Preparation of chiral-at-iron-substituted allyl and vinyl sulfones. Subsequent enolate generation and stereo-and regioselective alkylation

Article abstract of DOI:10.1021/om970448h

The (η⁵-cyclopentadienyl)Fe(CO)₂ (Fp) anion adds to allenic sulfone (CH2=C=CHSO₂Ph) to generate predominantly iron-substituted allyl or vinyl sulfones, depending on the reaction conditions chosen. Following a phosphine for CO ligand substitution, these allyl or vinyl sulfones can be deprotonated to yield carbanions, which can be alkylated regio- and stereoselectively. These alkylation reactions are unusual for allyl sulfones in that the ratio of α: γ alkylation changes dramatically as the electrophile structure changes.

Full text of DOI:10.1021/om970448h

Organometallics 1997, 16, 4519-4521
4519
P r ep a r a tion of Ch ir a l-a t-Ir on -Su bstitu ted Allyl a n d Vin yl
Su lfon es. Su bsequ en t En ola te Gen er a tion a n d Ster eo-
a n d Regioselective Alk yla tion
Paren P. Patel and Mark E. Welker*,†
Department of Chemistry, Wake Forest University, P.O. Box 7486,
Winston-Salem, North Carolina 27109
Louise M. Liable-Sands and Arnold L. Rheingold
Department of Chemistry, University of Delaware, Newark, Delaware 19716
Received May 30, 1997X
Summary: The (η5-cyclopentadienyl)Fe(CO)2 (Fp) anion
adds to allenic sulfone (CH2dCdCHSO2Ph) to generate
predominantly iron-substituted allyl or vinyl sulfones,
depending on the reaction conditions chosen. Following
a phosphine for CO ligand substitution, these allyl or
vinyl sulfones can be deprotonated to yield carbanions,
which can be alkylated regio- and stereoselectively.
These alkylation reactions are unusual for allyl sulfones
in that the ratio of R: γ alkylation changes dramatically
as the electrophile structure changes.
for CO substitution in solution lead only to the isolation
of η3-butadienyl complexes (4) rather than the desired
dienyl complex (5).
We have begun to pursue a strategy toward chiral-
at-iron-substituted dienes (5 and more highly substi-
tuted analogs thereof) that will ultimately rely on a
J ulia olefination.3 In this communication, we report the
preparation of chiral-at-iron-substituted allyl and vinyl
sulfones which will be required to pursue that strategy
as well as their subsequent deprotonation followed by
stereo- and regioselective alkylation.
Allenyl sulfones (9) have found widespread use in
organic synthesis as dienophiles and as diene precur-
sors.4 The central allene carbon in these sulfones is
highly electrophilic, and hence, they readily undergo
nucleophilic addition reactions. The simplest allenyl
phenylsulfone (9) is easily prepared from propargyl
chloride (6; Scheme 1).5 The Cp(CO)2Fe anion (1) was
added to 9 to generate the iron-substituted allylic and
vinyl sulfones (10 and 11) (35-45%).6 Isolated yields
of 10 and 11 are consistently in the 40% range for a
variety of reaction scales tried. We always recover a
For several years, we have been interested in explor-
ing how metal-centered chirality would affect the ster-
eochemical outcome of [4 + 2] cycloaddition reactions.1
In conjunction with these interests, we want to prepare
racemic then ultimately optically active chiral-at-iron
1,3-dienyl complexes (5). We have reported that the
CpFe(CO)2 anion (Fp anion)2 (1) reacted with allenic
electrophiles (2) in a SN2′ fashion to generate Fp-
substituted 1,3-dienyl complexes (3). Thermal and
(3) J ulia, M.; Paris, J .-M. Tetrahedron Lett. 1973, 14, 4833.
(4) Simpkins, N. S. Sulfones in Organic Synthesis; Pergamon:
Oxford, 1993; Chapter 2.
(5) (a) Herriott, A. W.; Picker, D. Synthesis 1975, 447. (b) Stirling,
C. J . M. J . Chem. Soc. C 1964, 5863. (c) Denmark, S. E.; Harmata, M.
A.; White, K. S. J . Org. Chem. 1987, 52, 4031.
(6) Cyclopentadienyliron dicarbonyl anion (1) was prepared from
[CpFe(CO)2]2 (0.600 g, 1.69 mmol) in THF (100 mL) using the method
of Piper and Wilkinson.2 Allenic sulfone (9) (0.72 g, 4.00 mmol) was
dissolved in THF (100 mL) and cooled to -78 °C. Iron anion (1) was
added to 9 slowly using a double-ended needle, and the mixture was
allowed to stir 2 h at -78 °C. The temperature was permitted to rise
to -20 °C over several hours and then quenched by the addition of
NH4Cl (aq) (25 mL) followed by water (100 mL). The aqueous was
extracted with EtOAc (3 × 100 mL), and the combined extracts were
dried (MgSO4). The solvent was removed by rotary evaporation, and
the product was chromatographed on alumina. Elution with hexane
yielded [CpFe(CO)2]2 (by TLC comparison to an authentic sample), and
elution with 9:1 hexane:EtOAc yielded 10:11 (1:3) (0.47 g, 1.31 mmol,
39%). Complexes 10 and 11 have surprisingly different solubility
characteristics, so this mixture of 10:11 could be triturated with 1:1
hexane:EtOAc to remove 10 and leave 11 behind as a yellow solid (350
mg). 1H NMR (C6D6): 8.11 (m, 2H), 6.99 (m, 3H), 6.82 (q, J ) 1.2 Hz,
1H), 3.79 (s, 5H), 2.66 (d, J ) 1.2 Hz, 3H). 13C NMR (C6D6): 214.94,
145.32, 135.08, 131.94, 129.11, 128.94, 127.17, 85.85, 34.01. IR (KBr):
2018, 1964, 1299, 1136, 1082 cm-1. Anal. Calcd for C16H14FeO4S: C,
53.65; H, 3.94. Found: C, 54.49; H, 4.31. LR FAB MS: 359 (25, M +
H+), 330 (15, M+ - CO), 302 (50, M+ - 2CO), 274 (25), 217 (100). HR
FAB MS calcd for C16H15FeO4S (M + H+): 359.0040. Found: 359.0050.
Complex 10 was also recovered as a yellow solid (100 mg) from the
liquid by adding hexane to induce precipitation. 1H NMR (C6D6): 7.70
(m, 2H), 6.96 (m, 3H), 6.03 (s, 1H), 5.47 (s, 1H), 4.40 (s, 5H), 3.87 (s,
2H). 13C NMR (C6D6): 216.56, 141.84, 139.32, 136.51, 132.82, 129.00,
photochemical attempts to do a phosphine or phosphite
* Author to whom correspondence should be addressed. E-mail:
welker@wfu.edu.
† Henry Dreyfus Teacher-Scholar Awardee (1994-99).
X Abstract published in Advance ACS Abstracts, September 15, 1997.
(1) (a) Smalley, T. L., J r.; Wright, M. W.; Garmon, S. A.; Welker,
M. E.; Rheingold, A. L. Organometallics 1993, 12, 998. (b) Stokes, H.
L.; Smalley, T. L.; Hunter, M. L.; Welker, M. E.; Rheingold, A. L. Inorg.
Chim. Acta 1994, 220, 305. (c) For an earlier report on iron dienyl
complexes prepared by a different route, see: Waterman, P. S.;
Belmonte, J . E.; Bauch, T. E.; Belmonte, P. A.; Giering, W. P. J .
Organomet. Chem. 1985, 294, 235.
128.20, 86.39, 74.53. IR (KBr): 2013, 1955, 1304, 1146, 1083 cm-1
.
Anal. Calcd for C16H14FeO4S: C, 53.65; H, 3.94. Found: C, 53.56; H,
4.00.
(2) Piper, T. S.; Wilkinson, G. J . Inorg. Nucl. Chem. 1956, 3, 104.
S0276-7333(97)00448-2 CCC: $14.00 © 1997 American Chemical Society

4520 Organometallics, Vol. 16, No. 21, 1997
Communications
Sch em e 1
significant amount of [CpFe(CO)2]2 dimer from these
reactions, so we suspect 9 reacts with 1 in redox and/or
acid-base chemistry to an appreciable extent. Isolated
yields of 10 and 11 based on recovered iron dimer [CpFe-
(CO)2]2 are in the 60-80% range. Iron-substituted allyl
sulfone (10) can be easily separated from the vinyl
sulfone (11) by hexane:ethyl acetate (1:1) trituration if
desired. The ratio of 11:10 increased as the tempera-
ture at which the reaction is quenched with water
increases (1:1.5 at -40 °C, 3:1 at -20 °C). The kinetic
product (10) also rearranged to 11 upon standing at 25
°C in CDCl3. The E stereochemistry of vinyl sulfone
(11) was proven by X-ray crystallography.7
Phosphine substitution on 10 to give 12 (80%), on 11
to give 13 (80%), or on the 10/11 mixture to produce 12
and 13 (80%) was easily achieved in toluene at 0 °C
using a 150 W flood lamp.8 The structure of the iron-
substituted allyl sulfone (12) has now also been con-
firmed by X-ray crystallography (Figure 1).9 In the solid
state, this complex (12) adopts a conformation where
the alkenyl CH2 (C(7), Figure 1) and the carbon mon-
oxide ligand are anti, analogous to the conformations
adopted by chiral-at-iron acyl complexes where the acyl
group oxygen and carbon monoxide ligands are anti.10
We have recently determined that the 12/13 mixture
(86%), pure 12 (90%), or pure 13 (86%) can be deproto-
F igu r e 1. ORTEP diagram with labeling scheme for
C33H29FeO3PS (12). Selected bond distances (Å) and angles
(deg): Fe-C(6) 1.725(5), Fe-C(8) 1.995(4), Fe-P 2.2065-
(14), C(7)-C(8) 1.328(5), C(8)-C(9) 1.523(5); C(6)-Fe-C(8)
96.0(2), C(8)-Fe-P 92.52(12), C(6)-Fe-P 89.20(14), C(7)-
C(8)-C(9) 119.8(4), C(7)-C(8)-Fe 126.0(3).
nated with BuLi followed by treatment with MeI to
produce a product (14a ) where alkylation has occurred
R to the sulfone with high diastereoselectivity (12.5:1).11
Since 12 adopts a solid state conformation like the
analogous acyl complexes10 and they alkylate anti to the
PPh3 ligand, we would anticipate that 12 would react
to produce the diastereomer shown (14a ). This observed
diastereoselectivity is apparently a kinetic ratio since
the anion of 12 was generated and quenched with MeI
at -78 °C, and we find that this diastereoselectivity does
(7) Complete details of the X-ray crystallographic characterization
of 11 are provided in the Supporting Information. Crystallographic data
for 11: monoclinic, P21, Z ) 2, a ) 9.831(3) Å, b ) 8.009(2) Å, c )
11.212(2) Å, â ) 115.03(2)°, V ) 799.9(4) Å3, Dcalc ) 1.487 g/cm3; Mo
KR radiation (λ ) 0.710 73 Å); 1745 independent reflections with 2.00
< θ < 25.01 collected, R ) 0.0500, Rw ) 0.1313, GOF ) 1.327.
(8) Stokes, H. L.; Ni, L. M.; Belot, J . A.; Welker, M. E. J . Organomet.
Chem. 1995, 487, 95 and references therein. Iron complex (11) (0.300
g, 0.84 mmol) and PPh3 (0.264 g, 1.01 mmol) were dissolved in
deoxygenated toluene (20mL) and photolyzed at 0 °C under N2 for 24
h using a 150 W flood lamp. During this photolysis, the solution color
changes from yellow to red-orange. The solvent was removed by rotary
evaporation. The crude product was triturated with 9:1 hexane:EtOAc
to remove excess PPh3 and provided 13 as a red-orange solid (398 mg,
0.67 mmol, 80%). 1H NMR (C6D6): 7.92 (m, 2H), 7.25-6.99 (m, 18H),
6.50 (s, 1H), 4.03 (d, J ) 1.2 Hz, 5H), 2.88 (t, J ) 1.4 Hz, 3H). 13C
NMR (CDCl3): 220.3 (d, J ) 33 Hz), 144.3, 135.0 (d, J ) 42 Hz), 132.9,
131.5, 130.7, 130.6, 130.1, 128.5, 128.2, 126.9, 85.8, 34.5. IR (KBr):
1925, 1431, 1296, 1255, 1132, 1079 cm-1. LR FAB MS: 593 (17, M +
H+), 564 (40, M+ - CO). HR FAB MS calcd for C33H30FeO3PS (M +
H+): 593.1003. Found: 593.1016.
(9) Complete details of the X-ray crystallographic characterization
of 12 are provided in the Supporting Information. Crystallographic data
for 12: monoclinic, P21/c, Z ) 4, a ) 11.120(4) Å, b ) 16.613(4) Å, c )
15.994(3) Å, â ) 107.00(3)°, V ) 2825.6(11) Å3, Dcalc ) 1.393 g/cm3; Mo
KR radiation (λ ) 0.710 73 Å); 3683 independent reflections with 2.27
< θ < 22.49 collected, R ) 0.0418, Rw ) 0.0805, GOF ) 0.864. Some
sulfoxide-containing chiral-at-iron acyls have been reported previously,
but to our knowledge these chiral at iron alkenyl sulfones are unknown,
see: (a) Davies, S. G.; Gravatt, G. L. J . Chem. Soc., Chem. Commun.
1988, 780. (b) Baker, R. W.; Davies, S. G. Tetrahedron: Asymmetry
1993, 4, 1479. Chiral-at-iron sulfonyl complexes (analogous to the acyls)
have also been reported, see: Flood, T. C.; DiSanti, F. J .; Miles, D. L.
Inorg. Chem. 1976, 15, 1910.
(10) For a review of conformational analysis of the CpFe(CO)(PPh3)
auxiliary, see: Blackburn, B. K.; Davies, S. G.; Whittaker, M. In
Stereochemistry of Organometallic Inorganic Compounds 3; Bernal, I.,
Ed.; Elsevier, Amsterdam, 1989; pp 141-223.

Communications
Organometallics, Vol. 16, No. 21, 1997 4521
deteriorate some when 14a is subsequently treated with
1N NaOH in C6D6 at 25 °C (5:1 after 6 h). Interestingly,
the enolate of 12/13 also alkylated diastereoselectively
with EtI, but the regioselectivity begins to deteriorate.
The regiochemistry of the alkylation continues to change
when PrI is used and switches to a preference for γ
alkylation by the time unsaturated alkyl halides are
used as the alkylating agents. Allyl bromide reacted
to produce a preponderance of the γ-alkylated product
(15d ), and benzyl bromide alkylated to produce only the
preference for alkylation at the softer nucleophilc γ
carbon13 or possibly the switch to bromides as alkylating
agents for d and e had an effect on the rates of
alkylation at the R and γ sites.
In summary, we have demonstrated that CpFe(CO)2
anions can add to allenic sulfones to generate predomi-
nantly iron-susbsituted allyl or vinyl sulfones, depend-
ing on the reaction conditions chosen. These allyl or
vinyl sulfones can be deprotonated to yield carbanions,
which can be alkylated regio- and stereoselectively. The
regiochemistry of these alkylations is unusual in that
γ alkylation increases as the size of the alkylating
electrophile increases. Successful generation and alky-
lation of sulfone-stabilized allylic carbanions in the
presence of transition-metal complexes should now
allow organometallic chemists to explore J ulia olefina-
tions as a new method for synthesizing transition-metal
dienyl complexes. We will report our efforts along those
lines in due course.
1
γ product (15e), as observed by H NMR. This change
in electrophile alkylation site with change in electrophile
structure is very unusual for allylic sulfone anions which
alkylate almost exclusively R rather than γ to the
sulfone regardless of substrate used.12 This change in
regiochemistry of alkylation is presumably predomi-
nantly a steric effect and is due to the presence of both
the bulky CpFe(CO)PPh3 fragment and the SO2Ph
group. However, part of the change in regiochemistry
of alkylation may arise from the fact that the softer
allylic and benzylic electrophiles have an electronic
Ack n ow led gm en t. We thank the Donors of the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, and the Camille and Henry
Dreyfus Foundation (Henry Dreyfus Teacher-Scholar
Award to M.E.W., 1994-99) for their support. Low-
resolution mass spectra were obtained on an instrument
purchased with the partial support of NSF (Grant No.
CHE-9007366). The Nebraska Center for Mass Spec-
trometry (Grant No. NSF DIR9017262) performed the
high-resolution mass spectral analyses.
(11) Generation and alkylation of the enolate of CpFe(CO)-
(PPh3)COCH2SCH3 has also been reported, see: Wisniewski, K.;
Pakulski, Z.; Zamojski, A.; Sheldrick, W. S. J . Organomet. Chem. 1996,
523, 1. A representative example of our alkylation procedure follows.
Iron allyl sulfone (12) (0.050 g, 0.084 mmol) was dissolved in THF (5
mL) and cooled to -78 °C. BuLi (40 µL of a 1.7 M solution in hexanes,
0.105 mmol) was added dropwise, and the orange solution changed to
a deep amber color. The anion was allowed to stir 15 min at -78 °C,
then CH3I (0.023 g, 0.17 mmol) was added. The solution was allowed
to stir for 2 h at -78 °C then warmed to 25 °C, and during this time,
the deep amber anion color changed back to the original orange color.
Saturated NaCl (5 mL) was added, and the aqueous layer was
extracted with EtOAc (3 × 5 mL). The organic extracts were dried (Na2-
SO4), and the solvent was removed by rotary evaporation. The product
was recrystallized from hexane/EtOAc to yield 14a as a red solid (0.045
g, 0.074 mmol, 88%). 1H NMR (C6D6): 8.12 (m, 2H), 7.55 (m, 6H), 7.02
(m, 12H), 6.58 (s, 1H), 5.62 (s, 1H), 4.55 (s, 5H), 4.36 (q, J ) 7.0 Hz,
Su p p or tin g In for m a tion Ava ila ble: Tables giving de-
tails of the X-ray structure determinations, atomic coordinates
and isotropic thermal parameters, bond lengths and bond
angles, and anisotropic displacement parameters for 11 and
12, an ORTEP diagram of 11, and experimental details of the
preparation and characterization of 10-15 (19 pages). Order-
ing information is given on any current masthead page.
1H), 1.18 (d, J ) 7.0 Hz, 3H). IR (KBr): 1909, 1433, 1298, 1142 cm-1
.
LR FAB MS: 607 (7, M + H+), 578 (22, M+ - CO), 459 (23), 411 (36),
383 (100). HR FAB MS calcd for C34H32FeO3PS (M + H+): 607.1135.
Found: 607.1128.
(12) (a) Reference 4, pp 111-118. (b) Savoia, D.; Trombini, C.;
Umani-Ronchi, A. J . Chem. Soc., Perkin Trans. 1 1977, 123. (c)
J onczyk, A.; Radwan-Pytlewski, T. J . Org. Chem. 1983, 48, 910. (d)
Hayakawa, K.; Nishiyama, H.; Kanematsu, K. J . Org. Chem. 1985,
50, 512. (e) Trost, B. M.; Schmuff, N. R. J . Am. Chem. Soc. 1985, 107,
396.
OM970448H
(13) Pearson, R. G.; Songstad, J . J . Am. Chem. Soc. 1967, 89, 1827.