Cooperative Catalysis of Samarium Diiodide and Mercaptan in a Stereoselective One-pot Transformation of 5-oxopentanals into δ-lactones

Article abstract of DOI:10.1021/ol9911526

(Matrix Presented) We demonstrate a general method for conversion of various 5-oxopentanals to substituted δ-lactones and 1-oxa-2-decalones by the synergistic catalysis of samarium diiodide and 2-propanethiol (or disulfide). The deliberate use of mercaptan is advantageous to facilitate the catalytic cycle. This method shows high stereoselectivities, and an enantioselective procedure is feasible by using the chiral mercaptan (1R,2S)-1-phenyl-2-(N-acetamido)propanethiol as a promoter.

Full text of DOI:10.1021/ol9911526

ORGANIC
LETTERS
1999
Vol. 1, No. 12
1989-1991
Cooperative Catalysis of Samarium
Diiodide and Mercaptan in a
Stereoselective One-Pot Transformation
of 5-Oxopentanals into δ-Lactones
Jue-Liang Hsu, Chao-Tsen Chen, and Jim-Min Fang*
Department of Chemistry, National Taiwan UniVersity, Taipei, Taiwan 106,
Republic of China
jmfang@mail.ch.ntu.edu.tw
Received October 16, 1999
ABSTRACT
We demonstrate a general method for conversion of various 5-oxopentanals to substituted δ-lactones and 1-oxa-2-decalones by the synergistic
catalysis of samarium diiodide and 2-propanethiol (or disulfide). The deliberate use of mercaptan is advantageous to facilitate the catalytic
cycle. This method shows high stereoselectivities, and an enantioselective procedure is feasible by using the chiral mercaptan (1R,2S)-1-
phenyl-2-(N-acetamido)propanethiol as a promoter.
Many natural products, such as insect pheromones and food
flavors, incorporate the core structure of δ-lactones, which
also attract a number of synthetic approaches.1 Uenishi and
co-workers2 have demonstrated that 5-oxo-4-silyloxyhexanals
can undergo the intramolecular Tishchenko oxidoreductions3
by reactions with stoichiometric amounts of (t-BuO)SmI2 or
an aged SmI2 solution (presumably containing Sm3+ ion) to
give the corresponding δ-lactones. The authors also indicated
that the silyloxy substituent is essential for such transforma-
tions. Otherwise, unsubstituted substrates such as 5-oxo-
hexanal afford only low yields (∼10%) of δ-methyl-δ-lactone
on treatment with (t-BuO)SmI2 or simply the pinacolic
coupling product on treatment with a freshly prepared SmI2
solution. We found previously3e that transformation of
5-trimethylsilyl-5-oxopentanal into δ-trimethylsilyl-δ-lactone
can be carried out by using stoichiometric amounts of SmI2
and methanol. This reaction is presumably initiated by
addition of MeOH to the aldehyde group to form a hemi-
acetal with the assistance of samarium ion. After an
intramolecular hydride transfer to the ketone group (Tish-
chenko reaction),3 a cyclization of the δ-hydroxyester
intermediate would give the observed δ-lactone product. On
the basis of this speculation, one can conceive a catalytic
method for transformation of 5-oxopentanals into their
(1) (a) Ohloff, G. Fortschr. Chem. Org. Naturst. 1978, 35, 431. (b)
Mulzer, J. In ComprehensiVe Organic Functional Group Transformations;
Katrizky, A. R., Meth-Cohn, O., Rees, C. W., Eds.; Elsevier: Oxford, 1995;
Vol. 5, pp 121-179. (c) Ley, S. V.; Cox, L. R.; Meek, G. Chem. ReV.
1996, 96, 423. (d) Collins, I. J. Chem. Soc., Perkin Trans. 1 1998, 1869.
(2) Uenishi, J.; Masuda, S.; Wakabayashi, S. Tetrahedron Lett. 1991,
32, 5097.
(3) Examples of samarium ion catalyzed Tishchenko reactions: (a) Collin,
J.; Namy, J. L.; Kagan, H. B. NouV. J. Chem. 1986, 10, 229. (b) Evans, D.
A.; Hoveyda, A. H. J. Am. Chem. Soc. 1990, 112, 6447. (c) Curran, D. P.;
Wolin, R. L. Synlett 1991, 317. (d) Molander, G. A.; McKie, J. A. J. Am.
Chem. Soc. 1993, 115, 5821. (e) Chuang, T.-H.; Fang, J.-M.; Jiaang, W.-
T.; Tsai, Y.-M. J. Org. Chem. 1996, 61, 1794. (f) Lu, L.; Chang, H.-Y.;
Fang, J.-M. J. Org. Chem. 1999, 64, 843.
10.1021/ol9911526 CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/10/1999

corresponding δ-lactones. Indeed, we report herein a general
and efficient one-pot procedure by using SmI2 and 2-pro-
panethiol (i-PrSH) as the combined catalysts.
As shown in Scheme 1, a series of 5-alkyl- and 5-phenyl-
5-oxopentanals 1a-g were successfully converted to the
modified procedure by premixing an aliquot of SmI2/i-PrSH
(1-5 mol % in 1 mL of THF) with the substrate (1a-g) in
an oven-dried syringe. The resulting yellow solution, an
indication of the presence of trivalent samarium ion, was
then added dropwise to the original SmI2/i-PrSH solution.
Accordingly, the desired lactones 2a-g were also obtained
in excellent yields (>90%).
By replacing SmI2/i-PrSH with SmI2/(MeS)2,5 the reaction
of 1e (R ) n-C8H17) also proceeded smoothly to give 2e in
a comparable yield. The in situ generated (MeS)SmI2 was
considered as the reactive catalyst.5 By using SmI3/i-PrSH
instead of SmI2/i-PrSH, the reaction gave a 1:1 mixture of
isopropyl thioesters of tridec-4-enoic acid and tridec-5-enoic
acid according to NMR analysis. It seemed that the inter-
mediary δ-oxyacid thioester (analogue of B in Figure 1, R
Scheme 1
corresponding δ-substituted-δ-lactones 2a-g4 by the cataly-
sis of SmI2/i-PrSH (10-50 mol %). No aldol or pinacol
products were observed under these reaction conditions.
The following procedure is typical. Under an atmosphere
of argon, i-PrSH (0.01 mL, 0.1 mmol) was added to a deep
blue SmI2 (0.2 mmol) solution freshly prepared from
samarium and 1,2-diiodoethane in THF (15 mL). The mixture
was stirred for 10 min at room temperature, and a THF
solution (5 mL) of 5-oxo-5-phenylpentanal (1c, 176 mg, 1.0
mmol) was added dropwise. The mixture was stirred for 1 h
and then filtered through a short silica gel column by elution
with EtOAc/hexane (1:1). The filtrate was concentrated by
rotary evaporation to give the practically pure lactone 2c (174
mg, 99%). We also conducted reactions using a slightly
Figure 1. Proposed catalytic cycle and the favorable transition
states for the formation of δ-lactones.
) n-C8H17) was diverted to dehydration under such reaction
conditions.6 The reaction of 1c (R ) Ph) with stoichiometric
amounts of SmI3 and i-PrSH also gave an 83% yield of
5-phenylpent-4-enoic acid isopropyl thioester.6 When 1c was
treated with stoichiometric amounts of SmI2 and i-PrOH, a
1990
Org. Lett., Vol. 1, No. 12, 1999

1:1 mixture of isopropyl 5-hydroxy-5-phenylpentanoate and
1-phenyl-1,2-cyclopentanediol were obtained as a conse-
quence of the intramolecular Tishchenko oxidoreduction and
pinacolic coupling.
catalyzed reactions of 2-(3-oxopropyl)cyclohexanones 6a,b
at 25 °C afforded 1-oxa-2-decalones 10a,b in a preponder-
ance of the 9,10-trans isomers.4l,m,8 The trans decalones had
H-9 and H-10 at axial positions as characterized by the ddd
1
splitting pattern (J ) 10, 10, 4 Hz) of H-9 in the H NMR
On the basis of the above experimental results, one can
propose a possible reaction mechanism for the formation of
δ-lactones (Figure 1). A Lewis acid such as the presumed
(i-PrS)SmI2 or the related samarium species3a,5,7 can promote
the addition of i-PrSH to the aldehyde group of a 5-oxo-
pentanal substrate. The samarium-bound hemithiolacetal
intermediate (A) can undergo an intramolecular hydride shift
to give the δ-oxyacid thioester (B).3d The reaction would
proceed further with an irreversible lactonization and release
the catalyst (i-PrS)SmI2 (or the related samarium species)
for the next cycle. The deliberate use of mercaptan is
advantageous, because mercaptan is a better nucleophile than
alcohol on addition to the aldehyde group. The resulting
thioester is also more reactive than ester in the subsequent
lactonization; thus the catalytic cycle is facilitated.
The SmI2/i-PrSH-catalyzed reaction of bulky substrate 3
still proceeded smoothly to give δ-lactone 7 (Scheme 1).4h
A variety of substituted 5-oxopentanals 4-6 also underwent
the SmI2/i-PrSH catalyzed reactions in highly stereoselective
manners. Lactones 8a,b,4i,j derived from 4-methyl-5-oxo-
pentanals 4a,b, had the cis configuration as indicated by a
small coupling constant (∼3 Hz) between H-5 and H-6.
Treatment of 3-methyl-5-oxo-5-phenylpentanal (5) in an
SmI2/i-PrSH solution at 25 °C gave lactone 9 as a mixture
of trans and cis isomers (77:23).4k The trans/cis isomeric
ratio was increased substantially to 94:6 by performing the
reaction at a lower temperature (0 °C). The trans lactone
showed an NOE correlation between Me-4 and H-6, whereas
the cis isomer was devoid of this effect. The SmI2/i-PrSH-
spectra.4
The stereochemical outcomes can be interpreted by
comparisons of the transition states C versus D and E versus
F (Figure 1). The transition state C, giving cis-8a,b and
trans-9, is energetically favored due to the equatorial
dispositions of substituents (R1 or R2), whereas the alternative
transition state D exerts steric repulsions due to the axially
oriented substituents. The transition state E, giving trans-
10a,b by having hydride attack the cyclohexanone moiety
from the axial direction, is superior to an equatorial attack
in the transition state F. Under such circumstances, a product
development control also favors the formation of the more
stable equatorial alcohol (as shown in E). The stereoselec-
tivities are in agreement with the previous findings3c,f of the
related intermolecular Tishchenko reactions.
Our current study demonstrates an effective stereocontrol
in conversion of 5-oxopentanals to δ-lactones by the
synergistic catalysis of 2-propanethiol and samarium ion.
This study also sheds light on the design of enantioselective
catalysis by using chiral mercaptans. Our preliminary result
using SmI2 and (1R,2S)-1-phenyl-2-(N-acetamido)propan-
ethiol as the combined catalysts (50 mol %) indicated that
5-octyl-5-oxopentanal (1e) was converted to 6-octyl-3,4,5,6-
tetrahydropyran-2-one (2e) with predominance of the (R)-
(+)-enantiomer (52% ee according to the HPLC analysis on
a Chiralcel OB column).
Acknowledgment. We thank the National Science Coun-
cil for financial support.
(4) All the δ-lactones 2a-g, 7, 8a,b, 9, and 10a,b are fully characterized
by spectral methods (IR, MS, HRMS, 1H and 13C NMR). (a) White, J. D.;
Somers, T. C.; Reddy, G. N. J. Org. Chem. 1992, 57, 4991, for compound
2a. (b) Utaka, M.; Watabu, H.; Takeda, A. J. Org. Chem. 1987, 52, 4363,
for compounds 2b and 2e. (c) Downham, R.; Edwards, P. J.; Entwistle, D.
A.; Hughes, A. B.; Kim, K. S.; Ley, S. V. Tetrahedron: Asymmetry 1995,
6, 2403, for compound 2c. (d) Barluenga, J.; Lopez, P. J.; Campos, J. A.
Tetrahedron 1983, 39, 2863, for compound 2d. (e) Haase, B.; Schneider,
M. P. Tetrahedron: Asymmetry 1993, 4, 1017, for compound (R)-2e. (f)
Otsubo, K.; Kawamura, K.; Inanaga, J.; Yamaguchi, M. Chem. Lett. 1987,
1487, for compound 2f. (g) Garner, P.; Anderson, J. T. Tetrahedron Lett.
1997, 38, 6647, for compound 2g. (h) Souma, Y.; Iyoda, J.; Sano, H. Bull.
Chem. Soc. Jpn. 1976, 49, 3291, for compound 7. (i) Kobayashi, Y.; Kitano,
Y.; Takeda, Y.; Sato, F. Tetrahedron 1986, 42, 2937, for compound 8a. (j)
Oshima, M.; Yamazaki, H.; Shimizu, I.; Nisar, M.; Tsuji, J. J. Am. Chem.
Soc. 1989, 111, 6280, for compound 8b. (k) Barbero, A.; Blakemore, D.
C.; Fleming, I.; Wesley, R. N. J. Chem. Soc., Perkin Trans. 1 1997, 1329,
for compound 9. (l) Griffiths, D. V.; Wilcox, G. J. Chem. Soc., Perkin
Trans. 2 1988, 431, for compound 10a. (m) Edward, J. T.; Cooke, E.;
Paradellis, T. C. Can. J. Chem. 1982, 60, 2546, for compound 10b. The
data relevant to the stereochemical assignments are shown: 2e, the (R)-
enantiomer, [R]D ) +38.4 (CHCl3), is more retained than the (S)-enantiomer
on a Chiralcel OB column by elution with i-PrOH/hexane (2:98); 2g, δH
3.85 (1 H, dd, J ) 11.7 Hz, J ) 2.8 Hz); 8a (cis), δH 4.14 (ddd, J ) 11.5,
OL9911526
5.5, 2.8 Hz, H-6); 8b (cis), 5.48 (d, J ) 3.0 Hz, H-6); trans-9, δH 1.09 (d,
J ) 6.2 Hz, Me-4), 5.50 (dd, J ) 7.3, 4.6 Hz, H-6); cis-9, δH 1.07 (d, J )
6.4 Hz, Me-4), 5.29 (dd, J ) 12.0, 3.1 Hz, H-6); trans-10a, δH 3.28 (ddd,
J ) 10.2, 10.2, 4.2 Hz, H-9); cis-10b, δH 4.44 (br dd, J ) 6.7, 3.3 Hz,
H-9); trans-10b, δH 3.80 (ddd, J ) 10.5, 10.4, 4.5 Hz, H-9); cis-10b, δH
4.42 (br d, J ) 2.6 Hz, H-9).
(5) The S-S bond of PhSSPh is reductively cleaved by SmI2, see: (a)
Jia, X.; Zhang, Y.; Zhou, X. Synth. Commun. 1994, 24, 387. (b) Taniguchi,
Y.; Maruo, M.; Takaki, K.; Fujiwara, Y. Tetrahedron Lett. 1994, 35, 7789.
(6) The reason for the preference of dehydration was unclear, presumably
due to SmI3 exhibiting a property of stronger Lewis acid.
(7) It has been reported (ref 3a) that SmI2 reacts with alcohol ROH to
give (RO)SmI2 in the presence of a metallic salt as the electron carrier.
(8) Chandrasekhar, S.; Venkatesan, V. J. Chem. Res, Miniprint 1995,
1137. The authors reported that 2-(3-oxopropyl)cyclohexanone (6a) under-
went an intramolecular Cannizzaro reaction in boiling NaOH solution to
give 3-(2-hydroxycyclohexyl)propionic acid, which was subjected to
lactonization on treatment with concentrated HCl to give exclusively the
trans isomer of 10a (59%), based on an analysis of the 1H NMR spectrum
(90 MHz). In our hand, the two-step reaction afforded a trans/cis mixture
of 10a in a ratio of 91:9 based on an analysis of the 1H NMR spectrum
(300 MHz).
Org. Lett., Vol. 1, No. 12, 1999
1991