Iron-promoted elimination of β-thioalkoxy alcohols. Olefination by coupling of a carbonyl group with a dithioacetal

Article abstract of DOI:10.1021/ol701579f

Treatment of propargylic dithiolanes with ⁿBuLi followed by a carbonyl electrophile yields the corresponding propargylic dithioacetals. Upon treatment with 1 equiv of Fe(BCaC)₃ and excess MeMgl, elimination of SR and OH moieties from 8 affords the corresponding olefins in satisfactory yield. Benzylic dithioacetals behave similarly. The reaction can be considered an alternative of McMurry coupling of two different carbonyl equivalents.

Full text of DOI:10.1021/ol701579f

ORGANIC
LETTERS
2007
Vol. 9, No. 18
3663-3665
Iron-Promoted Elimination of
-Thioalkoxy Alcohols. Olefination by
Coupling of a Carbonyl Group with a
Dithioacetal
â
Li-Fu Huang, Chih-Wei Chen, and Tien-Yau Luh*
Department of Chemistry, National Taiwan UniVersity, Taipei 106, Taiwan
tyluh@ntu.edu.tw
Received July 5, 2007
ABSTRACT
Treatment of propargylic dithiolanes with nBuLi followed by a carbonyl electrophile yields the corresponding propargylic dithioacetals. Upon
treatment with 1 equiv of Fe(acac)3 and excess MeMgI, elimination of SR and OH moieties from 8 affords the corresponding olefins in satisfactory
yield. Benzylic dithioacetals behave similarly. The reaction can be considered an alternative of McMurry coupling of two different carbonyl
equivalents.
Elimination of two vicinal heteroatom substituents X and Y
provides a useful regio- and stereoselective protocol for the
synthesis of olefins.1-7 This kind of transformation would
be particularly practical if the heteroatom-substituted starting
materials are readily accessible. Elimination of vicinal
dihalides,2 Corey-Winter reaction,3 and deoxygenation of
epoxides4 are well-documented. Alternatively, the hetero-
atom-containing precursors can be generated in situ from
the corresponding carbonyl compounds. Wittig and Horner-
Wadsworth-Emmons reactions,5 Peterson olefination,6 and
Kociensky-Julia synthesis of trans-olefins,7 inter alia, are
typical examples. It is known that a â-thioalkoxy alcohol
can be conveniently obtained from the reaction of a sulfur-
stabilized carbanion with a carbonyl compound.8 Simulta-
neous elimination of vicinal thioalkoxy and hydroxyl groups
leading to the formation of olefin has been sporadically
explored.9 It is known that a carbon-sulfur bond can be
activated by a low valent transition metal catalyst.10 Numer-
ous examples on â-heteroatom elimination of a σ-metal-
alkyl complex or intermediate under various conditions are
known.11,12 We recently reported that activated dithiolanes
(1) (a) Smith, M. B.; March, J. March’s AdVanced Organic Chemistry:
Reactions, Mechanisms and Structure, 6th ed.; Wiley: Hoboken, 2007; pp
1534-1546. (b) Bruckner, R. AdVanced Organic Chemistry: Reaction
Mechanisms; Harcourt: San Diego, 2002; pp 160-167. (c) Concello´n, J.
M.; Rodr´ıguez-Solla, H. Chem. Soc. ReV. 2004, 33, 599. (d) Shinokubo,
H.; Oshima, K. Synlett 2000, 322.
(2) (a) Percy, J. M. In ComprehensiVe Organic Functional Group
Transformations; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.;
Pergamon: Oxford, 1995; Vol. 1 (Roberts, S. M., Ed.), pp 553-587. (b)
Piva, O. In ComprehensiVe Organic Functional Group Transformations
II; Katritzky, A. R., Taylor, R. J. K., Eds.; Pergamon: Oxford, 2005; Vol.
1 (Cossy, J., Ed.), pp 586-600.
(3) Corey, E. J.; Winter, A. E. J. Am. Chem. Soc. 1963, 85, 2677.
(4) For a review, see: Wong, H. N. C.; Fok, C. C. M.; Wong, T.
Heterocycles 1987, 26, 1345.
(5) For reviews, see: (a) Maercker, A. Org. React. 1965, 14, 270. (b)
Wadsworth, W. S. Org. React. 1977, 25, 73. (c) Maryanoff, B. E.; Reitz,
A. B. Chem. ReV. 1989, 89, 863. (d) Shen, Y.-C. Acta Chim. Sin. 2000, 58,
253.
(6) For reviews, see: (a) Peterson, D. J. J. Org. Chem. 1968, 33, 780.
(b) Ager, D. J. Org. React. 1990, 38, 1. (c) Barrett, A. G. M.; Hill, J. M.;
Wallace, E. M.; Flygare, J. A. Synlett 1991, 764. (d) van Staden, L. F.;
Gravestock, D.; Ager, D. J. Chem. Soc. ReV. 2002, 31, 195.
(7) For reviews, see: (a) Kocienski, P. J. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol.
6 (Winterfeldt, E., Ed.), pp 975-1039. (b) Blakemore, P. R. J. Chem. Soc.,
Perkin Trans. 1 2002, 2563.
(8) For reviews, see: (a) Gro¨bel, B.-T.; Seebach, D. Synthesis 1977, 357.
(b) Page, P. C. B.; van Niel, M. B.; Prodger, J. C. Tetrahedron 1989, 45,
7643. (c) Yus, M.; Na´jera, C.; Foubelo, F. Tetrahedron 2003, 59, 6147.
(9) (a) Denis, J. N.; Dumont, W.; Krief, A. Tetrahedron Lett. 1979, 20,
4111. (b) Hoye, T. R.; Kurth, M. J. J. Org. Chem. 1980, 45, 3549. (c)
Shimagaki, M.; Shiokawa, M.; Sugai, K.; Teranaka, T.; Nakata, T.; Oishi,
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J.-C. Org. Lett. 1999, 1, 1539.
(10) For a review, see: Luh, T.-Y.; Ni, Z.-J. Synthesis 1990, 89.
10.1021/ol701579f CCC: $37.00
© 2007 American Chemical Society
Published on Web 08/03/2007

undergo ring-opening reactions selectively with an organo-
lithium or organocopper reagent to give the corresponding
sulfur-stabilized carbanions which can couple with a range
of electrophiles.13,14 When propargylic dithoacetals were
employed, the reactions have been applied for the synthesis
of substituted allenes,15 furans,16 and pyrroles.16a It is
envisaged that â-thioalkoxy alcohol may be conveniently
synthesized by this transformation when a carbonyl com-
pound is used as the electrophile.
Table 1. Olefination of Benzylic Dithioacetals 1
There has been an increasing use of iron catalysts for the
activation of C-X bonds in organic synthesis.17 Iron catalysts
are known to promote cross-coupling reactions of vinylic
thioethers and thioesters with Grignard reagents18 and
reduction of carbon-sulfur bonds.10,19 A σ-iron-alkyl might
be involved. We felt that a â-heteroatom elimination of such
σ-iron-alkyl intermediate might also take place leading to
the formation of olefin. In this paper, we report a new
olefination reaction of dithioacetals with carbonyl compounds
via the iron-promoted elimination of â-thioalkoxy alcohols.
Reactions of benzylic dithioacetal 1 with nBuLi followed
by carbonyl compounds afforded the corresponding â-thio-
alkoxy alcohols 2 in good yield. Treatment of 2 with 1 equiv
of Fe(acac)3 and 5 equiv of MeMgI in refluxing toluene for
40-48 h gave the corresponding olefins 3 in moderate to
good yield (eq 1).20 Representative examples are summarized
in Table 1.
% yield of 2
(dr ratio)
R1
R2
R3
R4
% yield of 3
a
b
c
d
e
f
Ph Ph
H
Me
Ph
H
H
H
H
H
79
90
61
87
63
82
72
84
75a
63
53
4-MeOC6H4
Ph Me PhCHdCH-
78 (3.0/1)
88
83b (2.0/1)
-C5H10
PhCHdCH
-
g
Ph
H
H
a E/Z ) 6/1. E isomer was obtained after recrystalization from ether-
pentane. bt BuLi was used.
We have previously shown that aryl-substituted propar-
gylic dithioacetals 4 react with nBuLi followed by treatment
with an aldehyde afforded regioselectively allenyl carbinols
5 which undergo cyclization upon treatment with trifluoro-
acetic acid to give corresponding trisubstituted furans 6 (eq
2).14,16
(11) Examples on stoichiometric â-heteroatom elimination reactions: (a)
Rosenblum, M. Pure Appl. Chem. 1984, 56, 129. (b) Daves, G. D., Jr. Acc.
Chem. Res. 1990, 23, 201.
(12) Examples on catalytic â-heteroatom elimination reactions: (a)
Henry, P. M. Acc. Chem. Res. 1973, 6, 16. (b) Karabelas, K.; Hallberg, A.
J. Org. Chem. 1986, 51, 5286. (c) Shi, X.; Luh, T.-Y. Organometallics
1990, 9, 3019. (d) Ma, S.; Lu, X. J. Chem. Soc., Chem. Commun. 1990,
733. (e) Sen, A.; Lin, M.; Kao, L.-C.; Huston, A. C. J. Am. Chem. Soc.
1992, 114, 6385. (f) Shiu, L.-L.; Yu, C.-C.; Wong, K.-T.; Chen, B.-L.;
Cheng, W.-L.; Yuan, T.-M.; Luh, T.-Y. Organometallics 1993, 12, 1018.
(g) Ma, S.; Lu, X. J. Org. Chem. 1991, 56, 5120. (h) Zhu, G.; Lu, X.
Organometallics 1995, 14, 4899.
(13) (a) Ikehara, H.; Tanimoto, S.; Oida, T. J. Chem. Soc., Perkin Trans.
1 1984, 1223. (b) Krief, A.; Kenda, B.; Barbeaux, P. Tetrahedron Lett.
1991, 32, 2509.
(14) For a recent review, see: Luh, T.-Y.; Lee, C.-F. Eur. J. Org. Chem.
2005, 3875.
Strikingly, when an alkyl-substituted propargylic dithio-
acetal 721 was employed, homopropargylic alcohol 8 was
obtained exclusively in good yield (eq 3). No allenylmethanol
derivatives like 5 were detected from the crude reaction
mixture. Typical results are summarized in Table 2. It is
worthy to mention that a range of carbonyl electrophiles can
be used in this coupling reaction. However, longer reaction
time (e.g., 8 h) was necessary for the reactions with a bulky
aldehyde (e.g., 8d). The discrepancy in selectivity of the
reaction with 4 and with 7 is unexpected.
(15) (a) Tseng, H.-R.; Luh, T.-Y. J. Org. Chem. 1996, 61, 8685. (b)
Tseng, H.-R.; Luh, T.-Y. J. Org. Chem. 1997, 62, 4568. (c) Tseng, H.-R.;
Lee, C.-F.; Yang, L.-M.; Luh, T.-Y. J. Org. Chem. 1999, 64, 8582.
(16) (a) Lee, C.-F.; Yang, L.-M.; Hwu, T.-Y.; Feng, A.-H.; Tseng, J.-
C.; Luh, T.-Y. J. Am. Chem. Soc. 2000, 122, 4992. (b) Zhang, L.-Z.; Chen,
C.-W.; Lee, C.-F.; Wu, C.-C.; Luh, T.-Y. Chem. Commun. 2002, 2336. (c)
Lee, C.-F.; Liu, C.-Y.; Song, H.-C.; Luo, S.-J.; Tseng, J.-C.; Tso, H.-H.;
Luh, T.-Y. Chem. Commun. 2002, 2824. (d) Liu, C.-Y.; Luh, T.-Y. Org.
Lett. 2002, 4, 4305. (e) Chou, C.-M.; Chen, W.-Q.; Chen, J.-H.; Tseng,
J.-C.; Lee, C.-F.; Luh, T.-Y. Chem. Asian J. 2006, 1-2, 46. (f) Tseng,
J.-C.; Chen, J.-H.; Luh, T.-Y. Synlett. 2006, 1209.
(17) (a) For a recent review, see: Fu¨rstner, A.; Martin, R. Chem. Lett.
2005, 34, 624. (b) Nakamura, M.; Matsuo, K.; Ito, S.; Nakamura, E. J. Am.
Chem. Soc. 2004, 126, 3686. (c) Nagano, T.; Hayashi, T. Org. Lett. 2004,
6, 1297. (d) Beford, R. B.; Bruce, D. W.; Frost, R. M.; Goodby, J. W.;
Hird, M. Chem. Commun. 2004, 2822. (e) Dunet, G.; Knochel, P. Synlett
2006, 407. (f) Dongol, K. G.; Koh, H.; Sau, M.; Chai, C. L. L. AdV. Synth.
Catal. 2007, 349, 1015.
Subsequent treatment of 8 with 1 equiv of Fe(acac)3 and
5 equiv of MeMgI afforded the corresponding enynes 9 in
(21) The aliphatic-substituted propargylic dithioacetals 7 were conve-
niently obtained from the alkylation of the anion of the corresponding parent
dithioacetals 10 (cf. Huang, L.-F.; Lee, C.-F.; Tseng, J.-C.; Luh, T.-Y. Synlett
2006, 3173). The details are described in the Supporting Information.
(18) (a) Cardellicchio, C.; Fiandanese, V.; Marchese, G.; Ronzini, L.
Tetrahedron Lett. 1985, 26, 3595. (b) Fiandanese, V.; Marchese, G.; Naso,
F. Tetrahedron Lett. 1988, 29, 3587. (c) Itami, K.; Higashi, S.; Mineno,
M.; Yoshida, J.-i. Org. Lett. 2005, 7, 1219.
(19) (a) Alper, H.; Prince, T. L. Angew. Chem., Int. Ed. 1980, 19, 315.
(b) Alper, H.; Ripley, S.; Prince, T. L. J. Org. Chem. 1983, 48, 250. (c)
Alper, H.; Sibtain, F.; Haveling, J. Tetrahedron Lett. 1985, 24, 5329.
(20) An excess amount of MeMgI (5 equiv) was necessary in order to
drive the reaction to completeness.
3664
Org. Lett., Vol. 9, No. 18, 2007

Table 2. Enynes 9 from Propargylic Dithioacetals 7
ing methylated products.23 As shown in Table 2, none of
methylated products were formed under these reaction
conditions. Although the actual mode of the iron-promoted
olefination is not clear at this stage, the benzylic or
propargylic carbon-sulfur bond may react preferentially with
low valent iron reagent. Elimination of the â-oxygen moiety
might then take place to give the corresponding olefin.
Presumably, this oxygen species might bond to iron and the
low valent iron cannot be regenerated under the reaction
conditions. Indeed, attempts to use subequivalent of Fe(acac)3
for this transformation gave low yield of product. The high
stereoselectivity in the olefination process might be attributed
to an equilibrated intermediate 14 (eq 6) which would lead
to a thermodymically more stable Z-olefin.
% yield of 8 % yield of
(dr ratio)
R1
R2
R3
R4
9 (Z/E)b
a
b
c
d
e
f
Cy
nBu
iPr
Ph
Me
H
H
Me
H
H
88a
79 (6.1/1)
89
73 (3.1/1)
84 (7.1/1)
81 (2.9/1)
81 (2.5/1)
73 (32/1)c
62 (22/1)
78
iPr
iPr
nBu nBu
nBu
TMS Ph
1-Ad
62d
74 (20/1)
63 (10/1)
77d
Ph
H
H
g
PhCHdCH
a Ratios are difficult to determine because of overlapping signals for
major and minor isomers. b Stereochemistry was assigned by NOE experi-
ments. c Products decomposed upon standing at rt. d A single diastereomer
was obtained.
good yield (Table 2). The reaction in general was stereose-
lective, Z-olefins being obtained as the major or the
predominant products when the secondary alcohols 8 were
employed. When propargylic ketone 11 was used, endiyne
9h was obtained in 52% yield (eq 4).
In summary, we have demonstrated a new olefination
reaction by coupling of a carbonyl compound with a
dithioacetal. A range of substituted alkenes and enynes can
be readily obtained by this protocol. The reaction can be
considered as an alternative of McMurry-type coupling of
two different carbonyl equivalents to give the corresponding
olefins. The in situ generated low valent iron reagent may
serve as a useful reagent for the activation of carbon-sulfur
bonds and for the elimiation of â-thioalkoxy alcohols.
Acknowledgment. We thank the National Science Coun-
cil and the National Taiwan University of the Republic of
China for financial support.
Supporting Information Available: Experimental details
for the synthesis of starting materials 7 and Fe(acac)3-
promoted olefination reactions. This material is available free
of charge via the Internet at http://pubs.acs.org.
Reaction of allylic dithioacetal 12 under the same condi-
tions afforded a mixture of diastereomers 13 (dr ) 5/1) (eq
5). Aliphatic substrates, however, underwent different kinds
of ring-opening processes to give a mixture of products.22
It is known that homopropargylic alcohols may react with
MeMgI in the presence of Fe(acac)3 to give the correspond-
OL701579F
(22) Wilson, S. R.; Georgiadis, G. M.; Khatri, H. N.; Bartmess, J. E. J.
Am. Chem. Soc. 1980, 102, 3577.
(23) Zhang, D.; Ready, J. M. J. Am. Chem. Soc. 2006, 128, 15050.
Org. Lett., Vol. 9, No. 18, 2007
3665