J. Am. Chem. Soc. 1997, 119, 6949-6950
6949
Bu
3
SnH-Catalyzed Barton-McCombie
Deoxygenation of Alcohols
Rosa M. Lopez, David S. Hays, and Gregory C. Fu*
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, Massachusetts 02139
ReceiVed May 2, 1997
The Barton-McCombie procedure for the deoxygenation of
alcohols (Figure 1)1,2 is an extremely useful method that has
3
found widespread application in synthetic organic chemistry.
Figure 1. The Barton-McCombie deoxygenation reaction.
This radical-mediated process typically employs 1.5-3 equiv
of Bu3SnH as the reducing agent. In this paper, we describe
the first catalyzed variant of the Barton-McCombie deoxy-
genation reaction, using Bu3SnH as the catalyst and polymeth-
ylhydrosiloxane (PMHS; TMSO-(SiHMeO)n-TMS) as the sto-
ichiometric reductant (eq 1).
Figure 2. Proposed catalytic cycle for the Bu SnH-catalyzed Barton-
3
McCombie deoxygenation reaction.
Bu3SnH is an extraordinarily versatile reagent for organic
Sn(OPh) (Figure 2, left-hand side; cf. Figure 1);11 Bu3Sn(OPh)
then reacts with the stoichiometric reductant, M-H, to regener-
ate the Bu3SnH catalyst (Figure 2, right-hand side).
We chose to focus on the use of PMHS (TMSO-(SiHMeO)n-
TMS) as the stoichiometric reductant for our tin-catalyzed
4
synthesis. Unfortunately, some tributyltin-containing com-
5
pounds are toxic, a fact that has stimulated the development
of alternatives to Bu3SnH.6 Silicon hydrides have been the
primary focus of attention, and in a number of instances they
7
have been shown to serve as suitable substitutes for Bu3SnH.
Barton-McCombie process, based on the report of Itoi that
8
However, disparate reactivity has also been observed, as would
12
PMHS can reduce Bu3Sn(OPh) to Bu3SnH.
Furthermore,
be expected for fundamentally distinct families of compounds.
Rather than forsaking Bu3SnH due to concerns about toxicity,
we are developing processes in which it is employed as a
13
PMHS possesses the attributes of being nontoxic, easily
14
15
handled, and inexpensive.
We have successfully developed a Bu3SnH-catalyzed, PMHS-
mediated Barton-McCombie reaction based on the strategy
illustrated in Figure 2. Thus, treatment of a thionocarbonate
catalyst in conjunction with an innocuous stoichiometric re-
ductant.9
,10
This strategy allows us to exploit the well-
developed, sometimes unique, chemistry of Bu3SnH while
greatly diminishing the quantity of organotin residue that is
generated. The application of this approach to a Bu3SnH-
catalyzed variant of the Barton-McCombie deoxygenation
reaction is outlined in Figure 2. The reduction of a thionocar-
bonate by Bu3SnH affords COS, the desired alkane, and Bu3-
16
with 7.5 mol % of (Bu3Sn)2O, 5 equiv of PMHS, 5.5 equiv
of n-BuOH, and 2,2′-azobisisobutyronitrile (AIBN) in toluene
(
80-110 °C) provides the desired reduction product in good
17,18
yield (eq 1; Table 1, catalyzed),
for reactions that employ Bu3SnH as the stoichiometric reductant
comparable to that observed
19
(2.0 equiv; Table 1, stoichiometric). Thionocarbonates derived
from simple alcohols (entries 1 and 2), as well as from
carbohydrates (entries 3 and 4), are smoothly deoxygenated.
(
1) Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin Trans. 1
1
975, 1574-1585.
(
2) The use of phenyl thionocarbonate esters was pioneered by Robins:
(
a) Robins, M. J.; Wilson, J. S. J. Am. Chem. Soc. 1981, 103, 932-933.
(11) Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. C. Tetrahedron Lett.
1990, 31, 3991-3994.
(12) (a) Itoi, K. Fr. Pat. 1,368,522, 1964. (b) Itoi, K.; Kumano, S. Kogyo
Kagaku Zasshi 1967, 70, 82-86.
(
b) Robins, M. J.; Wilson, J. S.; Hansske, F. J. Am. Chem. Soc. 1983, 105,
4
059-4065.
(
3) (a) Hartwig, W. Tetrahedron 1983, 39, 2609-2645. (b) McCombie,
S. W. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.; Pergamon:
New York, 1991; Vol. 8, Chapter 4.2. (c) Crich, D.; Quintero, L. Chem.
ReV. 1989, 89, 1413-1432. (d) Pereyre, M.; Quintard, J.-P.; Rahm, A. Tin
in Organic Synthesis; Butterworths: Boston, 1987; Chapter 5.
(13) Klyaschitskaya, A. L.; Krasovskii, G. N.; Fridlyand, S. A. Gig. Sanit.
1970, 35, 28-31; Chem. Abst. 1970, 72, 124864r. LD50 of PMHS: 80 g/kg.
(14) In contrast to Bu3SnH, PMHS is neither air- nor moisture-sensitive.
(15) Prices from Aldrich Chemical Company (Milwaukee, WI), per mole
of hydride: PMHS $6; Bu3SnH $250; (Me3Si)3SiH $1300.
(
4) For reviews of the chemistry of Bu3SnH, see: (a) Neumann, W. P.
Synthesis 1987, 665-683. (b) RajanBabu, T. V. In Encyclopedia of Reagents
(16) Based on a hydride equivalent weight of 60 g/mol.
for Organic Synthesis; Paquette, L. A., Ed.; Wiley: New York, 1995.
(17) Sample experimental (Table 1, entry 2): PMHS (300 mg, 5.00
mmol), n-butanol (500 µL, 5.46 mmol), AIBN (25 mg, 0.15 mmol), and
(Bu3Sn)2O (19 µL, 0.037 mmol) were added to a solution of thionocarbonate
(364 mg, 1.00 mmol) in toluene (1.0 mL). The resulting solution was stirred
at 80 °C for 8 h, and then more (Bu3Sn)2O (19 µL, 0.037 mmol) and AIBN
(25 mg, 0.15 mmol) were added. After an additional 16 h of stirring at 80
°C, the reaction mixture was cooled to room temperature and diluted with
THF (10 mL). Aqueous 2 N NaOH (10 mL) was added slowly to the rapidly
stirring solution. After 8 h, the reaction mixture was extracted with Et2O
(2 × 15 mL), and the combined organic layers were washed (1 N HCl, 2
× 10 mL; brine, 1 × 15 mL), dried, and concentrated. The product was
purified by flash chromatography (1% EtOAc/hexanes), affording 165 mg
(71%) of a colorless oil.
(
5) Boyer, I. J. Toxicology 1989, 55, 253-298.
(
6) For a succinct discussion, see: Crich, D.; Sun, S. J. Org. Chem. 1996,
6
1, 7200-7201.
(
7) For an overview of the use of silanes as reducing agents in the
Barton-McCombie deoxygenation, see: Chatgilialoglu, C.; Ferreri, C. Res.
Chem. Intermed. 1993, 19, 755-775. See also: Barton, D. H. R.; Jang, D.
O.; Jaszberenyi, J. C. J. Org. Chem. 1993, 58, 6838-6842.
(
8) For example, see: (a) Reference 7. (b) Apeloig, Y.; Nakash, M. J.
Am. Chem. Soc. 1994, 116, 10781-10782. (c) Ballestri, M.; Chatgilialoglu,
C.; Lucarini, M.; Pedulli, G. F. J. Org. Chem. 1992, 57, 948-952.
(
9) (a) Hays, D. S.; Fu, G. C. J. Org. Chem. 1996, 61, 4-5. (b) Hays,
D. S.; Scholl, M.; Fu, G. C. J. Org. Chem. 1996, 61, 6751-6752.
10) 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,
-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.
(
(18) Notes: (a) These reactions were not individually optimized. (b) In
no instance did we experience any difficulty with tin contamination of our
products, a problem often encountered in reactions that employ stoichio-
metric quantities of Bu3SnH (ref 6 and 19b).
1
S0002-7863(97)01400-5 CCC: $14.00 © 1997 American Chemical Society