Reactions of transition-metal cyclopropyl and η1-allyl complexes with sulfur dioxide and disulfur monoxide

Article abstract of DOI:10.1021/om980590y

The preparations of several cyclopentadienyl iron dicarbonyl cyclopropyl and η¹-allyl complexes as well as (Me₂PhP)(CO)₄ manganese allyl complexes are reported. The iron complexes participated in 3 + 2 cycloaddition reacti

Full text of DOI:10.1021/om980590y

5534
Organometallics 1998, 17, 5534-5539
Rea ction s of Tr a n sition -Meta l Cyclop r op yl a n d η1-Allyl
Com p lexes w ith Su lfu r Dioxid e a n d Disu lfu r Mon oxid e
Brittany L. Hayes and Mark E. Welker*,†
Department of Chemistry, Wake Forest University, P.O. Box 7486, Winston-Salem,
North Carolina 27109
Received J uly 13, 1998
The preparations of several cyclopentadienyl iron dicarbonyl cyclopropyl and η1-allyl
complexes as well as (Me2PhP)(CO)4 manganese allyl complexes are reported. The iron
complexes participated in 3 + 2 cycloaddition reactions with sulfur dioxide (SO2) and disulfur
monoxide (S2O) to yield regioisomeric transition-metal substituted 1,2-oxathiolane 1-oxides
(sulfenate esters) and 1,2-dithiolane 1-oxides (thiosulfinate esters), respectively. The
manganese allyl complexes reacted with both SO2 and S2O to produce insertion products.
In tr od u ction
rations.6 In continuation of our efforts in this area, we
report here the preparation of cyclopentadienyl iron
dicarbonyl cyclopropyl and η1-allyl complexes and (Me2-
PhP)(CO)4 manganese η1-allyl complexes and their
reactions with SO2 and S2O. We note that five- and six-
membered-ring sulfur-containing heterocycles will pre-
sumably begin attracting increased attention as syn-
thetic targets because of a recent report that 1,2-
dithiolanes and 1,2-dithianes look particularly promising
as inhibitors of HIV type 1 replication.7 This replication
inhibition is apparently a result of their ability to attack
the conserved zinc fingers (presumably via the sulfur
of the heterocycle) of retroviral nucleocapsid proteins,
causing zinc ejection from the protein.
Cycloaddition reactions between transition-metal η1-
2-alkynyl (1) and η1-allyl complexes (1) and unsaturated
electrophilic reagents (2) have been studied in detail for
many years, and the pioneering work in this area was
done by the Rosenblum and Wojcicki groups.1 These 3
+ 2 cycloaddition reactions have been shown to yield
transition-metal-substituted five-membered-ring het-
erocycles and carbacycles (3) and offer alternative
approaches to these ring systems when the metal is
subsequently cleaved from the ring.1-3
Exp er im en ta l Section
Gen er a l. All nuclear magnetic resonances (NMR) were
obtained using a Varian VXR-200 FT NMR spectrometer. All
absorptions are expressed in parts per million relative to
residual undeuterated solvents. All infrared (IR) spectra were
obtained using a Perkin-Elmer 1620 FT-IR spectrophotometer.
All elemental analyses were performed by Atlantic Microlab
Inc. of Norcross, GA. High-resolution mass spectral analyses
(HRMS) were performed by the Nebraska Center for Mass
Spectrometry. Thin-layer chromatography was carried out on
0.20 mm precoated Polygram aluminum oxide plates or 0.25
mm precoated Polygram SIL G/UV silica plates. Routine
column chromatography was effected on alumina absorption
(150 mesh, neutral), purchased from Aldrich, or silica gel 60
purchased from VWR Scientific. Tetrahydrofuran was distilled
from sodium/benzophenone under nitrogen atmosphere im-
mediately prior to use. Toluene and pentane were distilled
from calcium hydride prior to use. All reactions were carried
out under an atmosphere of dry nitrogen unless otherwise
noted. Cyclopentadienyl iron dicarbonyl dimer, manganese
carbonyl dimer, and dimethylphenyl phosphine were pur-
Several years ago, we reported a variant of this 3 +
2 cycloaddition reaction which yields transition-metal-
substituted five-membered-ring thiosulfinate esters.1a,2
More recently, we have explored an example of this
reaction first reported by Wojcicki in 1977,4 involving
the cycloaddition of cyclopentadienyl iron dicarbonyl
2-alkynyl complexes with ketenes as a route to cyclo-
pentenones,5 and we have reported some new transition-
metal-mediated unsaturated cyclic sulfenate ester prepa-
† Henry Dreyfus Teacher-Scholar Awardee (1994-1999).
(1) For recent reviews of transition-metal mediated 3 + 2 cycload-
ditions see: (a) Welker, M. E. Chem. Rev. 1992, 92, 97. (b) Chan, D.
M. T. In Comprehensive Organic Syntheses; Trost, B. M., Ed.; Perga-
mon Press: New York, 1991; Vol. 5, p 271. (c) Wojcicki, A. Coord. Chem.
Rev. 1990, 105, 35. (d) Rosenblum, M. J . Organomet. Chem., 1986,
300, 191.
(2) (a) Fulcher, B. C.; Hunter, M. L.; Welker, M. E. Synth. Commun.
1993, 23, 217. (b) Raseta, M. E.; Mishra, R. K.; Cawood, S. A.; Welker,
M. E.; Rheingold, A. L. Organometallics 1991, 10, 2936. (c) Powell, K.
R.; Elias, W. J .; Welker, M. E. J . Organomet. Chem. 1991, 407, 81. (d)
Brown, D. S.; Owens, C. F.; Wilson, B. G.; Welker, M. E.; Rheingold,
A. L. Organometallics 1991, 10, 871. (e) Urove, G. A.; Welker, M. E.;
Eaton, B. E. J . Organomet. Chem. 1990, 384, 105. (f) Raseta, M. E.;
Cawood, S. A.; Welker, M. E.; Rheingold, A. L. J . Am. Chem. Soc. 1989,
111, 8268. (g) Urove, G. A.; Welker, M. E. Organometallics 1988, 7,
1013.
(5) Stokes, H. L.; Ni, L. M.; Belot, J . A.; Welker, M. E. J . Organomet.
Chem. 1995, 487, 95.
(6) Hurley, A. L.; Welker, M. E.; Day, C. S. Organometallics 1998,
17, 2832.
(3) The Turos and Baker groups have also made significant contri-
butions to this area of chemistry. For lead references see: (a) J iang,
S.; Chen, T.; Turos, E. Organometallics 1995, 14, 4710. (b) Abram, T.
S.; Baker, R.; Exon, C. M.; Rao, V. B.; Turner, R. W. J . Chem. Soc.,
Chem. Commun. 1984, 987.
(4) Chen, L. S.; Lichtenberg, D. W.; Robinson, P. W.; Yamamoto,
Y.; Wojcicki, A. Inorg. Chim Acta 1977, 25, 165.
(7) (a) Huang, M.; Maynard, A.; Turpin, J . A.; Graham, L.; J anini,
G. M.; Covell, D. G.; Rice, W. G. J . Med. Chem. 1998, 41, 1371. (b)
Rice, W. G.; Baker, D. C.; Schaeffer, C. A.; Graham, L.; Bu, M.;
Terpening, S.; Clanton, D.; Schultz, R.; Bader, J . P.; Buckheit, R. W.;
Field, L.; Singh, P. K.; Turpin, J . A. Antimicrob. Agents and Chemother.
1997, 41, 419. For a review see: Rice, W. G.; Turpin, J . A. Rev. Med.
Virology 1996, 6, 187.
10.1021/om980590y CCC: $15.00 © 1998 American Chemical Society
Publication on Web 11/11/1998

Transition-Metal Cyclopropyl and η1-Allyl Complexes
Organometallics, Vol. 17, No. 25, 1998 5535
chased from Strem Chemicals and used as received. Crotyl
chloride was purchased from Fluka and used as received.
Cyclopropyl bromide was purchased from Acros and used as
received. Magnesium bromide, trans-2-phenyl-1-cyclopropane
carbonyl chloride, methallyl chloride, and triethyl aluminum
were purchased from Aldrich and used as received. 4,5-
Diphenyl-3,6-dihydro-1,2-dithiin 1-oxide (17) was synthesized
according to a literature procedure.2a CpFe(CO)2CH2CHdCH2
(16),8 CpFe(CO)2CH2CHdCHCH3 (22),9 and (Me2PhP)Mn-
(CO)4CH2CHdCH2 (27a )10 were synthesized according to
literature procedures via addition of a THF solution of the
respective anion to a THF solution of the appropriate chloride.
3.01 (m, 1H), 2.61 (m, 2H); 12: 6.25 (dd, J ) 10.8, 4.4 Hz,
1H), 4.91 (s, 5H), 3.40 (m, 1H), 3.01 (m, 1H), 2.61 (m, 2H).
LRMS (FAB) (m/z): 283 (25) (M + H)+, 254 (9) (M+ - CO),
226 (100) (M+ - 2CO). Anal. Calcd For C10H10FeO4S: C, 42.58;
H, 3.57. Found: C, 42.67; H, 3.64. Acetonitrile, hexane, and
neat SO2 as solvents were also tried. Yields increased, but
diastereoselectivity was decreased (no reaction occurred in
hexane): acetonitrile (9, 0.175 g, 0.08 mmol yielded 11:12,
0.208 g, 0.07 mmol, 92%, 3:2), neat SO2 (9, 0.140 g, 0.64 mmol
yielded 11:12, 0.125 g, 0.44 mmol, 69%, 3:2).
Ba se/Lew is Acid Aid ed Syn th esis of 11 a n d 12. The
reaction was set up as described above. The Lewis acid (1.2
equiv) was added when the temperature of the iron complex
solution reached -78 °C. This was followed by the base (2.0
equiv) addition. Sulfur dioxide (10 mL) was condensed at -78
°C into the reaction mixture. It was allowed to stir at -78 °C
for 2 h and then warmed to 25 °C overnight. Saturated
aqueous NaHCO3 (50 mL) was added and extracted with ethyl
acetate (3 × 30 mL). The combined ethyl acetate extracts were
dried over MgSO4 and filtered, and solvent was removed by
rotary evaporation to produce a red-brown oil. The crude
product was purified by column chromatography on alumina
to yield diastereomers 11 and 12, identical by 1H NMR
comparison to the material reported above.
Cyclopen tadien yl(cyclopr opyl)dicar bon yl Ir on (9). This
compound has been previously reported with limited spectro-
scopic data.11 We have found the following prep to be superior
to both of the previously reported preparations of 9.11 Cyclo-
pentadienyl(cyclopropylcarbonyl)dicarbonyl iron (13, R ) H)
(0.5 g, 2.03 mmol) was synthesized according to literature
procedures.12 This complex was photolyzed at -78 °C using a
450 W low-pressure Hg Hanovia lamp in a Pyrex immersion
well for 1 h in toluene (200 mL). The reaction was monitored
by thin-layer chromatography (TLC) to ensure complete de-
carbonylation. The solvent was removed by rotary evaporation.
The product, a dark red-brown oil (9) (0.38 g, 1.70 mmol, 86%),
was used without further purification. IR (NaCl): 2005, 1945
cm-1. 1H NMR (C6D6): 3.99 (s, 5H), 0.77 (m, 2H), 0.50 (m, 1H),
0.25 (m, 2H). 13C NMR (C6D6): 217.27, 85.71, 8.81, -9.68.
HRMS (m/z): calcd for M+ (C10H10FeO2), 218.0030; found
218.0031. Anal. Calcd for C10H10FeO2: C, 55.09; H, 4.62.
Found: C, 54.87; H, 4.69.
a n ti- (18) an d syn -Cyclopen tadien yl(a n ti-4-(1,2-dith iol-
4-a n e 1-oxid e))d ica r bon yl Ir on (19). The η1-allyl iron
complex 16 (0.19 g, 0.87 mmol) was dissolved in tetrahydro-
furan (10 mL), and then 4,5-diphenyl-3,6-dihydro-1,2-dithiin
1-oxide (17) (0.31 g, 1.08 mmol) was added. The reaction
mixture was allowed to stir at 25 °C overnight and then
concentrated under reduced pressure. The crude product was
purified on a silica gel prep plate (diethyl ether, Rf ) 0.39)
yielding metallothiosulfinate ester (18) as a light yellow solid,
as a 8:1 mixture of anti (18) to syn (19) diastereomers (0.17 g,
0.53 mmol, 65% yield), mp 117-120 °C. IR (C6D6): 3234, 2014,
Cyclop en ta d ien yl(2-p h en yl-1-cyclop r op ylca r bon yl)d i-
ca r bon yl Ir on (13, R ) P h ). The iron dicarbonyl anion
[CpFe(CO)2-Na+] was generated by stirring a THF solution
of [CpFe(CO)2]2 (0.5 g, 1.4 mmol) over a 1% sodium amalgam
for 5 h. The anion was then added using a double-ended needle
to a THF solution of trans-2-phenyl-1-cyclopropanecarbonyl
chloride (2.0 equiv) cooled to -78 °C. This mixture was stirred
at -78 °C for 2 h and then allowed to warm to 25 °C overnight.
The solvent was removed by rotary evaporation, and the
remaining residue was dissolved in pentane and filtered
through Celite. The pentane was removed by rotary evapora-
tion to yield a red-brown oil (13, R ) Ph) (0.89 g, 2.76 mmol,
1956, 1618, 1456, 1450, 1391, 1337, 1325, 1162, 1074(SO) cm-1
.
1H NMR (anti, 18) (C6D6): 3.89 (s, 5H), 3.40 (m, 2H) 3.12 (m,
1H), 2.72 (dd, J ) 13.3 Hz, 9 Hz, 1H), 2.16 (dd, J ) 14 Hz,
11.2 Hz, 1H). HRMS EI calcd for C10H10O3S2Fe: 297.9421;
found 297.9421. Anal. Calcd for C10H10O3S2Fe: C, 40.28; H,
3.39. Found: C, 40.19; H, 3.41.
Cyclop en t a d ien yl(4-(1,2-d it h iol-4-a n e-5-m et h yl-1-ox-
id e))d ica r bon yl Ir on (23, 24, 25, 26). The iron allyl complex
(22) (0.048 g, 0.20 mmol) was dissolved in THF (15 mL) and
then treated with 4,5-diphenyl-3,6-dihydro-1,2-dithiin 1-oxide
(17) (1.24 equiv). The reaction mixture was allowed to stir for
55 h at 25 °C. The solvent was removed by rotary evaporation,
and the residue was purified by column chromatography on
alumina. Pentane removed any unreacted starting materials
and impurities, and elution with an ether gradient yielded an
8:3:1:1 ratio of diastereomers (23, 24, 25, 26) as a red-brown
oil (0.023 g, 0.074 mmol, 35%). IR (NaCl): 2960, 2917, 2853,
1999, 1949, 1066 cm-1. 1H NMR (CDCl3) (only diagnostic peaks
for each diastereomer are reported): 23 4.94 (s, 5H), 0.99 (d,
J ) 6.0 Hz, 3H); 24 4.89 (s, 5H), 1.73 (d, J ) 6.0 Hz, 3H); 25
4.86 (s, 5H), 1.61 (d, J ) 6.0 Hz, 3H); 26 4.82 (s, 5H), 1.49 (d,
J ) 6.0 Hz, 3H). LRMS (FAB): Calcd for C11H12FeO3S2Li
(M + Li)+ 319.1; found, 319.1.
Gen er a l P r oced u r e for th e Syn th esis of Ma n ga n ese
Allyl Com p lexes. The manganese carbonyl dimer [Mn2(CO)10]
(2.0 g, 5.13 mmol) was dissolved in toluene. Dimethylphenyl
phosphine (1.42 g, 10.3 mmol) was added to the reaction
mixture, which was degassed. The solution was refluxed for 6
h, and then the resulting orange solution was poured into
pentane (100 mL) and cooled to -78 °C. The yellow precipitate
[(Me2PhP)Mn(CO)4]2 was vacuum filtered and vacuum dried
(2.56 g, 4.2 mmol, 82%).13 The manganese anion was generated
by stirring a THF solution of [(Me2PhP)Mn(CO)4]2 over a 1%
sodium amalgam for 5 h. The anion was then added using a
98%). IR (NaCl): 2017, 1951, 1624 cm-1 1H NMR (C6D6):
.
7.09-6.89 (m, 5H), 4.13 (s, 5H), 2.78-2.60 (m, 2H), 1.83-1.74
(m, 1H), 1.04-0.95 (m, 1H). 13C NMR (C6D6): 249.45, 215.02,
141.47, 128.71, 128.32, 126.35, 86.15, 51.15, 28.61, 18.97. APT
(C6D6): 141.47 (C), 128.71 (CH), 128.32 (CH), 126.35 (CH),
86.15 (CH), 51.15 (CH), 28.61 (CH), 18.97 (CH2). Anal. Calcd
for C17H14FeO3: C, 63.35; H, 4.38. Found: C, 63.83; H, 4.63.
Cyclop en ta d ien yl(3-(1,2-oxa th iol-3-a n e-1-oxid e))d ica r -
bon yl Ir on (11, 12). The η1-cyclopropyl iron complex 9 (0.393
g, 1.8 mmol) was dissolved in toluene, purged with nitrogen,
and cooled to -78 °C. Sulfur dioxide (10 mL) was condensed
at -78 °C into the iron complex solution. It was allowed to
stir at -78 °C for 2 h and then warmed to 25 °C overnight.
The solvent was removed by rotary evaporation and high
vacuum. The crude product was purified by column chroma-
tography on alumina. Pentane removed any starting material
(9), and elution with an ether gradient yielded a 5:2 ratio of
the diastereomers as a red-brown oil (11:12) (0.169 g, 0.60
mmol, 33%). IR (NaCl): 2013, 1949, 1122, 1116, 1080 cm-1
.
1H NMR (CDCl3): 11: 5.45 (m, 1H), 4.89 (s, 5H), 3.40 (m, 1H),
(8) Bucheister, A.; Klemarczyk, P.; Rosenblum, M. Organometallics
1982, 1. 1679.
(9) (a) Green, M. L. H.; Nagy, P. L. I. J . Chem. Soc. 1963, 189. (b)
Downs, R. L.; Wojcicki, A. Inorg. Chim. Acta 1978, 27, 91.
(10) Palmer, G. T.; Basolo, F. J . Am. Chem. Soc., 1985, 107, 3122.
(11) Cutler, A.; Fish, R. W.; Giering, W. P.; Rosenblum, M. J . Am.
Chem. Soc. 1972, 94, 4354.
(12) Brookhart, M.; Studabaker, W. B.; Husk, G. R. Organometallics
1987, 6, 1141.
(13) Wawersik, H.; Basolo, F. Inorg. Chim. Acta 1969, 3, 113.

5536 Organometallics, Vol. 17, No. 25, 1998
Hayes and Welker
double-ended needle to a THF solution of the appropriate allyl
chloride (2.1 equiv) cooled to -78 °C. This mixture was stirred
at -78 °C for 2 h and then allowed to warm to 25 °C overnight.
The solvent was removed by rotary evaporation. The remain-
ing residue was dissolved in pentane (25 mL) and filtered
through Celite, and the flask was placed in a liquid nitrogen
bath. The yellow pentane solution was decanted away from
impurities. The pentane was removed by rotary evaporation
and high vacuum, and the allyl complexes (27a ,b) were used
immediately without any other further purification.
Te t r a ca r b on yl(2-m e t h yl-2-p r op e n yl)(d im e t h ylp h e -
n ylp h osp h in e)m a n ga n ese (27b). The manganese anion was
generated from [(Me2PhP)Mn(CO)4]2 (1.00 g, 1.60 mmol) and
then added to a THF solution of methallyl chloride (0.31 g,
3.44 mmol) using the procedure outlined above. The product
was obtained as an orange oil (27b) (1.085 g, 3.01 mmol, 77%).
IR (NaCl): 3060, 2912, 2044, 1957, 1955, 1607 cm-1. 1H NMR
(CDCl3): 7.50-7.39 (m, 5H), 4.50 (d, J ) 2.1 Hz, 1H), 4.23 (d,
J ) 2.1 Hz, 1H), 1.74 (d, J ) 8.3 Hz, 6H), 1.72 (s, 3H), 1.33 (d,
J (31P-1H) ) 7.4 Hz, 2H). 13C NMR (C3D6O): 206.08, 156.11
(d, J (31P-13C) ) 6.3 Hz), 138.00 (d, J (31P-13C) ) 40.5 Hz),
130.57 (d, J (31P-13C) ) 2.4 Hz), 130.02 (d, J (31P-13C) ) 8.8
Hz), 129.47 (d, J (31P-13C) ) 9.3 Hz), 102.32, 24.25, 17.78 (d,
J (31P-13C) ) 9.5 Hz), 15.95 (d, J (31P-13C) ) 28.7 Hz). APT
(C3D6O): 156.11 (C), 138.00 (C), 130.57 (CH), 130.02 (CH),
129.47 (CH), 103.22 (CH2), 24.25 (CH3), 17.78 (CH2), 15.95
(CH3). LRMS EI: calcd for C15H18MnO3P (M - CO)+ 332.0;
found, 332.1. LRMS FAB: calcd for C15H19MnO3P (M + H -
CO)+ 333.0; found, 333.0 (100), 305 (41) (M + H - 2CO)+, 277-
(27) (M + H - 3CO)+.
(28c) (0.042 g, 0.095 mmol, 36%). IR (NaCl): 2921, 2918, 2852,
1
1992, 1988, 1952, 1901, 1559, 1051, 942, 912 cm-1. H NMR
(CDCl3): 7.52-7.25 (m, 5H), 5.03 (s, 2H), 3.78 (q, J AB ) 12.8
Hz, 2H), 1.97-1.93 (m, 6H), 1.88 (s, 3H). LRMS FAB: calcd
for C16H18MnO5PS2Li (M + Li)+ 447.0; found, 446.3.
Resu lts a n d Discu ssion
We have been interested in the preparation of com-
pounds containing unusual organosulfur functional
groups because they have been identified as the biologi-
cally active components of many plants with traditional
medicinal applications. The -S-S(O)- (thiosulfinate
ester) functional group is present in a number of these
compounds, and thiosulfinate esters have been isolated
or synthesized which have biological activities as anti-
bacterials,14 antifungals14 (allicin (4), garlic), antivi-
rals,15 plant growth regulators16 (asparagusic acid S-
oxides (5), RdCO2H, asparagus; brugeriol and iso-
brugeriol (6), RdOH, mangroves), platelet aggregation
inhibitors17 (garlic), tumor growth inhibitors,18 and
anticarcinogenic enzyme inducers.19 This potential can-
(Me2P h P )(CO)4Mn (SO2-CH2CHdCH2) (28a ). The man-
ganese allyl complex (27a ) (0.185 g, 0.53 mmol) was dissolved
in THF, purged with nitrogen, and then cooled to -78 °C.
Sulfur dioxide (15 mL) was condensed at -78 °C into the
reaction mixture, which was allowed to stir at -78 °C for 2 h
and then warmed to 25 °C overnight. The solvent was removed
by rotary evaporation, and the remaining residue was vacuum
dried. Recrystallization from acetone/pentane afforded a bright
yellow solid (28a ) (0.210 g, 0.51 mmol, 96%), mp 87-90 °C.
cer chemopreventive activity has attracted increasing
attention over the past few years, and a variety of
organosulfur compounds (thiosulfinate esters and
dithiolthiones primarily) that are anticarcinogenic en-
zyme inducers (particularly glutathione S-transferase
inducers) have now been isolated or prepared.19 This
anticarcinogenic activity coupled with the recently
reported HIV-1 replication inhibition activity of 1,2-
dithiolanes7 forms the basis for our continuing interest
in the synthesis of five-membered-ring sulfur-containing
heterocycles.
IR (NaCl): 2099, 2082, 2012, 1953, 1037 cm-1 1H NMR
.
(C3D6O): 7.86-7.49 (m, 5H), 6.13-5.92 (m, 1H), 5.39 (d, J )
10.5 Hz, 1H), 5.38 (d, J ) 17.1 Hz, 1H), 3.60 (d, J ) 6.9 Hz,
2H), 2.21 (d, J ) 10.3 Hz, 6H). Anal. Calcd for C15H16O6-
MnPS: C, 43.92; H, 3.93. Found: C, 43.81; H, 4.02.
Reaction of CpFe(CO)2(cyclopropyl),11 CpFe(CO)2-
(allyl),20 and (PR3)(CO)4Mn(allyl)21 complexes with sul-
fur dioxide (SO2) has been reported previously, so most
of the current study deals with the reactions of these
complexes with disulfur monoxide (S2O). Initially, we
prepared the simplest CpFe(CO)2 cyclopropyl 9 by
reaction of CpFe(CO)2-Na+ (7) with cyclopropyl bro-
(Me2P h P )(CO)4Mn (S2O-CH2CHdCH2) (28b). The man-
ganese allyl complex 27a (0.122 g, 0.35 mmol) was dissolved
in THF. The 4,5-diphenyl-3,6-dihydro-1,2-dithiin 1-oxide (17)
(0.125 g, 0.44 mmol) was added, and the reaction mixture was
allowed to stir for 24 h. The solvent was removed by rotary
evaporation. The crude product was purified by column chro-
matography on silica. Pentane eluted the 2,3-diphenyl-1,3-
butadiene side product of S2O generation, and elution with
an ether gradient yielded an orange oil (28b) (0.095 g, 0.224
mmol, 64%). IR (NaCl): 3054, 2982, 2911, 2071, 1993, 1991,
(14) For a recent review on organosulfur compounds that have been
isolated from garlic, onions, and related plants and their biological
activities see: Block, E. Angew. Chem., Intl. Ed. Engl. 1992, 31, 1135-
78, and references therein.
(15) Frolov, A. F.; Mishenkova, E. L. Mikrobiol. Zh. Kiev 1970, 32,
628; Chem. Abstr. 1971, 74, 74916c.
(16) (a) Yanagawa, H.; Kato, T.; Kitahara, Y. Tetrahedron Lett. 1973,
1073. (b) Yanagawa, H.; Kato, T.; Kitahara, Y. Tetrahedron Lett. 1972,
2549. (c) Yanagawa, H.; Kato, T.; Sagami, H.; Kitahara, Y. Synthesis
1973, 607. (d) Yanagawa, H.; Kato, T.; Kitahara, Y. Tetrahedron Lett.
1973, 1073. (e) Kato, A.; Takahashi, J . Phytochemistry 1976, 15, 220.
(f) Kato, A.; Okutani, T. Tetrahedron Lett. 1972, 2959.
(17) Block, E.; Ahmad, S.; Catalfamo, J . L.; J ain, M. K.; Apitz-Castro,
R. J . Am. Chem. Soc. 1986, 108, 7045.
(18) (a) Hirsh, A. F.; Piantadosi, C.; Irvin, J . L. J . Med. Chem. 1965,
8, 10. (b) DePaulo, J . A.; Carruthers, C. Cancer Res. 1960, 20, 431.
(19) (a) Kohlmeier, L.; Su, S. R. FASEB J . 1997, 11, A369. (b)
Prochaska, J . J .; Santaria, A. B.; Talalay, P. Proc. Natl. Acad. Sci.
U.S.A. 1992, 89, 2394.
1
1950, 1617, 1045, 910 cm-1. H NMR (CDCl3): 7.56-7.38 (m,
5H), 6.02-5.90 (m, 1H), 5.33 (d, J ) 16.1 Hz, 1H), 5.35 (d, J
) 9.4 Hz, 1H), 3.79 (q, J AB ) 16.3 Hz, 2H), 1.93 (d, J ) 7.2 Hz,
3H), 1.89 (d, J ) 7.3 Hz, 3H). 13C NMR (C3D6O): 206.22, 137.31
(d, J (31P-13C) ) 43.8 Hz), 131.08 (d, J (31P-13C) ) 2.4 Hz),
130.29 (d, J (31P-13C) ) 9.0 Hz), 129.56 (d, J (31P-13C) ) 9.8
Hz), 125.98, 121.63, 67.84 (d, J (31P-13C) ) 10.7 Hz), 15.54 (d,
J (31P-13C) ) 7.8 Hz), 14.92 (d, J (31P-13C) ) 8.0 Hz). APT
(C3D6O): 137.31 (C), 131.08 (CH), 130.29 (CH), 129.56 (CH),
125.98 (CH), 121.63 (CH2), 67.84 (CH2), 15.54 (CH3), 14.92
(CH3). LRMS FAB: calcd for C15H16MnO5PS2 (M)+ 426.0;
found, 426.0.
(Me2P h P )(CO)4Mn (S2O-CH2C(Me)dCH2) (28c). The man-
ganese allyl complex 27b (0.087 g, 0.24 mmol) was dissolved
in THF. The 4,5-diphenyl-3,6-dihydro-1,2-dithiin 1-oxide (17)
(0.086 g, 0.30 mmol) was added, and the reaction mixture was
allowed to stir for 48 h. The reaction was worked up using
the procedure outlined above for 28b to yield an orange oil
(20) (a) Chen, L. S.; Su, S. R.; Wojcicki, A. J . Am. Chem. Soc. 1974,
96, 5655. (b) Chen, L. S.; Su, S. R.; Wojcicki, A. Inorg. Chim. Acta 1978,
27, 79.
(21) (a) Hartman, F. A.; Wojcicki, A. Inorg. Chim. Acta 1968, 2, 289.
(b) Hartman, F. A.; Wojcicki, A. Inorg. Chim. Acta 1968, 2, 351.

Transition-Metal Cyclopropyl and η1-Allyl Complexes
Organometallics, Vol. 17, No. 25, 1998 5537
mide11 and reaction of CpFe(CO)2Br with cyclopropyl-
lithium.11 However, isolated yields of 9 were always in
the 20-30% range, and we found reaction of CpFe-
(CO)2-Na+ (7) with cyclopropylcarbonyl chloride (8)
followed by decarbonylation to be a high-yield route to
9.22 Cyclopropyl complex 9 had been previously reported
to cyclize with SO2 to an unspecified diastereomeric
mixture of sultines (10),11 so we decided to first repeat
this reaction before moving on to more substituted
cyclopropyl complexes and S2O. We found that complex
9 reacted with SO2 in toluene at -78 °C to produce a
2.5:1 mixture of diastereomers in 33% yield. The isolated
yield of the 11/12 mixture improved to 69% in neat SO2;
however use of SO2 in the polar aprotic solvent aceto-
nitrile proved optimal, and we isolated the 11/12
mixture in 92% yield. Diastereoselectivity (11:12) was
decreased slightly to 1.5:1 by the solvent change. We
assigned the relative stereochemistry of the major (11)
and minor (12) diastereomers using the method of
Yanagawa, Kato, and Kitahara.16a,b They had reported
differences in the methine chemical shifts upon treat-
ment of methyl esters of natural products (5, R ) CO2-
Me) with Eu(FOD)3. We found that when the 11/12
mixture was treated with 0.4 equiv of Eu(FOD)3 (CDCl3),
the methine proton in the minor diastereomer (δ 6.25)
shifted downfield more than the major diastereomer (δ
5.45). On the basis of this chemical shift difference, we
propose the syn (11) and anti (12) relationships for the
major and minor diastereomers.
thwarted here by an inability to prepare the complexes.
Preparation of carbonylated cyclopropyls (13) proceeded
cleanly as before via reaction of the appropriate acid
chloride (R ) Me; R ) Ph) with CpFe(CO)2-Na+ (7).
23
The same photolysis conditions that worked well for the
decarbonylation to produce 9 resulted in rapid decom-
position of both of these substituted cyclopropyls (13).
Attempts to do modified Simmons-Smith type cyclo-
propanations24 on CpFe(CO)(vinyl) phosphine and phos-
phite complexes in hopes of producing more stable
cyclopropyls also were unsuccessful. Treatment of 9 with
our previously reported “S2O” source, 4,5-diphenyl-3,6-
dihydro-1,2-dithiin 1-oxide (17)2a in THF at 25 °C, also
resulted in decomposition of 9, so we turned our atten-
tion to the 3 + 2 cycloadditions of metal allyls with S2O.
Treatment of a variety of CpFe(CO)2(allyl) complexes
with SO2 has been reported previously by Wojcicki and
co-workers. Whereas the unsubstituted allyl (14, R )
R′ ) R′′ ) H) can provide a cyclized product upon rapid
removal of SO2, all other CpFe(CO)2 allyl complexes (14)
yielded insertion (15) rather than 3 + 2 cycloaddition
products when treated with SO2.20
In chemistry related to this, we have found that 16
reacts with S2O source 17 to yield 18 and 19 in 65%
yield as a 8:1 (18:19) mixture of diastereomers. The
assignment of relative positions of Fp (Fp ) CpFe(CO)2)
1
and O in 18 was based on H NMR coupling constants,
NOE experiments, and shift reagent experiments de-
scribed below. The metallothiosulfinate ester had a
characteristic SdO stretch in the IR at 1074 cm-1. The
1H NMR spectra (C6D6) of 18 and 19 showed the
expected double doublets for the protons of -CH2-
groups of the sulfur ring. Upon irradiation of a major
diastereomer one-proton multiplet at 3.12 ppm, all other
major peaks were simplified; therefore, this peak was
assigned to Hc of 18. Ha and Hd absorb around 3.4 ppm,
and Hb and He are below 3.0 ppm. Vicinal coupling
constants of 18 are analogous to those seen in the known
anti diastereomer of the methyl ester of asparagusic acid
S-oxide (5, R ) CO2Me): J ac ) 5.0 Hz, J bc ) 9.0 Hz, J dc
) 3.3 Hz, J ec ) 11.2 Hz.16
If proposed intermediate 10 is present, the diastereo-
selectivity of the ring closure might be influenced by
Lewis acid additives. However, knowing that these types
of iron complexes are also particularly sensitive to trace
protic acid, we decided to perform the SO2 cyclization
of 9 in the presence of Lewis acids and bases. We
performed these cyclizations in toluene and found that
while isolated yields of 11:12 improved with additives,
diastereoselectivity was little effected (MgBr2/NaHCO3,
11:12 1.5:1, 60%; MgBr2/Et3N, 11:12 2:1, 74%; Et3Al/
NaHCO3, 11:12 1:1, 62%).
We next wanted to look at this cycloaddition with
substituted cyclopropyl complexes; however, we were
(22) J ones et al. have previously reported this method as a good
route to related iron cyclopropyls: Trace, R. L.; J ones, W. M. J .
Organomet. Chem. 1989, 376, 103, and references therein.
(23) Conti, N. J .; Crowther, D. J .; Tivakornpannarai, S.; J ones, W.
M. Organometallics 1990, 9, 175.
(24) Ambler, P. W.; Davies, S. G. Tetrahedron Lett. 1988, 29, 6979.

5538 Organometallics, Vol. 17, No. 25, 1998
Hayes and Welker
Additional confirmation of relative stereochemistry 18
for the major diastereomer comes from shift reagent
experiments and NOE experiments. As mentioned
above, Yanagawa, Kato, and Kitahara had reported
differences in the methine (Hc) chemical shifts upon
treatment of methyl esters of natural products (5) with
Eu(FOD)3.16a,b When the 18/19 mixture was treated with
0.4 equiv of Eu(FOD)3, Hc in the major diastereomer
shifted downfield by an amount similar to that reported
previously for the natural product (5).16a,b Last, irradia-
tion of Ha and Hd produced a 4.4% NOE enhancement
of Hc. However, when He was irradiated, only a 0.9%
NOE enhancement was seen at Hc. Taken together,
these three pieces of evidence strongly implicate struc-
ture 18 for the major diastereomer.
product27 if the coordinating metal will bind with the
oxygen of sulfur and the oxygen of one of the carbonyls
on iron. When the divalent coordinating alkali metal
(MgBr2) was added to the reaction mixture, we observed
a 6:1 mixture of diastereomers of the product, anti (18):
syn (19), respectively. This observation of more syn
product is consistent with this coordination argument;
however, the syn diastereomer could not be formed
predominantly. Attempts to use other cations (SnCl2,
ZnCl2) resulted only in rapid decomposition of 17.
Cyclopentadienyl iron dicarbonyl crotonyl complex 22
(E:Z, 4:1) also reacts with 17 to produce thiosulfinate
ester products. This cyclization reaction now generates
three chiral centers so there are four possible diaster-
1
eomers. By H NMR, we saw four products (23, 24, 25,
26) in a 8:3:1:1 ratio. Once again, we determined the
stereochemistry using Eu(FOD)3 shift reagent experi-
ments and compared our results to the data reported
on the natural products, asparagusic acid S-oxides
(5),16a,b brugeriol, and isobrugeriol (6).16d,e We found that
when the 23/24/25/26 mixture was treated with 0.4
equiv of Eu(FOD)3, the methyl doublets of 23 and 24
moved downfield 2.9 ppm each, while this doublet only
shifted downfield by 2.2 ppm in 25 and 2.1 ppm in 26.
The Eu(FOD)3 shift reagent experiment results were
also used to determine the stereochemistry at the chiral
Formation of the anti diastereomer 18 can be ex-
plained via a mechanistic model analogous to ones
proposed by Rosenblum, Wojcicki, and us to explain
prior cyclizations with SO2 and S2O.1 The initial step
of this mechanism would involve nucleophilic attack by
the electrons of the CdC double bond from 16 on the
sulfoxide sulfur of 17. The conformation of 17 with the
sulfoxide oxygen in an axial position is about 3 kcal/
mol more stable than its equatorial counterpart.25
The compound 17 then undergoes electrocyclic ring
opening to generate cationic alkene iron intermediates
(20 and 21) and 2,3-diphenylbutadiene. Intramolecular
ring closure from 20 or 21 would then explain the
products. It is possible that this observed 18:19 ratio is
a kinetic result arising from approach of 16 toward the
least hindered face of the electrophilic sulfur in 17 as
depicted. However, 20 and 21 are potentially intercon-
vertible by a known thiosulfinate ester racemization
mechanism,26 so we cannot rule out the possibility that
this ratio is determined by ring closure rates of 20 and
21 regardless of which face of 17 reacts with 16.
1
center attached to the Fp group. The Cp singlet H NMR
resonances of 23 and 26 did not move downfield (0.65
ppm) as much as the analogous resonances of 24 and
25 (2.0 ppm). We can infer from these data that the E
isomer of 22 cyclized with a 8:1 (23:25) selectivity as
we saw for 16, whereas the Z isomer cyclized with a
reduced 3:1 selectivity (24:26).
Last, (PMe2Ph)(CO)4 manganese allyl complexes 27a
and 27b were also treated with SO2 for 27a and S2O
precursor 17 for 27a and 27b. The reaction of (CO)5Mn-
CH2-CHdCH2 with SO2 has previously been reported
to yield the SO2 insertion product analogous to 28a .21
We prepared 28a here so that its spectroscopic proper-
ties could be compared to those of 28b and 28c since
S2O insertion products have not been reported previ-
1
ously by our group. The alkenyl portion of the H NMR
of 28a is very similar to that of 27a , as expected.
However, the CH2 resonance of 28a (C3D6O, δ 3.60, d,
J
) 6.9 Hz) is easily distinguished from the CH2
resonance of 27a (C3D6O, δ 1.33, t, J 1H ) 31P ) 8.0
If a divalent coordinating metal is added to the
1
Hz) and is comparable to the H NMR CH2 resonance
reaction mixture, the syn (19) product could be the major
previously reported for (CO)5MnSO2CH2-CHdCH2
(CDCl3, δ 3.75, d, J ) 8 Hz).21a
(25) J uaristi, E.; Guzman, J .; Kane, V. V.; Glass, R. S. Tetrahedron
1984, 40, 1477.
(26) Mikolajczyk, M.; Drabowicz, J . Top. Stereochem. 1982, 13, 333.
(27) Ozin, G. A.; Gil, C. Chem. Rev. 1989, 89, 1749.

Transition-Metal Cyclopropyl and η1-Allyl Complexes
Organometallics, Vol. 17, No. 25, 1998 5539
Similarly, 27a and 27b reacted with S2O precursor
(17) to yield new complexes 28b and 28c with alkenyl
1H NMR resonances comparable to those seen in 27a
and 27b but with CH2 1H NMR resonances shifted
downfield to δ 3.79 and 3.78, respectively (CDCl3).
Unlike 28a , the central sulfur in complexes 28b and 28c
is a chiral center26 and the CH2 protons of both of these
complexes are diastereotopic (J AB ) 16 Hz in 28b, 13
Hz in 28c).
In conclusion, we have effected diastereoselective 3
+ 2 cycloaddition reactions of CpFe(CO)2 cyclopropyl
with SO2 and CpFe(CO)2 allyl complexes with S2O and
determined the relative stereochemistry of the major
diastereomers formed. In contrast, related phosphine
tetracarbonyl manganese allyl complexes reacted with
S2O to yield insertion rather than cycloaddition prod-
ucts. Biological screening data of sulfur heterocycles
generated by demetalation of these and related iron
complexes will be reported in due course.
Ack n ow led gm en t. We thank the NIH NIGMS and
the Camille and Henry Dreyfus Foundation (Henry
Dreyfus Teacher-Scholar Award to M.E.W., 1994-1999)
for their support. The Nebraska Center for Mass
Spectrometry (NSF DIR9017262) performed high-
resolution mass spectral analyses. We acknowledge
Rajesh Mishra for the initial preparation of complexes
18 and 19.
OM980590Y