Diastereoselective intramolecular pinacol couplings of sulfinyl iron(0) diene complexes

Article abstract of DOI:10.1021/jo802330x

3-(2-Fonnylaryl)-1-sulfinyl-(1Z, 3E)-pentadien-5-al iron tricarbonyl complexes were prepared to examine the feasibility and diastereoselectivity of intramolecular pinacol couplings on such substrates. It was found that the pinacol coupling, promoted by VC

Full text of DOI:10.1021/jo802330x

Diastereoselective Intramolecular Pinacol Couplings of Sulfinyl
Iron(0) Diene Complexes
Robert S. Paley,* Katherine E. Berry, Jane M. Liu, and Toby T. Sanan
Department of Chemistry and Biochemistry, Swarthmore College, 500 College AVe., Swarthmore,
PennsylVania 19081
rpaley1@swarthmore.edu
ReceiVed October 16, 2008
3-(2-Formylaryl)-1-sulfinyl-(1Z,3E)-pentadien-5-al iron tricarbonyl complexes were prepared to examine
the feasibility and diastereoselectivity of intramolecular pinacol couplings on such substrates. It was
found that the pinacol coupling, promoted by VCl3 · (THF)3/Zn, proceeded in good yield and with high
diastereoselectivity (>23:1 dr), provided the 2-formylaryl unit remained unsubstituted at the aryl C3
position (ortho to the formyl group). In these latter cases the pinacol coupling was diastereorandom. A
3-formyl-4-(2-formylaryl)-1-sulfinyl-(1Z,3E)-butadiene iron tricarbonyl complex also underwent diaste-
reoselective pinacol coupling (22:1 dr). 3-(3-Formylindolyl)-1-sulfinyl-(1Z,3E)-pentadien-5-al iron
tricarbonyl complexes were also prepared, though pinacol coupling of these substrates proceeded in, at
best, modest yield for two of the four examples tested. All cases described herein represent the first
intramolecular pinacol couplings performed on the periphery of an iron(0) diene tricarbonyl complex.
Introduction
exemplified by 3, can be prepared and diastereoselectively
transformed creating new stereocenters along the periphery of
the iron(0) diene complex.7 Spurred on by Uemura’s report8 of
diastereoselective intramolecular pinacol couplings of η6-arene
Cr(CO)3 complexes (Scheme 2), we chose to investigate if this
methodology could be successfully extended to appropriately
functionalized sulfinyl iron(0) diene complexes.
We were aware of only a single instance of an iron(0) diene
complex being used as the stereodirecting group in a pinacol
coupling: an intermolecular dimerization of an enantiopure
Diastereoselective transformations of the organic ligand of
transition metal complexes are among the fundamental meth-
odological tactics of modern synthesis. The most commonly
encountered examples involve manipulations of η6-arene Cr-
(CO)3 complexes,1 η4-diene Fe(CO)3 complexes,2 substituted
ferrocenes,3 and η3-allyl complexes.4 As a result of our interest
in developing new synthetic methods that utilize enantiomeri-
cally pure transition metal complexes with organic ligands, we
have previously described the diastereoselective complexation5
of enantiopure 1-(1Z)-sulfinyldienes, 1, that afford the corre-
sponding η4-diene Fe(CO)3 complexes, 2 (Scheme 1).6 Further-
more, we have reported that more functionalized complexes,
(2) (a) Kno¨lker, H.-J. In Transition Metals For Organic Synthesis; Beller,
M., Bolm, C., Eds.; Wiley-VCH: Weinheim, Germany, 2004; Vol. 1, pp. 585-
599. (b) Kno¨lker, H.-J.; Braier, A.; Bro¨cher, D. J.; Ca¨mmerer, S.; Fro¨hner, W.;
Gonser, P.; Hermann, H.; Herzberg, D.; Reddy, K. R.; Rohde, G. Pure Appl.
Chem. 2001, 73, 1075–1086. (c) Kno¨lker, H.-J. Chem. Soc. ReV. 1999, 28, 151–
157. (d) Donaldson, W. A. Curr. Org. Chem. 2000, 4, 837–868. (e) Gr´ee, R.;
Lellouche, J. P. In AdVances in Metal-Organic Chemistry; Liebeskind, L. S.,
Ed.; JAI Press: Greenwich, U.K., 1995; Vol. 4, pp. 129-273. (f) Donaldson,
W. A. In ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone,
F. G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford, U.K., 1995; Vol. 12,
pp. 623-635. (g) Pearson, A. J. In ComprehensiVe Organometallic Chemistry
II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford,
U.K., 1995; Vol. 12, p. 637. (h) Pearson, A. J. Iron Compounds in Organic
Synthesis; Academic Press: London, U.K., 1994.
* Corresponding author.
(1) (a) Rosillo, M.; Dom´ınguez, G.; Pe´rez-Castells, J. Chem. Soc. ReV. 2007,
36, 1589–1604. (b) Pape, A. R.; Kaliappan, K. P.; Ku¨ndig, E. P. Chem. ReV.
2000, 100, 2917–2940. (c) Rose-Munch, F.; Rose, E. Curr. Org. Chem. 1999,
3, 445–467. (d) Semmelhack, M. F. In ComprehensiVe Organometallic Chemistry
II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford,
U.K., 1995; Vol. 12, p. 979. (e) Davies, S. G.; McCarthy, T. D. In ComprehensiVe
Organometallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.;
Pergamon Press: Oxford, U.K., 1995; Vol. 12, p. 1039.
10.1021/jo802330x CCC: $40.75
Published on Web 01/13/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 1611–1620 1611

Paley et al.
SCHEME 1
SCHEME 3a
a Reagents and conditions: (a) 2M aq HCl/EtOAc (1:1). (b) SO3 ·pyr,
NEt3, DMSO/CH2Cl2 (1:1). (c) Hg(ClO4)2, CaCO3, THF/H2O (2:1). (d)
TBAF, THF. (e) PhI(O2CCF3), NaHCO3, CH3CN/H2O (85:15). See sup-
porting information for details.
SCHEME 2
couplings.12 For each complex the stereochemical assignment
for the position of the Fe(CO)3 fragment, relative to the sulfoxide
stereocenter, was made on the basis of the X-ray crystallographic
and 1H NMR spectroscopic precedence established for this class
of compounds.13 Conversion of complexes 4a-d into dialde-
hydes, 7a-d, via alcohols 5a-d and dithianyl aldehydes 6a-d,
was accomplished using straightforward functional group
manipulations (Scheme 3). Several details are noteworthy: First,
although complexes 4b-d were readily separated from their
corresponding minor ꢀ-facial diastereomers, the facial diaster-
eomers of complex 4a were inseparable. Rather than undertake
a tedious chromatographic separation of the diastereomers, this
mixture was carried through subsequent steps until the prepara-
tion of dialdehyde 7a, when the minor isomer was easily
removed. Second, the more sterically demanding η4-dienol
Fe(CO)3 complexes 5c and 5d, which possess axial chirality in
addition to planar chirality, showed some erosion of stereo-
chemical fidelity upon oxidation to the corresponding η4-dienal
Fe(CO)3 complexes 6c and 6d. Dithianyl aldehyde 6c was
obtained as a 9:1 diastereomeric mixture, and dithianyl aldehyde
6d was obtained as a ca. 30:1 mixture of diastereomers. We
have assigned these diastereomeric contaminants to be atropi-
somers, as a result of rotation about the aryl-iron(0) diene bond,
made possible by the reduced size of the allylic functionality
(formyl vs CH2OH). This process is minimized in 6d because
the dithiane unit is effectively larger due to the presence of the
ortho-methoxy group (which diminishes the dithiane’s confor-
mational mobility). Conversion of the diastereomeric mixture
iron(0) dienal complex proceeding through a ketyl-radical
intermediate.9 In fact, there appear to be only two other
examples in which any type of radical intermediate has been
generated along the diene periphery in η4-diene Fe(CO)3
complexes.10 Thus, as compared to the related η6-arene Cr(CO)3
complexes, where the chemistry of radicals formed at the
adjacent benzylic position is well studied and synthetically
useful,11 radical chemistry at allylic positions of η4-diene
Fe(CO)3 complexes remains quite underdeveloped. Herein, we
report the initial findings of our ongoing study.
Results and Discussion
Our prior communication described the synthesis of the
enantiopure sulfinyl iron(0) diene complexes, 4a-d, required
as precursors for the examination of the feasibility of the pinacol
(3) (a) Atkinson, R. C. J.; Gibson, V. C.; Long, N. J. Chem. Soc. ReV. 2004,
33, 313–328. (b) Sutcliffe, O. B.; Bryce, M. R. Tetrahedron: Asymmetry 2003,
14, 2297–2325. (c) Richards, C. J.; Locke, A. J. Tetrahedron: Asymmetry 1998,
9, 2377–2407. (d) Ferrocenes; Togni, A., Hayashi, T., Eds.; VCH: Weinheim,
Germany, 1995.
(4) (a) Garnier, E. C.; Liebeskind, L. S. J. Am. Chem. Soc. 2008, 130, 7449–
7458, and references therein. (b) Cox, L. R.; Ley, S. V. Chem. Soc. ReV. 1998,
27, 301–314. (c) Ley, S. V.; Cox, L. R.; Meek, G. Chem. ReV. 1996, 96, 423–
442.
(11) References 8, 9, and: (a) Byers, J. H.; Janson, N. J. Org. Lett. 2006, 8,
3453–3455. (b) Merlic, C. A.; Walsh, J. C. J. Org. Chem. 2001, 66, 2265–2274.
(c) Merlic, C. A.; Hietbrink, B. N.; Houk, K. N. J. Org. Chem. 2001, 66, 6738–
6744. (d) Merlic, C. A.; Miller, M. M.; Hietbrink, B. N.; Houk, K. N. J. Am.
Chem. Soc. 2001, 123, 4904–4918. (e) Merlic, C. A.; Walsh, J. C.; Tantillo,
D. J.; Houk, K. N. J. Am. Chem. Soc. 1999, 121, 3596–3606. (f) Schmalz, H.-
G.; de Koning, C. B.; Bernicke, D.; Siegel, S.; Pfletschinger, A. Angew. Chem.,
Int. Ed. Engl. 1999, 38, 1620–1623. (g) Merlic, C. A.; Walsh, J. C. Tetrahedron
Lett. 1998, 39, 2083–2086. (h) Taniguchi, N.; Uemura, M. Tetrahedron Lett.
1997, 38, 7199–7202. (i) Taniguchi, N.; Kaneta, N.; Uemura, M. J. Org. Chem.
1996, 61, 6088–6089. (j) Schmalz, H.-G.; Siegel, S.; Bats, J. W. Angew. Chem.,
Int. Ed. 1995, 34, 2383–2385. (k) Creary, X.; Mehrsheikh-Mohammadi, M. E.;
McDonald, S. J. Org. Chem. 1989, 54, 2904–2910.
(12) Paley, R. S.; Liu, J. M.; Lichtenstein, B. R.; Knoedler, V. L.; Sanan,
T. T.; Adams, D. J.; Fernandez, J.; Rablen, P. R. Org. Lett. 2003, 5, 309–312.
(13) 1H NMR: the chemical shift of the proton ꢀ to the sulfoxide was used
to assign the facial stereochemistry of the Fe(CO)3 fragment. See the Supporting
Information for ref 12. X-ray: (a) Paley, R. S.; Estroff, L. A.; McCulley, D. J.;
Mart´ınez-Cruz, L. A.; Jime´nez Sa´nchez, A.; Cano, F. H. Organometallics 1998,
17, 1841–1849. (b) Paley, R. S.; Rubio, M. B.; Ferna´ndez de la Pradilla, R.;
Dorado, R.; Hundal ne´e Sood, G.; Mart´ınez-Ripoll, M. Organometallics 1996,
15, 4672–4674.
(5) Paley, R. S. Chem. ReV. 2002, 102, 1493–1523.
(6) Paley, R. S.; de Dios, A.; Estroff, L. A.; Lafontaine, J. A.; Montero, C.;
McCulley, D. J.; Rubio, M. B.; Ventura, M. P.; Weers, H. L.; Ferna´ndez de la
Pradilla, R.; Castro, S.; Dorado, R.; Morente, M. J. Org. Chem. 1997, 62, 6326–
6343.
(7) Paley, R. S.; Estroff, L. A.; Gauguet, J.-M.; Hunt, D. K.; Newlin, R. C.
Org. Lett. 2000, 2, 365–368.
(8) Taniguchi, N.; Hata, T.; Uemura, M. Angew. Chem., Int. Ed. 1999, 9,
1232–1235.
(9) Taniguchi, N.; Uemura, M. Tetrahedron 1998, 54, 12775–12788.
(10) (a) Wei, L. L.; Lai, M. C.; Ong, C. W. Tetrahedron Lett. 2000, 41,
3407–3410. (b) Hwang, W.-S.; Liao, R.-L.; Ong, C. W. Polyhedron 1989, 8,
479.
1612 J. Org. Chem. Vol. 74, No. 4, 2009

Intramolecular Pinacol Couplings
TABLE 1. Intramolecular Pinacol Coupling of
3-(2-Formylaryl)-1-sulfinyl-(1Z,3E)-Pentadien-5-al Iron Tricarbonyl
Complexes, 7a-e
Though pinacol diacetates 9a-c were obtained with high
diastereoselectivity, conversion of dialdehyde 7d into diol 8d
exhibited a striking loss of diastereoselectivity. The reaction
proceeded in a diastereorandom manner. We assigned the trans
isomer of the corresponding diacetate (9d) to be the compound
with the JH5-H6 coupling constant of 2.7 Hz. This is in accord
with the assignments made by Lautens for dihydronaphthalenes
10d-g, which are compounds with a substituent ortho to the
benzylic alcohol (i.e., R1 * H).15 A similar coupling constant
of 3.5 Hz was also measured in a related dioxygenated
dihydrobenz[a]anthracene, as reported by Suzuki.17 Our assign-
ment is also supported by chemical shift data. In our series
(9a–e) the chemical shift of H6 is consistently 0.08-0.15 ppm
more downfield for the trans diastereomer (Table 2). To evaluate
whether the lack of selectivity in the pinacol coupling was due
to a bidentate coordination of the vanadium atom to the formyl
and ortho-methoxy substituents or to a steric effect, the related
substrate 7e was prepared from the known 6-iodo-3-methoxy-
2-methylbenzaldehyde (Scheme 4).18 Pinacol coupling of dial-
dehyde 7e was also diastereorandom, suggesting a steric origin
for the loss of selectivity, as well as a limitation of this
methodology. We attribute this to a destabilization of the
conformer (A, Figure 1) that would lead to the trans diastere-
omer. Equilibration to conformer B provides a pathway to the
cis isomer via the vanadium(III) ketyl. That two diastereomeric
diols are formed and not four suggests that the ketyl formed
adjacent to the iron(0) diene system is configurationally stable.
While it is possible that this configurational stability is a result
of an interaction between the ketyl p-orbital and the appropriate
d-orbital of the electron-rich iron atom, it is also likely that the
rotation about the C4-C5 bond is simply minimized as a result
of its steric environment. That is, it is expected that the s-trans
conformer of the aldehyde would be favored over the s-cis
conformer, and that this preference would be maintained during
the conversion to the corresponding ketyl. This is a situation
similar to one described by Merlic in a related η6-arene Cr(CO)3
complex,11b where it was concluded that steric effects play the
dominant role because of theoretical and experimental evidence
that the chromium tricarbonyl fragment does not significantly
stabilize adjacent radicals. It is possible that this argument also
pertains to radicals adjacent to iron(0) diene complexes with a
similar substitution pattern.
% yield, % yield,
dial
R1
R2
R3
R4
8a-e
9a-e
dr (trans/cis)a
7a
7b
7c
H
H
H
H
H
H
H
H
H
H
H
OMe
OMe
H
67
67
76
84
74
91
91
96
92
85
ca. 30:1
27:1
23:1
1:1.1
1:1.5
OMe
OMe
H
7d OMe
7e
Me
OMe
a
1
Determined by integration of the H NMR spectrum.
of 6c into dialdehyde 7c resulted in the formation of a single
compound, presumably because atropisomerism is no longer
possible. However, the more sterically demanding dialdehyde
7d was obtained as a 98.4:1.6 diastereomeric mixture. This
mixture was used in subsequent steps.
We were then delighted to discover that pinacol couplings
of dialdehydes 7a-c could be readily effected by treatment with
Pedersen’s reagent, [V2Cl3(THF)6]2(Zn2Cl6), prepared in situ by
treating VCl3 ·(THF)3 with Zn dust.14 Diols 8a-c were obtained
with excellent diastereoselectivities (Table 1: conversion of the
diols into the corresponding diacetates 9a-c facilitated 1H NMR
analysis). In the absence of our ability to crystallize any of
these compounds, we relied on a combination of precedence
1
and careful comparisons to H NMR spectroscopic data, of
related compounds, to assign the stereochemistry of the new
stereocenters of the pinacol products. By analogy to Uemura’s
example,8 as well as to many other known diastereoselective
conversions in iron(0) diene complex chemistry,2 the stereo-
chemistry of the C5 acetates was assigned as anti to the Fe(CO)3
fragment for each complex. The relative stereochemistry of the
major diastereomeric diacetates was assigned as trans, again
by analogy to the Uemura coupling, but also by the support of
That the Fe(CO)3 fragment can be removed to reveal the
1-sulfinyl diene unit without aromatization of the ring created
by the pinacol coupling was established by careful treatment
of diacetate 9b with CAN at low temperature to produce 19
(eq 1) as a 16:1 diastereomeric mixture.19
1
ample H NMR spectroscopic data of related compounds. For
example, the oxygenated dihydronaphthalenes 10a-c reported
by Lautens15 provide a useful comparison. The trans stereo-
chemistry of the substituents gave 1H NMR coupling constants
in the range of 10.3-11.0 Hz, which compares favorably to
the corresponding values of 10.7-11.2 Hz observed in the
spectra of the major diastereomers of 9a-c (Table 2). Addition-
ally, Suzuki reported broadening of the H5 and H6 signals at
ambient temperatures for the related dioxygenated dihydro-
phenanthrenes. We did not observe such broadening, but the
9a–c coupling constants are also consistent with those observed
by Suzuki at low temperature for conformers with substituents
in a trans diequatorial relationship (J ) 10.8 and 11.5 Hz).16
We have also endeavored to extend this methodology to
include indole systems, where we envisioned attaching a
(16) (a) Ohmori, K.; Kitamura, M.; Ishikawa, Y.; Kato, H.; Oorui, M.; Suzuki,
K. Tetrahedron Lett. 2002, 43, 7023–7026. (b) Ohmori, K.; Kitamura, M.; Suzuki,
K. Angew. Chem., Int. Ed. 1999, 38, 1226–1229.
(14) (a) Konradi, A. W.; Pedersen, S. F. J. Org. Chem. 1992, 57, 28–32. (b)
Freudenberger, J. H.; Konradi, A. W.; Pedersen, S. F. J. Am. Chem. Soc. 1989,
111, 8014–8016.
(15) Lautens, M.; Schmid, G. A.; Chau, A. J. Org. Chem. 2002, 67, 8043–
8053.
(17) Ohmori, K.; Mori, K.; Ishikawa, Y.; Tsuruta, H.; Kuwahara, S.; Harada,
N.; Suzuki, K. Angew. Chem., Int. Ed. 2004, 43, 3167–3171.
(18) Kende, A. S.; Curran, D. P. J. Am. Chem. Soc. 1979, 101, 1857–1864.
(19) Similar treatment of diol 8b produced the corresponding sulfinyl diene
in substantially poorer yield.
J. Org. Chem. Vol. 74, No. 4, 2009 1613

Paley et al.
TABLE 2. 1H NMR Data Including Comparison of Coupling Constants: Pinacol Diacetates (9a-e) vs Dihydronaphthalenes (Lautens,15
10a-g)
SCHEME 4
potential nucleophilic tether to the indole nitrogen for eventual
intramolecular attack on the corresponding decomplexed sulfinyl
diene or compounds derived from it. While this latter goal has
not yet been realized, we have prepared a series of pinacol
precursors and have examined the intramolecular pinacol
coupling of each of them. The synthesis of complexes 20a and
20b was previously reported.12 The conversion of each of these
to dialdehydes 23a and 23b is shown in Scheme 5. More
elaborate N-alkylated complexes 23c and 23d have also been
prepared. The synthetic routes to these compounds are depicted
in Schemes 6 and 7.
These reaction sequences feature a number of noteworthy
details. Indeed Schemes 6 and 7 feature the most highly
functionalized sulfinyl diene iron(0) tricarbonyl complexes that
we have prepared to date. First, it was necessary to assemble
the N-alkyl-2-alkynylindole 26 (Scheme 6) in the order pre-
sented. The Stille coupling (as well as the related Sonogashira
coupling) on the hindered N-alkyl-2-bromo-3-dithianylindole
FIGURE 1. Loss of diastereoselectivity during pinacol couplings.
1614 J. Org. Chem. Vol. 74, No. 4, 2009

Intramolecular Pinacol Couplings
SCHEME 5
a This yield represents the combined yield for the hydrolysis of the diastereomeric complexes, 20b. The diastereomeric alcohols were separable, and yield
of the depicted diastereomer, 21b, was 71%.
SCHEME 6
was not successful, and we were unable to prepare the N-alkyl-
2-bromo-3-formylindole from our 2-bromo-3-formylindole start-
ing material.20 Second, after selective deprotection of the TBS
ether to produce 27, Mitsunobu chemistry was used to install a
protected primary amine (the intended future intramolecular
nucleophile). For 28 (Scheme 6) the commercially available
N-BOC ethyl oxamate21 was employed, while synthesis of 38
(Scheme 7) featured the use of the previously unknown TEOC-
protected p-toluenesulfonamide 37.22 This later enabled the
sulfonamido nitrogen and the propargylic oxygen atoms to be
deprotected at the same time in order to produce 39 using
conditions which were compatible with the vinyl stannane
functionality. Third, the palladium-catalyzed hydrostannylation
(21) The Mitsunobu reaction of N-BOC ethyl oxamate has been de-
scribed: Berre´e, F.; Michelot, G.; Le Corre, M. Tetrahedron Lett. 1998, 39,
8275–8276.
(20) Gilchrist, T. L.; Kemmitt, P. D.; Germain, A. L. Tetrahedron 1997, 53,
4447–4456.
J. Org. Chem. Vol. 74, No. 4, 2009 1615

Paley et al.
SCHEME 7
SCHEME 8
of each of the 3-dithianyl-2-alkynylindoles proceeded with the
same high level of regioselectivity observed in the analogous
ortho-substituted benzene derivatives.23 Fourth, Stille coupling
of the atropisomeric (but racemic) vinyl stannane 32 (Scheme
6) gave the corresponding sulfinyl diene, 33, as a ca. 3.3:1
mixture of diastereomers (atropisomers). This appeared to be
an equilibrium mixture, since TLC showed that solutions of each
of the chromatographically separated atropisomeric sulfinyl
dienes become the same mixture upon standing. Stille coupling
with vinyl stannane 40 (Scheme 7) gave a similar (4:1)
atropisomeric mixture. Finally, complexation to provide the
corresponding sulfinyl iron(0) diene complexes proceeded with
a degree of dynamic kinetic resolution, as observed in related
systems.12 For the BOC-protected series (Scheme 6), evaluation
of the diastereomer ratio by 1H NMR integration was difficult.
At least three of the four possible diastereomers were observed,
and the analysis was further complicated by diastereomers
resulting from the presence of the stereocenter of the EE
protecting group. Our estimate is that the major diastereomer
of complex 34, which led to dialdehyde 23c, is formed in a ca.
5:1 ratio. Purification to a single diastereomer was carried out
following hydrolysis of the EE group. However, the H NMR
1
spectra of this series of complexes remained complicated,
possibly as a result of rotamers due to the BOC group. For the
Ts-protected series (Scheme 7), iron(0) diene complex 43 could
be purified to >95% purity after hydrolysis of the EE group.
The diastereomeric ratio of the complexation itself, which gave
42, was again difficult to evaluate. The major diastereomer
obtained after chromatography (a yield of 50% is cited in
Scheme 7) could not be rigorously purified from minor
1
diastereomers. However, after processing 42 into 23d, the H
NMR spectrum of the latter compound revealed only a trace of
a diastereomeric impurity.
Despite the significant effort put forth to prepare dialdehydes
23a-d, a reliable and high-yielding set of conditions for the
intramolecular pinacol coupling in this indole series has,
unfortunately, not yet been found (Scheme 8). For example,
the conversion of 23a into diol 45a using Pedersen’s method14
has, thus far, only been achieved in a modest 43% yield, though
it is reassuring to observe that a single diastereomer was
obtained in the process (assigned as trans, JH5-H6 ) 7.9 Hz, for
the corresponding diacetate). Unfortunately, substantial decom-
position occurred during the reaction, and unreacted dialdehyde
was neither observed or recovered. Similarly, diol 45c (trans,
JH5-H6 ) 8.0 Hz, for the corresponding diacetate) was obtained
(22) See the Supporting Information for the procedure for the synthesis
of 37.
(23) (a) Rubin, M.; Trofimov, A.; Gevorgyan, V. J. Am. Chem. Soc. 2005,
127, 10243–10249. (b) Alami, M.; Liron, F.; Gervais, M.; Peyrat, J. F.; Brion,
J. D. Angew. Chem., Int. Ed. 2002, 41, 1578–1580. (c) Liron, F.; Le Garrec, P.;
Alami, M. Synlett 1999, 246–248.
1616 J. Org. Chem. Vol. 74, No. 4, 2009

Intramolecular Pinacol Couplings
SCHEME 9
in a 23% yield using the method of Hirao.24 It remains unclear
if the ca. 5.5:1 ratio of peaks in the 1H NMR spectrum represents
a diastereomeric mixture or is a result of rotamers about the
N-BOC bond. We have been unable to prepare pinacol
coupling products from substrates 23b or 23d.
aryl-substituted sulfinyl dienes. Diene 14 (Scheme 4) could only
be prepared in modest yield because of a sluggish Stille
coupling. In this case, the high degree of substitution on the
aromatic ring presumably prevented the dithiane group from
adopting a conformation that would allow the beneficial
sulfur-palladium interaction to take place.
Finally, we examined the pinacol coupling of a substrate
where the positions of the aldehyde and the o-formyl aryl group
had been transposed. The preparation of the requisite dialdehyde
pinacol precursor also afforded us the opportunity to re-evaluate
the protecting group scheme used in the previously described
sequences. Our choice of the dithiane had not been arbitrary,
as we had been unable to carry out Stille couplings of aryl vinyl
stannanes possessing an ortho substituent unless a benzylic
sulfur atom was present.12 Presumably this was a result of a
favorable interaction between the palladium and sulfur atoms
that accelerated the key Stille transmetalation step.25 Unfortu-
nately, the use of the dithiane group also led to a reduced
diastereofacial selectivity in the Fe(CO)3 complexation step. We
believe this latter outcome was a result of heteroatom delivery5
of the Fe(CO)3 fragment from a dithiane sulfur atom that could
be positioned either above or below the diene plane. This would
bring the metal fragment toward the diene along competing
trajectories, somewhat removed from the directing influence of
the sulfoxide, and these trajectories likely possessed transition
states that were close in energy. With our intention to transpose
the groups along the diene periphery, it was logical to set aside
the dithiane protecting group in favor of an acetal. This group
would seem less likely to participate in the undesired heteroatom
delivery and would be strategically effective, if we could solve
the potential difficulties presented by a Stille coupling that would
no longer benefit from the sulfur-palladium interaction. Indeed,
we had already encountered a situation that pointed to the
challenges inherent in effecting the synthesis of this family of
With this challenge in mind, the diethyl acetal of o-iodoben-
zaldehyde was chosen as the starting point of the sequence. Negishi
coupling26 afforded the aryl alkynyl ester 46. Palladium-catalyzed
hydrostannylation of this substrate at room temperature resulted
in the formation of regioisomers in a 1:1 ratio, as the electronic
bias of hydride addition to the alkynyl ester27 could not
overcome the intrinsic regiochemical preference dictated by the
ortho substituent.23 The maximum yield of the desired regioi-
somer 47 was obtained by starting the hydrostannylation at
-78 °C and allowing the reaction mixture to warm to room
temperature slowly. A 1.7:1 ratio of regioisomers was obtained,
and the isomers were readily separated by chromatography.
After reduction and protection of the resulting alcohol, sulfinyl
diene 50 could be obtained in good yield by using the Stille
coupling conditions recently extolled by Fu¨rstner.28 Complex-
ation of this sulfinyl diene gave complex 51 with, as expected
an acetal rather than a dithiane, a high degree of diastereofacial
selectivity (>10:1). Routine functional group manipulation led
to the dialdehyde pinacol precursor 54, and the pinacol coupling
was successfully accomplished to produce diol 55 in a moderate
yield (49%), but with high diastereoselectivity (22:1). The trans
stereochemical assignment of corresponding diacetate (major
isomer: J ) 2.3 Hz; minor isomer: J ) 4.2 Hz) was based on
the precedence established by the analogous transformations
described above.
Conclusions
In conclusion, we have reported the first intramolecular
pinacol couplings performed on the periphery of an iron(0) diene
(24) Hirao, T.; Ogawa, A.; Asahara, M.; Muguruma, Y.; Sakurai, H. Org.
Syn. 2005, 81, 26–28. Diol 45c could not be prepared using Pedersen’s method. .
(25) (a) Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 36,
4704–4734. (b) Itami, K.; Kamei, T.; Yoshida, J. J. Am. Chem. Soc. 2001, 123,
8773–8779. (c) Crisp, G. T.; Gebauer, M. G. Tetrahedron Lett. 1995, 36, 3389–
3392. (d) Vedejs, E.; Haight, A. R.; Moss, W. O. J. Am. Chem. Soc. 1992, 114,
6556–6558.
(26) Anastasia, L.; Negishi, E. Org. Lett. 2001, 3, 3111–3113.
(27) Smith, N. D.; Mancuso, J.; Lautens, M. Chem. ReV. 2000, 100, 3257–
3282, and references therein.
(28) Fu¨rstner, A.; Funel, J.-A.; Tremblay, M.; Bouchez, L. C.; Nevado, C.;
Waser, M.; Ackerstaff, J.; Stimson, C. C. Chem. Commun. 2008, 2873–2875.
J. Org. Chem. Vol. 74, No. 4, 2009 1617

Paley et al.
1
evaporator. A H NMR spectrum of the crude material revealed a
1.7:1 ratio of regioisomers in favor of the desired vinyl stannane
47. The crude material was chromatographed (silica, 40:1 hexanes/
EtOAc with 1% NEt3) to give vinyl stannane 47 (374 mg, 61%) as
a clear oil. Fractions containing the minor isomer were pooled,
concentrated, and subjected to a second chromatography to afford
the regioisomeric vinyl stannne as a clear oil (185 mg, 30%). Data
for the major regioisomer (47): 1H NMR (400 MHz) δ 0.93 (t, 9H,
J ) 7.3 Hz), 1.09 (m, 6H), 1.24 (t, 6H, J ) 7.0 Hz), 1.39 (m, 6H),
1.58 (m, 6H), 3.52 (m, 2H), 3.56 (s, 3H), 3.64 (m, 2H), 5.55 (s,
1H), 7.22 (s with tin satellites, 1H, JSnH ) 24.6 Hz), 7.21-7.30
(m, 3H), 7.59 (d, 1H, J ) 8.1 Hz); 13C NMR (100 MHz) δ 10.6,
13.7, 15.2, 27.3, 28.9, 51.1, 61.6, 100.3, 126.3, 127.6, 128.1, 136.0,
137.0, 140.2, 143.2, 173.1; IR (neat) 2957, 2929, 2872, 1701, 1458,
1341, 1217, 1197, 1175, 1117, 1057, 760 cm-1. HRMS exact mass
calculated for [M + Na]+ 577.2310, found 577.2310. Data for the
tricarbonyl complex. The transformation is highly diastereose-
lective, but not without limitations, as substitution ortho to the
aromatic formyl group results in a complete loss of diastereo-
selectivity. Also, attempts to extend the methodology to indole
systems were only partially successful, as the pinacol coupling
proceeded in low to moderate yields in the best cases and failed
completely in others. The pinacol coupling precursors were the
most functionality-rich 1-sulfinyl diene iron(0) tricarbonyl
complexes we have prepared to date. As a consequence of
developing the synthetic routes to prepare them, a number of
other discoveries were made: (a) the importance of using the
Fu¨rstner modification of the Stille reaction for the preparation
of a hindered 1-sulfinyl diene, (b) the use of a new Mitsunobu
nucleophile (37), (c) the observation that 3-substituted 2-alky-
nylindoles undergo highly regioselective palladium-catalyzed
hydrostannylations, and (d) that it is possible to exert some
control over the regioselectivity of the hydrostannylation of an
alkyne (46) with conflicting regiochemically directing groups.
Furthermore, we gained useful insight about the atropisomeric
stability of 3-aryl-1-sulfinyl iron(0) tricarbonyl complexes 4-7.
We are continuing to explore other diastereoselective transfor-
mations of sulfinyl iron(0) diene complexes, as well as the
chemistry of the decomplexed sulfinyl dienes. These results will
be reported in due course.
1
minor regioisomer: H NMR (400 MHz) δ 0.88 (t, 9H, J ) 7.3
Hz), 0.92 (m, 6H), 1.14 (t, 6H, J ) 7.0 Hz), 1.2 (m, 6H), 1.43 (m,
6H), 3.35 (m, 1H), 3.48 (m, 2H), 3.52 (s, 3H), 3.70 (m, 1H), 5.29
(s, 1H), 6.22 (s with tin satellites, 1H, JSnH ) 28.0 Hz), 6.80 (m,
1H), 7.18 (m, 1H), 7.27 (m, 1H), 7.59 (dd, 1H, J ) 7.8, 1.2 Hz);
13C NMR (100 MHz) δ 10.4, 13.6, 15.0, 15.2, 27.3, 28.8, 50.9,
59.9, 62.2, 99.6, 123.7, 124.9, 126.2, 127.9, 128.6, 131.8, 143.9,
163.9, 169.5; IR (neat) 2957, 2928, 2872, 2854, 1732, 1713, 1464,
1351, 1263, 1192, 1161, 1053, 753 cm-1. HRMS (M + Na+)
calculated for C27H46O4NaSn 577.2310, found 577.2309.
Vinyl Stannane 48. Ester 47 (374.1 mg, 0.6761 mmol, 1 equiv)
was dissolved in toluene (6.8 mL) under an argon atmosphere, and
this solution was cooled to -78 °C. DIBAL (0.253 mL, 1.420
mmol, 2.1 equiv) was added via syringe. The solution was stirred
at -78 °C for 2 h, and the temperature was slowly raised to 0 °C
over 30 min. The reaction was quenched by addition of saturated
aq sodium potassium tartrate (6 mL). The mixture was vigorously
stirred for 15 min at room temperature, diluted with EtOAc (40
mL) and H2O (6 mL), and poured into a separatory funnel. The
organic layer was separated and the aqueous layer was extracted
with EtOAc (15 mL). The organic layers were combined, dried
(MgSO4), filtered, and concentrated on the rotary evaporator. The
residue was chromatographed (30:1 hexanes/EtOAc with 1% NEt3)
to afford alcohol 48 as a clear oil (299.3 mg, 84%). 1H NMR (400
MHz) δ 0.92 (t, 9H, J ) 7.3 Hz), 1.04 (m, 6H), 1.24 (t, 6H, J )
7.0 Hz), 1.39 (m, 6H), 1.61 (m, 6H), 1.80 (br t, 1H, J ) 5.0 Hz),
3.50-3.70 (m, 4H), 4.31 (br d with tin satellites, 2H, JHH ) 3.3
Hz, JSnH ) 20.8 Hz), 5.54 (s, 1H), 6.86 (t with tin satellites, 1H,
JHH ) 1.4 Hz, JSnH ) 34.0 Hz), 7.03 (m, 1H), 7.29 (m, 2H), 7.63
(m, 1H); 13C NMR (100 MHz) δ 10.3, 13.7, 15.2, 27.4, 29.3, 29.7,
61.7, 64.2, 100.1, 126.3, 126.8, 127.9, 129.1, 135.9, 136.6, 137.3,
151.1; IR (neat) 3485 (br), 2956, 2925, 1456, 1375, 1116, 1057,
762 cm-1. HRMS (M + Na+) calculated for C26H46O3NaSn
549.2361, found 549.2359.
Vinyl Stannane 49. Alcohol 48 (261.5 mg, 0.4978 mmol, 1
equiv) was dissolved in DMF under an inert argon atmosphere.
Imidazole (67.8 mg, 0.9955 mmol, 2.0 equiv), DMAP (12 mg, 0.100
mmol, 0.2 equiv), and TBSCl (93.8 mg, 0.622 mmol, 1.25 equiv)
were added consecutively. After 24 h the solution was diluted with
Et2O (100 mL) and saturated aq NaHCO3 solution (30 mL) and
this was transferred to a separatory funnel. The layers were
separated, and the aqueous layer was extracted with Et2O (30 mL).
The organic layers were combined and washed with brine (30 mL),
dried (MgSO4), filtered, and concentrated on the rotary evaporator.
The residue was purified by column chromatography (hexanes with
1% NEt3) to afford silyl ether 49 as a clear oil (306 mg, 96%). 1H
NMR (400 MHz) δ 0.01 (s, 6H), 0.87 (s, 9H), 0.93 (t, 9H, J ) 7.3
Hz), 0.99 (m, 6H), 1.24 (t, 6H, J ) 7.0 Hz), 1.38 (m, 6H), 1.58
(m, 6H), 3.51 (m, 2H), 3.66 (m, 2H), 4.40 (d with tin satellites,
2H, JHH ) 2.1 Hz, JSnH ) 18.2 Hz), 5.52 (s, 1H), 6.79 (t with tin
satellites, 1H, JHH ) 2.0 Hz, JSnH ) 35.3 Hz), 7.02 (m, 1H), 7.27
(m, 2H), 7.64 (m, 1H); 13C NMR (100 MHz) δ -5.3, 10.5, 13.8,
15.2, 18.5, 26.1, 27.5, 29.3, 62.2, 65.3, 100.2, 126.0, 126.8, 127.8,
Experimental Section
Representative Reaction Sequence for Preparation of Sulfi-
nyl Dienes, the Corresponding Iron(0) Diene Complexes, Pi-
nacol Coupling Precursors, and Products. Alkynyl Ester 46.
Diisopropylamine (0.259 mL, 1.85 mmol, 1.3 equiv) was dissolved
in THF (2 mL) in a flame-dried Schlenk flask under an argon
atmosphere. This solution was cooled to 0 °C, and n-BuLi (1.13
mL of a 1.6 M solution in hexanes, 1.81 mmol, 1.27 equiv) was
added via syringe. After stirring for 15 min, the solution was cooled
to -78 °C, and methyl propiolate (0.165 mL, 1.85 mmol, 1.3 equiv)
was added via syringe. After stirring 15 min, a freshly prepared
solution of ZnBr2 (417 mg, 1.85 mmol, 1.3 equiv) in THF (1 mL)
was added via cannula. After stirring an additional 15 min, a
solution of o-iodobenzaldehyde diethyl acetal (435.8 mg, 1.42
mmol, 1.0 equiv) in THF (1 mL) was added via cannula, followed
by Pd(PPh3)4 (82.3 mg, 0.0712 mmol, 0.05 equiv). The reaction
was stirred at -78 °C for 30 min, was warmed to 0 °C over 1 h,
was placed in a 45 °C oil bath, and was stirred at that temperature
for 20 h. After this time the solvent was removed on the rotary
evaporator, and the residue was dissolved in toluene (containing
3% NEt3 by volume) and was filtered through a bed of silica gel
on a glass frit filter using 4:1 hexanes/ethyl acetate (with 1% NEt3
by volume) as the eluant. The filtrate was concentrated on the rotary
evaporator to a brown oil that was chromatographed (silica gel,
19:1 hexanes/ethyl acetate with 1% NEt3) to afford aryl alkyne 46
as a clear oil (305.5 mg, 82%). 1H NMR (400 MHz) δ 1.28 (t, 6H,
J ) 7.1 Hz), 3.63 (m, 2H), 3.77 (m, 2H), 3.87 (s, 3H), 5.76 (s,
1H), 7.35 (td, 1H, J ) 7.6, 1.3 Hz), 7.50 (td, 1H, J ) 7.6, 1.1 Hz),
7.60 (dd, 1H, J ) 7.6, 1.2 Hz), 7.70 (dd, 1H, J ) 7.6, 1.2 Hz); 13
C
NMR (100 MHz) δ 15.2, 52.8, 63.2, 84.2, 84.5, 100.5, 118.3, 126.3,
128.4, 130.9, 133.7, 142.9, 154.4; IR (neat) 2978, 2881, 2223, 1715,
1435, 1299, 1207, 1176, 1061, 764 cm-1. HRMS (M + Na+)
calculated for C15H18O4Na 285.1097, found 285.1101.
Vinyl Stannane 47 (and Minor Regioisomer). Alkyne 46 (292.5
mg, 1.115 mmol) was dissolved in THF (11.2 mL) under an argon
atmosphere. Pd(PPh3)2Cl2 (23.5 mg, 0.0335 mmol, 3 mol%) was
added and the solution was cooled to -78 °C. Bu3SnH (0.600 mL,
2.23 mmol, 2 equiv) was added dropwise via syringe, and the
reaction was allowed to slowly warm to room temperature
overnight. At this time the solvent was removed on the rotary
1618 J. Org. Chem. Vol. 74, No. 4, 2009

Intramolecular Pinacol Couplings
128.9, 134.6, 136.2, 137.3, 152.2; IR (neat) 2956, 2928, 2856, 1464,
1252, 1117, 1055, 837, 779 cm-1. HRMS (M + Na+) calculated
for C32H60O3NaSiSn 663.3226, found 663.3239.
1H), 4.25 (s, 1H), 5.21 (d, 1H, J ) 7.3 Hz), 5.60 (s, 1H), 7.29-7.41
(m, 5H), 7.51 (d, 2H, J ) 8.2 Hz), 7.57 (dd, 1H, J ) 6.8, 2.0 Hz);
13C NMR (100 MHz) δ 15.0, 21.4, 62.3, 62.5, 63.7, 69.6, 74.4,
77.5, 102.1, 111.9, 123.3, 127.7, 127.8, 129.1, 130.0, 131.8, 134.2,
138.1, 140.9, 145.2; IR (CHCl3) 3342 (br), 2978, 2929, 2877, 2059,
1990, 1451, 1117, 1049, 811 cm-1. HRMS (M + Na+) calculated
for C26H28O7NaS56Fe 563.0797, found 563.0794.
Sulfinyl Diene 50. A Schlenk flask equipped with a stir bar was
charged with vinyl stannane 49 (302.1 mg, 0.4723 mmol, 1 equiv),
evacuated, and brought into the glovebox where it was dissolved
in anhydrous DMF (4.7 mL). The iodovinylsulfoxide6 (138 mg,
0.472 mmol, 1 equiv) was added to the stirred solution, followed
by CuTC (94.6 mg, 0.496 mmol, 1.05 equiv), Ph2PO2NBu4 (228
mg, 0.496 mmol, 1.05 equiv), and Pd(PPh3)4 (54.6 mg, 0.0472
mmol, 0.10 equiv). The flask was sealed, brought out of the
glovebox, and the contents were stirred at room temperature for
3 h. H2O (5 mL) was added, and the mixture was stirred for 15
min, when it was further diluted with Et2O (40 mL) and H2O (5
mL) and transferred to a separatory funnel. The layers were
separated, and the aqueous layer was extracted with Et2O (10 mL).
The organic layers were combined, dried (MgSO4), filtered, and
concentrated on the rotary evaporator to give a brown oil whichwas
placed on a vacuum pump overnight to remove DMF. The residue
was chromatographed twice (first, 3:1 hexanes/EtOAc; second, 4:1
to 3.5:1 hexanes/EtOAc) to afford sulfinyl diene 50 as a pale yellow-
Sulfinyl Dienal Iron(0) Tricarbonyl Complex 53. Alcohol 52
(93.0 mg, 0.172 mmol, 1 equiv) was dissolved in CH2Cl2 (0.67
mL) and DMSO (0.67 mL) under an argon atmosphere. NEt3 (0.24
mL, 1.72 mmol, 10 equiv) was added, followed by SO3 ·pyr (134
mg, 0.861 mmol, 5 eq), and this solution was stirred at room
temperature for 4.5 h. It was then diluted with EtOAc (35 mL),
washed with a 1M aq HCl solution (2 × 10 mL) and brine (2 × 10
mL), dried (MgSO4), filtered, and concentrated on the rotary
evaporator. The residue was purified by chromatography (5:1
hexanes/EtOAc with 1% NEt3) to afford aldehyde 53 as a yellow
1
oil (67.6 mg, 73%). H NMR (400 MHz) δ 1.17 (t, 3H, J ) 7.0
Hz), 1.24 (t, 3H, J ) 7.0 Hz), 2.43 (s, 3H), 3.46-3.76 (series of
multiplets, 4H), 3.67 (d, 1H, J ) 7.7 Hz), 4.44 (s, 1H), 5.50 (s,
1H), 5.68 (d, 1H, J ) 7.7 Hz), 7.32 (m, 3H), 7.39 (m, 2H), 7.51
(m, 3H), 9.65 (s, 1H); 13C NMR (100 MHz) δ 14.97, 15.02, 21.4,
62.5, 63.4, 67.8, 74.6, 79.6, 100.3, 103.4, 123.2, 127.95, 128.03,
128.9, 130.0, 132.4, 133.3, 138.4, 141.3, 145.1, 192.2, 207.3 (CO);
IR (CHCl3) 2977, 2874, 2064, 2007, 1709, 1053, 757 cm-1. HRMS
(M + Na+) calculated for C26H26O7NaS56Fe 561.0641, found
561.0625.
1
orange oil (163.5 mg, 67%). H NMR (400 MHz) δ 0.02 (s, 6H),
0.88 (s, 9H), 1.20 (overlapping triplets, 6H, J ) 7.0 Hz), 2.43 (s,
3H), 3.56 (m, 4H), 4.34 (one of AB system, 1H, J ) 11.7 Hz),
4.44 (one of AB system, 1H, J ) 11.7 Hz), 5.59 (s, 1H), 6.37 (d,
1H, J ) 10.5 Hz), 6.86 (dd, 1H, J ) 10.4, 1.2 Hz), 7.13 (s, 1H),
7.28-7.39 (m, 5H), 7.67 (m, 3H); 13C NMR (100 MHz) δ -5.3,
15.2, 18.3, 21.4, 25.9, 60.9, 61.4, 61.5, 99.7, 124.7, 126.6, 128.0,
129.7, 129.9, 134.7, 136.4, 137.3, 139.1, 141.0; IR (neat) 2955,
2929, 2883, 2857, 1471, 1254, 1082, 1046, 839, 777 cm-1. HRMS
(M + Na+) calculated for C29H42O4NaSSi 537.2465, found 537.2468.
Sulfinyl Diene Iron(0) Tricarbonyl Complex 51. (bda)Fe(CO)3
(450 mg, 1.573 mmol, 5 equiv) was added to a toluene (3.1 mL)
solution of sulfinyl diene 50 (162.0 mg, 0.3147 mmol) under an
Ar atmosphere. The flask was sealed and submerged in a 45 °C oil
bath. The reaction was stirred for 21 h, at which time the flask was
removed from the bath, and the contents were cooled to room
temperature. The solution was filtered through NEt3-treated silica
gel on a glass-fritted filter. The silica gel was washed with ample
EtOAc. The filtrate was evaporated, and the residue was chromato-
graphed (silica, 9:1 hexanes/EtOAc with 1% NEt3) to afford sulfinyl
iron complex 51 (131.8 mg, 64%) as a yellow oil and recovered
(bda)Fe(CO)3 (223 mg, 62% of the excess 4 equiv). 1H NMR (400
MHz) δ 0.04 (s, 3H), 0.06 (s, 3H), 0.91 (s, 9H), 1.24 (m, 6H),
2.44 (s, 3H), 3.48 (d, 1H, J ) 7.5 Hz), 3.51-3.62 (m, 3H), 3.71
(m, 1H), 4.07 (s, 1H), 4.13 (one of AB system, 1H, J ) 13.4 Hz),
4.62 (one of AB system, 1H, J ) 13.4 Hz), 5.27 (d, 1H, J ) 7.4
Hz), 5.63 (s, 1H), 7.33 (m, 5H), 7.52 (d, 2H, J ) 8.1 Hz), 7.63 (d,
1H, J ) 5.0 Hz); 13C NMR (100 MHz) δ -5.7, -5.5, 15.1, 15.2,
18.1, 21.4, 25.7, 61.2, 62.1, 62.3, 66.7, 72.8, 101.1, 114.5, 123.4,
127.3, 128.5, 129.9, 130.5, 135.1, 138.5, 140.7, 145.9; IR (neat)
2956, 2930, 2859, 2056, 1996, 1464, 1373, 1254, 1106, 1052, 839,
779 cm-1. HRMS (M + Na+) calculated for C32H42O7NaSSi56Fe
677.1662, found 677.1668.
Sulfinyl Dienal Iron(0) Tricarbonyl Complex (Pinacol Cou-
pling Precursor) 54. Acetal 53 (65.6 mg, 0.122 mmol) was
dissolved in EtOAc (1 mL). A 2 M aq solution of HCl (1 mL) was
added, and the reaction was stirred at room temperature for 4 h. At
this time it was diluted with EtOAc (30 mL) and transferred to a
separatory funnel, and the small aqueous layer was removed. The
organic layer was washed successively with a saturated aq NaHCO3
solution (2 × 7 mL) and brine (1 × 7 mL), was dried (MgSO4),
filtered, and concentrated on the rotary evaporator. The residue was
chromatographed (2:1 hexanes/EtOAc) to afford dialdehyde 54 as
an orange oil that solidified on the vacuum pump (45.7 mg, 81%).
1H NMR (400 MHz) δ 2.45 (s, 3H), 3.79 (d, 1H, J ) 7.8 Hz), 4.43
(s, 1H), 5.62 (dd, 1H, J ) 7.8, 0.8 Hz), 7.37 (d, 2H, J ) 8.3 Hz),
7.49 (d, 1H, J ) 7.5 Hz), 7.58 (d, 2H, J ) 8.3 Hz), 7.65 (m, 2H),
7.87 (dd, 1H, J ) 7.4, 1.6 Hz), 9.67 (s, 1H), 10.18 (d, 1H, J ) 0.3
Hz); 13C NMR (100 MHz) δ 21.5, 66.5, 80.8, 99.7, 123.3, 128.5,
130.2, 134.02, 134.05, 134.9, 135.6, 136.5, 141.4, 144.8, 191.3,
193.0, 206.9 (CO); IR (CHCl3) 3017, 2850, 2742, 2067, 2005, 1705,
1699, 1047 cm-1. HRMS (M + H+) calculated for C22H17O6S56Fe
465.0090, found 465.0085.
Pinacol Coupling Product (55) and Corresponding Diacetate.
In the glovebox, VCl3(THF)3 (56 mg, 0.151 mmol, 2.8 equiv) was
placed in a Schlenk flask. In the fumehood under an argon
atmosphere this was dissolved in CH2Cl2 (1.0 mL), and zinc dust
(6.2 mg, 0.094 mmol, 1.75 equiv) was added. The red solution
turned brown-green after ca. 5 min. The solution was stirred for a
total of 30 min, when it was cooled to 0 °C. A 0 °C CH2Cl2 (1.0
mL) solution of dialdehyde 54 (25 mg, 0.054 mmol, 1 equiv) was
added via cannula, and after 15 min the reaction was quenched
with 5% aq sodium tartrate solution (2 mL). This mixture was stirred
vigorously for 1 h, was diluted with CH2Cl2 (10 mL) and more 5%
aq sodium tartrate solution (10 mL), and was transferred to a
separatory funnel. The organic layer was separated, and the aqueous
layer was extracted with CH2Cl2 (1 × 10 mL). The combined
organic layers were dried (MgSO4), filtered, and concentrated. The
residue was chromatographed (silica, 1.5:1 to 1:1, hexanes/EtOAc)
to give diol 55 (12.3 mg, 49%) as a yellow oil that was fully
characterized as the corresponding diacetate. 1H NMR (400 MHz)
δ 2.40 (s, 3H), 3.49 (d, 1H, J ) 7.2 Hz), 4.21 (br m, 1H), 4.36 (s,
1H), 4.66 (br d, 1H, J ) 9.6 Hz), 4.94 (br d, 1H, J ) 8.9 Hz), 5.90
(d, 1H, J ) 7.1 Hz), 7.25-7.31 (m, 5H), 7.43 (d, 2H, J ) 8.1 Hz),
7.48 (d, 1H, J ) 7.6 Hz), 7.56 (d, 1H, J ) 5.9 Hz); 13C NMR (100
Sulfinyl Dienol Iron(0) Tricarbonyl Complex 52. Silyl ether
51 (115.6 mg, 0.177 mmol, 1 equiv) was dissolved in THF (1.8
mL). Acetic acid (14 µL, 0.25 mmol, 1.4 equiv) was added via
syringe, followed by a 1.0 M TBAF solution in THF (0.247 mL,
0.247 mmol, 1.4 equiv). After 70 min this solution was diluted
with EtOAc (40 mL), transferred to a separatory funnel, and washed
successively with saturated aq NaHCO3 (10 mL) and brine (10 mL).
After drying (MgSO4), filtration, and concentration of the organic
layer by rotary evaporation, the residue obtained was purified by
chromatography (4:1 hexanes/EtOAc with 1% NEt3 to 2:1 hexanes/
EtOAc with 1% NEt3) to afford alcohol 52 as a yellow oil (93.0
1
mg, 97%). H NMR (400 MHz) δ 1.26 (overlapping triplets, 6H,
J ) 7.0 Hz), 2.44 (s, 3H), 3.52 (d, 1H, J ) 7.3 Hz), 3.52-3.61 (m,
2H), 3.67-3.77 (m + broadened one of ABX system, 3H), 4.01
(broadened one of ABX system, 1H, J ) 11.6, 9.1 Hz), 4.22 (s,
J. Org. Chem. Vol. 74, No. 4, 2009 1619

Paley et al.
MHz) δ 21.4, 58.4, 73.6, 74.0, 74.5, 111.4, 123.4, 124.8, 127.4,
128.4, 128.7, 130.1, 135.2, 141.2, 144.2.
103.2, 123.1, 126.5, 128.0, 128.6, 128.8, 130.0, 130.1, 131.0, 136.7,
141.2, 144.8, 169.5, 169.8, 207.0 (CO); IR (CHCl3) 2995, 2926,
2062, 2000, 1743, 1492, 1370, 1217, 1047, 1024 cm-1. HRMS (M
+ H+) calculated for C26H23O8S56Fe 551.0458, found 551.0452.
The diol was dissolved in pyridine (0.3 mL). Acetic anhydride
(0.049 mL, 0.523 mmol, 20 equiv) and DMAP (1.6 mg, 13.1 µmol,
0.5 equiv) were added, and the solution was stirred overnight. The
reaction was diluted with EtOAc (20 mL), and this solution was
washed with 1 M aq HCl solution (2 × 5 mL), H2O (1 × 5 mL),
and brine (2 × 5 mL). After drying (MgSO4), filtration, and
concentration, the residue obtained was chromatographed (silica,
2:1 hexanes/EtOAc) to give the diacetate (12.4 mg, 86%) as a
yellow oil. The 1H NMR spectrum revealed a 22:1 diastereomeric
Acknowledgment. R.S.P. thanks the Dreyfus Foundation for
a Henry Dreyfus Teacher-Scholar Award (2000). This work was
also supported by Swarthmore College and HHMI.
Supporting Information Available: Full experimental pro-
cedures, spectra data, and copies of the 1H and 13C NMR spectra
for all new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
mixture. Major isomer: H NMR (400 MHz) δ 2.11 (s, 3H), 2.18
(s, 3H), 2.42 (s, 3H), 3.48 (d, 1H, J ) 7.3 Hz), 4.18 (s, 1H), 5.52
(dd, 1H, J ) 7.4, 1.0 Hz), 5.79 (d, 1H, J ) 2.3 Hz), 6.18 (d, 1H,
J ) 2.3 Hz), 7.28-7.40 (m, 7H), 7.46 (dd, 1H, J ) 7.1, 2.3 Hz);
13C NMR (100 MHz) δ 21.1, 21.4, 56.5, 69.3, 71.6, 74.3, 80.6,
JO802330X
1620 J. Org. Chem. Vol. 74, No. 4, 2009