 0.50 mmol), and 1,1′-azobis(cyclohexanecarbo-
nitrile) (ACHN; 49 mg, 0.20 mmol) in toluene (0.3 mL) was added to a
solution of the nitroalkane (1.00 mmol) in toluene (0.2 mL). The resulting
mixture was immersed in a 110 °C oil bath and stirred for 5 h. Additional
ACHN (49 mg, 0.20 mmol) was then added, and the mixture was stirred
for 3 more hours at 110 °C. The reaction product was then purified by flash
chromatography.
(9) Ballestri, M.; Chatgilialoglu, C. J . Org. Chem. 1992, 57, 948-952.
(10) (a) Barton-McCombie deoxygenation of alcohols: Lopez, R. M.;
Hays, D. S.; Fu, G. C. J . Am. Chem. Soc. 1997, 119, 6949-6950. (b)
Reduction of azides: Hays, D. S.; Fu, G. C. J . Org. Chem. 1998, 63, 2796-
2797. (c) Reductive cyclization of enals and enones: Hays, D. S.; Fu, G. C.
J . Org. Chem. 1996, 61, 4-5. (d) Conjugate reduction of enones: Hays, D.
S.; Scholl, M.; Fu, G. C. J . Org. Chem. 1996, 61, 6751-6752.
S0022-3263(98)00789-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/11/1998

Communications
J . Org. Chem., Vol. 63, No. 16, 1998 5297
Ta ble 1. Bu 3Sn H-Ca ta lyzed Red u ction of Nitr oa lk a n es
to Alk a n es (Eq 1)
otherwise identical conditions, <10% reduction is observed.
Importantly, the new catalytic reaction proceeds with ef-
ficiency comparable to the stoichiometric Bu3SnH method
(Table 1). Like the stoichiometric method, the catalytic
reaction is effective for the reduction of tertiary nitroalkanes
and activated secondary nitroalkanes and is compatible with
functionality such as ethers, acetals, ketones, esters, nitriles,
and mesylates.3
For the reduction of the TBS ether of 2-methyl-2-nitro-1-
propanol (Table 1, entry 1), we have determined that the
concentration of Bu3SnH remains constant throughout the
course of the reaction, consistent with our understanding
of the catalytic cycle. Reduction of this substrate on a 4-g
scale provides a 71% yield of the alkane (eq 3), illustrating
the practicality of the new catalytic process.
In conclusion, we have described the development of a
new Bu3SnH-catalyzed method for the reduction of nitroal-
kanes to alkanes. The catalytic cycle is based on a known
stoichiometric reaction and a previously unknown catalyst-
regeneration step. We have established that the catalytic
process is comparable to the stoichiometric in terms of
efficiency and that it is amenable to scale-up. In view of
the fact that the conversion of nitroalkanes to alkanes is
currently most often accomplished with stoichiometric
Bu3SnH, we anticipate that this environmentally friendlier,
Bu3SnH-catalyzed variant may become the method of choice
for effecting this important transformation.
a
b
Average of two runs. (1) 10% Bu3SnH, 0.5 equiv of PhSiH3,
0.2 equiv of ACHN, toluene, 110 °C, 5 h; (2) 0.2 equiv of ACHN, 3
h. c (1) 1.5 equiv of Bu3SnH, 0.2 equiv of ACHN, toluene, 110 °C,
d
5 h; (2) 0.2 equiv of ACHN, 3 h. Yields by GC vs an internal
standard: catalytic Bu3SnH, 90%; stoichiometric Bu3SnH, 93%.
e These reactions were run at 80 °C with AIBN as the initiator.
f Based on 76% conversion. This reaction is slower than the
catalytic reaction, due to the low solubility of the substrate under
the stoichiometric reduction conditions. g These reactions were run
at 80 °C with AIBN as the initiator (8 h for the catalytic reaction;
2 h for the stoichiometric reaction). The yields were measured by
GC vs an internal standard.
Ack n ow led gm en t. Support has been provided by the
Alfred P. Sloan Foundation, the American Cancer Society,
the Camille and Henry Dreyfus Foundation, Eli Lilly,
Firmenich, Glaxo Wellcome, the National Science Founda-
tion (predoctoral fellowship to D.S.H.; Young Investigator
Award, with funding from Merck, Pharmacia & Upjohn,
Bristol-Myers Squibb, DuPont, Bayer, Rohm & Haas, and
Novartis), Pfizer, Procter & Gamble, the Research Corpo-
ration, and the Spanish Ministry of Education (postdoctoral
fellowship to J .T.). Acknowledgment is made to the donors
of the Petroleum Research Fund, administered by the ACS,
for partial support of this research.
(16) Reductions can be achieved with lower catalyst loadings, but longer
reaction times are required. The use of smaller amounts of initiator
sometimes leads to incomplete reduction.
(17) In several of our earlier studies of Bu3SnH-catalyzed reactions, we
established that the presence of a primary alcohol can facilitate regeneration
of Bu3SnH (ref 10a-c). However, added primary alcohol is detrimental in
the case of Bu3SnH-catalyzed reductions of nitroalkanes to alkanes
(possibly due to the formation of HNO2).
Su p p or tin g In for m a tion Ava ila ble: Experimental proce-
dures and compound characterization data (8 pages).
J O980789K