2502
J. Org. Chem. 1995,60, 2502-2505
High Yield Synthesis of Monosubstituted Ferrocenes Denis Guillaneux and Henri B. Kagan* Laboratoire de Synthbse Asymbtrique, URA CNRS no. 1497,Znstitut de Chimie Molbulaire &Orsay, 91405 Orsay, France Received November 16, 1994@
The direct lithiation of ferrocene using a n alkyllithium was widely explored and improved, but monolithioferrocene was never obtained fully devoid of 1,l'-dilithioferrocene. Pure (tri-n-butylstannyllferrocene was isolated in good yield from ferrocene (through the above lithiation). It can be stored and used (a) as an excellent precursor of pure monolithioferrocene,leading through reaction with many electrophiles to monosubstituted ferrocenes in nearly quantitative yields; (b) as a nucleophile in Stille cross-couplings with good results; (c) a s a precursor of halogenoferrocenes through tin-halogen exchange. Many synthetic methods for the introduction of the ferrocenyl moiety in a wide range of molecular structures have been described in the These methods are efficient since they allow the preparation of monosubstituted and 1,l'-disubstituted products selectively. However, the preparation of the precursors in the synthesis of monosubstituted ferrocenes is tedious and yields are not reproducible. Some procedures for the direct monolithiation of ferrocene have been de~cribed,7-~ one of the best ones (giving up to 70% of monosubstituted product) having been set up in our l a b ~ r a t o r y .Mueller-Westerhoff ~ et aLaaalso proposed a synthesis of ferrocenecarboxaldehyde through an improved monolithiation of ferrocene.8b We found that our previous method of monolithiation of ferrocene,' although convenient for the preparation of various monosubstituted ferrocenes after quenching by many electrophiles, gave unsatisfactory results in some cases. For example, (R)-p-tolylferrocenyl sulfoxide prepared by the Andersen methodlo had a specific rotation of - 4 (c = 0.9, CHC13, 1% and the same product prepared via a modified procedure (excess of menthyl p-tolylsulfinate) had a specific rotation of - 257 (c = 0.46, CHCls, 82%ee).l1 Some racemization of the sulfoxide was catalyzed by traces of strong bases (excess tBuLi or l-(p tolylsulfinyl)-1'-lithioferrocene formed in situ) a s established in other cases.12 Therefore, we looked for a preparation of pure monolithioferrocene. @Abstractpublished in Advance ACS Abstracts, March 15, 1995. (1)For the use of chloromercurioferrocenes, see ref 2. (2)Seyferth, D.;Hofmann, H. P.; Burton, R.; Helling, J. F. I n o g . Chem. 1962,1,227-231.Reeve, W.; Group, E. F., Jr. J . Org. Chem. 1967,32,122-125. (3)For the use of halogenoferrocenes, see Popp, F. D.; Moynahan, E. B. J. Org. Chem. 1969,34,454-456.Hedberg, F.L.;Rosenberg, H. Tetrnhedron Lett. 1969,46,4011-4012.Rausch, M. D.;Moser, G. A,; Meade, C. F. J. Organomet. Chem. 1973,51,1-11. (4)For the use of boronoferrocenes, see Nesmejanow, A. N.; Ssasonowa, W. A.; Drosd, V. N. Chem. Ber. 1960,93,2717-2729. (5)For the use of 1,l'-dilithioferrocene TMEDA adduct, see Bishop, J. J.; Davison, A.; Katcher, M. L.; Lichtenberg, D. W.; Merrill, R. E.; Smart, J . C. J . Organomet. Chem. 1971,27,241-249. (6) For the use of 1,l'-bis(tri-n-butylstannyl)ferrocene, see Wright, M. E. Organometallics 1990,9,853-856. (7)Rebigre, F.; Samuel, 0.;Kagan, H. E. Tetrahedron Lett. 1990, 31,3121-3124. (8) (a) Mueller-Westerhoff, U.T.; Yang, 2.;Ingram, G. J . Organomet. Chem. 1993,463,163-167. (b) Our attempts in reproducing experiments of ref 8a were unsuccessful. (9) For a review on the metalation of metallocenes, see Slocum, D. W.; Engelmann, T. R.; Ernst, C.; Jennings, C. A.; Jones, W.; Koonsvitsky, B.; Lewis, J.; Shenkin, P. J. Chem. Ed. 1969,46,144-150. (lO)Andersen, K. K. J . Org. Chem. 1964,29,1953-1956. (11)Rebigre, F.; Riant, 0.;Ricard, L.; Kagan, H. E. Angew. Chem. Int. Ed. Engl. 1993,32,568-570.
-Scheme 1
Fe
GP 1
RLI
solvent temperature
Fe
+
2a
1
a Fe 1
e ' *L'' Fe Fe
1
+
-LI
3a ~ B U ~ S ~ C I
e S n " B u 3 -Sn"Bug +
Fe 2b
+
Fe -snn~u3 3b
Direct Metalation of Ferrocene. We studied the effects of the different parameters influencing the direct lithiation of ferrocene 1 (Scheme 1). First, we tested the commercially available lithium bases in various solvents, we studied the conditions of the metalation step and finally we investigated the effect of the RLYl ratio. Since the direct measurement of the 112d3a ratio is not easy, we had to find a n indirect method for evaluating this ratio. Wright showed that "BusSnCl readily reacts with the TMEDA adduct of 1,l'-dilithioferrocene to give 1,l'-bis(tri-n-butylstanny1)ferrocene(3b)in good yields,6 and the 'H NMR peaks of the ferrocenyl protons of 1, 2b, and 3b are separated enough for a n accurate measurement of the 1/2b/3b ratio (see Experimental Section). So we quenched mixtures of lithiated ferrocenes with the very reactive "Bu3SnC1and assumed for our study that the observed ratio 1/2b/3b corresponds to the ratio 1/2d 3a formed during the lithiation reaction. Two different types of product distribution may be of great interest: (a) maximum yield of 2b; and (b) maximum selectivity of the monolithiation (highest 2b/3b ratio), even in low yield, since 1 is generally easy to remove from the product through chromatography or sublimation. Thus, we selected two parameters in order to compare our experiments: the conversion of 1 and the 2bf3b ratio. Influence of Solvent and MetalatingAgent. Table 1 presents the best results obtained using equimolar amounts of ferrocene and lithium bases and a slight excess of electrophile in various solvents. We also performed metalations according to the procedures of Rebihre et al.' and Mueller-Westerhoff et daa as a comparison. LDA and MeLi failed for the deprotonation of ferrocene in any solvent. ~~~~~
(12)Furukawa, N.; Ogawa, S.; Matsumara, K.; Fujihara, H. J . Org. Chem. 1991,56,6341-6348.
0022-3263/95/1960-2502$09.00/00 1995 American Chemical Society
High Yield Synthesis of Monosubstituted Ferrocenes Table 1. Influence of Solvent and Metalating Agenta baseb LDAorMeLi nBuLi
solventC ef
OEtze THFg sBuLi THF/OEt@ tBuLi OEW THFhexaneh THFIOEtZh THFh method of ref 7' method of ref Sd
1/2b/3bd 100/0/0 84/12f4 7811616 591347 81/12/7 33/60/7 26/63/11 40/47/13 45/41/11 41/39/20
2bl3b
3.0 2.7 4.9 1.7 8.6 5.7 3.6 4.0 2.0
Experiments on a 10 mmol scale. The metalating agent was added during a n approximately 10 min period to 1 a t 0 "C, and reactions were quenched after 1 h of stirring at 0 "C with nBu3SnC1 at 0 "C and allowed to stand for 1 h at rt. Reactant ratio was FcHJRLiPBwSnCl: 1/1/1.1. Volumes: OEtz 40 mL, THFhexane 5 mU5 mL, THF/OEtZ 5 mU5 mL, THF 10 mL. Determined by 'H NMR of the crude product. e Metalation overnight. f N o evidence of substituted products in OEtz, THFIOEtz, or THF. 8 Metalation over 3 h. Metalation over l h. l lPBuLiPBu3SnCl : 1.5/ 1.311, THF 10 mL, addition of tBuLi at 0 "C and metalation over 15 min at 0 "C. J lPBuLiPBu3SnCl 1/1.5/2, THF 30 mL, addition of tBuLi a t -20 "C over 15 min, stirring during 30 min and warming to -10 "C before quenching.
Most of the direct metalations of ferrocene classically described in the literature were performed with "BuLi in ethers (OEt2, THF),g using excess "BuLi over long periods of metalation and giving only moderate yields. Our own experiments using 1 equiv of "BuLi with respect to ferrocene also gave low conversions of 1 and low 2b/ 3b ratios. The reaction needs long periods of metalation, which is a problem if we consider the stability of lithium species in ethers. Previous studies showed that alkyllithium compounds have short lifetimes in ethers (tBuLi has half-lives of only 40 min in THF at -20 "C and of 1 h in OEt2 a t 0 "C),13 and we ourselves (vide infra) established that 2a decomposes quite rapidly a t temperatures above -40 "C when THF is used as a part of the solvent . "uLi is more selective than "BuLi in the monolithiation (giving a good 2bl3b ratio), but the conversion of 1 remains low. The use of tBuLi gave far better conversions of 1, but some 3b was always present. tBuLi in THFhexane or THF10Et2 improve conversions and product ratios compared to THF alone (even according to the procedures of refs 7 and Ba), so we restricted our study to the metalations using tBuLi in THFhexane, THFlOEt2 and THF. Conditions of the Metalation.14 Lithiations of ferrocene were performed using tBuLi in the above conditions over various times and t e m ~ e 7 a t u r e s . l ~Some general trends emerge from that study. First of all, yields and 2bl3b ratios were always higher in THFI hexane or THFIOEt2 than in THF. This could be due to differences between the solubilities of lithioferrocenes in those solvents. During the addition of tBuLi, the brown, partly insoluble 1 present in all experiments (except in THF a t room temperature) disappeared while precipitation of lithioferrocenes occurred (orange red in THF/ hexane, rosy red in THFlOEt2, brick red in THF). This precipitation took place faster in THFhexane or THF/ OEt2 than in THF. The presence of hexane or OEtz favors the precipitation of 2a and thus avoids its decom(13) Stanetty, P.; Koller, H.; Mihovilovic, M. J. Org. Chem. 1992, 57,6833-6837. (14)Tables of the results are available as supplementary material. (15) 1 min, 30 min, 1 h, and 2 h at rt, 0 "C, -10 "C,-24 "C,and -40 "C, respectively, and 20 h at -78 "C.
J. Org. Chem., Vol. 60,No. 8, 1995 2503 position and reduces the amount of 3a formed through its lithiation. The effect of the temperature is not simple, but three significant facts were observed: (a) At temperatures above -24 "C, the lithiation was almost complete within 1 min after the addition of tBuLi, only little improvement being observed after 30 min. (b) The highest 2bl3b ratios are obtained a t 0 "C in THFhexane and at -10 "C in THFlOEt2 or THF, and they decrease when the temperature increases or decreases. (e) The proportion of unreacted ferrocene increases as the temperature decreases (from about 20%at rt to more than 60% a t -40 "C, no metalation occuring a t -78 "C even after 20 h). So there is a good midpoint, where yields and 2b/3b ratios are the highest ones, located around 0 "C in THFI hexane and -10 "C in THF/OEt2. Reactant Ratio.14 None of our experiments with equimolar amounts of 1 and the alkyllithium gave pure 2a, so the effect of reactant ratio was investigated. Metalations were performed using the best conditions found so far in THF/OEtP and THFhexane (e.g., 30 min a t -10 "C and 0 "C, respectively), with various tBuLi/l r a t i o P and external quenching by a n excess of "Bu3SnCl. Some general trends emerge from that study. First, conversions and 2bl3b ratios were always better in THFI hexane than in THFIOEt2, so we will only discuss the results obtained in THFhexane. The amounts of 2b and 3b increase as the tBuLi/l ratio increases, from 33 and 5%)respectively, when using 0.5 equiv of tBuLi (conversion of 38%)to 82 and 15%)respectively, when using 2 equiv of tBuLi (conversion of 97%). The 2b/3b ratio ranges from 5 to 8, the maximum being obtained for equimolar amounts of reactants, a decrease being observed when the proportion of tBuLi used increases or decreases. Finally, we conducted metalations of ferrocene in THFI hexane as above, using the same tBuLi/l ratios, but with decreasing amounts of "Bu3SnCl. In each case, there is a decrease of the formation of 2b and 3b, more important for 2b than for 3b. For example, using the conditions: lPBuLiPBu3SnCl= 11211, we obtained a 112bl3b ratio of 37151112%(instead of 3/82/15%for a reactant ratio of 1121 2.1). A large excess of "BuaSnCl thus has to be used in order to quench all the lithiated species formed and to give good yields of monosubstituted products. Stability of 2a. We wondered if 2a was a base strong enough t o metalate itself, thus giving 3a. This could explain that relatively large amounts of 3b were formed, even when using 0.5 equiv of tBuLi. According to the procedure of Wright,6 2a should be prepared cleanly through transmetalation of 2b using "BuLi. We thus performed transmetalations of isolated 2b (vide infra) with "BuLi in THF a t -78 "C and stirred reaction mixtures at different temperatures for 1 h. After quenching with Me3SiCl a t -78 "C, the products distribution was measured (Scheme 2, Table 2). There was no evidence of 1,l'-bis(trimethylsily1)ferrocene in any experiment, so no equilibration of the lithiated species occurred (Le. 2a is not strong enough to lithiate itself). (Trimethylsily1)ferrocene2c was the only product of the reaction performed at -78 "C, so the reaction between 2a and MeSSiCl is quantitative. At temperatures above -40 "C, 1 is present in significant amounts, establishing that 2a is not stable in THF. (16) tBuLi/l = 2, 1.5, 1.2,1, 0.8,and 0.5.
2504 J. Org. Chem., Vol. 60, No. 8,1995
Guillaneux and Kagan
Scheme 2
Scheme 3
-e -?
-Sn"Bu3
"BuLi THF -78°C
Fe
GD 2h
e
L
Fe
i
I hour TaC
Za
-e
~ p ~ c S n " B unBuLi 3 e Fe THF 2b
e -SiMe3 Fe + Fe e
I ) Me3SiCI
+Q3H%2
-78°C
1
2d-e
4 R = s, ' PTOl
2e
CI , X = OMenthyl
Scheme 4 -snnBu3
Fe
-10 -24 -40 -78
za
2c
67/33 72/28 75/25 83/17 9713
eR Fe
i RX (+Sn"k~ur)-
a:.,
in THJF
0
L
2 d R = PPh,. X
Table 2. Study of the Stability of Ferrocenyllithium (2a)
rt (25)
-78%
Fe
aa
PdClz(dppf)5 mOlo/o PhBr, CuO
-
DMF,lOO°C
2h
-Ph
Fe
a
+"BusSnBr
-
21
100/0
Experiments on a 1 mmol scale. 2a was prepared by adding 1.1equiv of "BuLi to 2b in 5 mL of THF a t -78 "C and stirring for 15 min at -78 "C. After stirring 1 h at the indicated temperature, quenching was realized by cooling to -78 "C, adding MeaSiCl, and standing for 1 h at rt. Determined by 'H NMR of the crude product. a
Consequently, mixtures of lithiated ferrocenes should be quenched rapidly when THF is used a s a part of the solvent . In the particular case of electrophiles which are able to substitute only one lithium atom of 3a, thus leading to the monosubstituted product after hydrolysis, the conditions found above should give good results: slow addition of 2 equiv of tBuLi to ferrocene in THFhexane a t 0 "C, stirring over 30 min, and quenching with excess electrophile should give yields in monosubstituted product above 85% (note that if 2a and 3a react too slowly, a decrease of the yield may be due to their partial decomposition in THF). In the case of electrophiles leading to disubstituted products upon reaction with 3a, the same conditions should give high yields of monosubstituted product (around 80%), but contaminated with 1,l'-disubstituted product. Preparation and Use of (Tri-n-butylstanny1)ferrocene. Since we could not find metalation conditions leading to 2a fully devoid of 3a, even for low conversions, it was necessary to look for a precursor of 2a wich could be easily prepared from ferrocene in one step and in good yield. Triorganostannyl ferrocenes seem to be amongst the best compounds for this purpose. (Trimethylstanny1)ferrocene was first prepared through direct lithiation of ferrocene and subsequent reaction with trimethyltin chloride, but stannylated products were unstable. We then selected 2b as a candidate for our project. Compound 2b was prepared on a 0.1 mol scale with the following conditions: lPBuLiPBu3SnCl = 1/2/1.5, metalation a t 0 "C over 30 min in THFhexane (l/l). The monosubstituted product 2b was isolated in a good yield (70%)by distillation.'' It is a red fluid oil which can be exposed to air and light for several months without perceptible decomposition. The transmetalation of 2b (17) Compound 2b was first described by Pellegrini, J. P.; Spilners, I. J., U.S. Patent 3,350,434, October 31, 1967. Chem. Abstr. 1968, 68, 49789g and by Dodo, T.; Suzuki, H.; Takiguchi, T. Bull. Chem. SOC. Jpn. 1970, 43, 288-290, both through direct lithiation of ferrocene, with yields not exceeding 11%.Butler et al. (ref 18)also prepared 2b on a large scale through direct lithiation of ferrocene, without description of the experiment.
using "BuLi was performed cleanly in THF at -78 "C, and subsequent reaction with PhzPCl gave (diphenylphosphino)ferrocene (2d)(78%isolated yield), with only tetran-butyltin as a byproduct (Scheme 3). Tetra-n-butyltin is a colorless apolar and fluid oil which can be easily removed through chromatography or crystallization of the product. The transmetalation is performed cleanly, since 2a prepared in this way reacts with 1.1 equiv of (S)-(-)menthyl p-tolylsulfinate to give (8)-ferrocenyl p-tolylsulfoxide (2e) with 96% ee in 90% yield (72%isolated yield of enantiomerically pure 2e). Little racemization occurred when using this procedure. We also attempted to perform the transmetalation of 2b into 2a in OEtz or hexane. In hexane, no transmetalation occured, even after one night a t room temperature. In OEtz, there was no reaction a t -78 "C,and the transmetalation was too slow a t room temperature, since after one night and subsequent reaction with MeaSiC1, 45% of 2b remained and 27% of l were present, coming from the degradation of 2a before quenching. The ability of 2b to undergo a Stille cross-coupling was then investigated. Using the conditions of Gronowitz et al.,19 phenylferrocene (2f)was prepared with a n isolated yield of 52% (Scheme 4). The direct synthesis of iodoferrocene from 4 was lastly investigated (Scheme 5). The Fc-Sn bond is readily cleaved by iodine in CH&12,1S leading to pure iodoferrocene (2g) (74%isolated yield).
Conclusion We carried out a detailed study of the direct lithiation of ferrocene. We significantly improved the procedure and prepared (tri-n-butylstanny1)ferrocene(2b)with a n overall isolated yield of 70% from ferrocene. It proved to be a precursor of choice for the synthesis of many monosubstituted ferrocenes, considering its ability to undergo either transmetalation with "BuLi, Stille crosscoupling, or metal-halogen exchange. (18)Butler, I. R.; Wilkes, S. B.; McDonald, S. J.; Hobson, L. J.; Taralp, A.; Wilde, C. P. Polyhedron 1993, 12, 129-131. (19) Gronowitz, S.; Bjork, P.; Malm, J.; Hornfeldt, A.-B. J . Organomet. Chem. 1993,460, 127-129.
J. Org. Chem., Vol. 60,No. 8, 1995 2505
High Yield Synthesis of Monosubstituted Ferrocenes
Experimental Section General. Ferrocene and lithium bases were purchased from Janssen. Concentrations were checked before each experiment.20 THF was distilled from sodium benzophenone ketyl and hexane from CaHz. DMF was degassed and stored over molecular sieves. Melting points are uncorrected. lH NMR and 13CNMR were obtained at 250 MHz and 62.9 MHz, respectively, in CDC13 solution; chemical shifts (6) are relative t o external TMS. 31PNMR were obtained at 101.3 MHz in CDC13 solution; chemical shifts (6) are relative t o external H3PO4. Optimization Experiments for the Metalation of Ferrocene. A 1.86 g amount of 1 (10 mmol) was stirred for 30 min in the appropriate amount of dry solvent under argon at rt and then cooled to the appropriate temperature. Alkyllithium was added via syringe to the finely divided partly insoluble 1 thus obtained, at a rate of approximately 1mmoll min. The reaction mixture was then stirred for the appropriate period, the nBu3SnC1was added, and the reaction mixture was allowed to warm to room temperature and stirred for an additional 1 h. Hydrolysis was performed with 10 mL of a 2 M aqueous sodium hydroxide solution, the aqueous layer was extracted with 20 mL of OEtz, and the ethereal layer was washed with 10 mL of brine and 10 mL of water, dried over MgSOd, and concentrated t o dryness. lH NMR of the crude product was performed in CDCl3 and product ratios were determined by integration of the ferrocenyl protons (1: 4.14 ppm, s, 10 H; 2b: 4.01 ppm, m, 2 H, 4.09 ppm, s, 5 H, 4.32 ppm, m, 2 H; 3b: 3.96 ppm, m, 4 H, 4.23 ppm, m, 4 H17). (Tri-n-butylstanny1)ferrocene(2b).I7 A 18.6 g amount of 1 (0.1 mol) was stirred for 30 min in 50 mL of dry THF and 50 mL of dry hexane under argon at rt and then cooled to 0 "C. A 135 mL volume of a 1.5 M solution of tBuLi in pentane (0.2 mol) was added over 90 min. The mixture was stirred another 30 min before 40.7 mL of "Bu3SnCl was added over 20 min. The hydrolysis was performed after 90 min with aqueous NaOH. The product was extracted with OEtz, the organic layer washed with brine and water and dried over MgS04, and the solvents were evaporated to dryness, giving 56 g of crude product as a red oil, which was taken up in hexane and filtered through neutral alumina. After evaporation of the solvents and sublimation of remaining 1 (80 "C, 1 mmHg), 33.0 g of 2b was obtained as a red oil from vacuum distillation (140 "C, 0.05 mmHg; lit.17188-190 "C, 0.15 " H g ) for an isolated yield of 70%: lH NMR 6 0.9 (m, 9H), 1.0 (m, 6H), 1.3 (m, 6H), 1.5 (m, 6H), 4.0 (m, 2H), 4.1 (9, 5H), 4.3 (m, 2H); 13CNMR 6 10.2 (3C), 13.7 (3C), 27.4 (3Q29.2 (3C), 67.9 (5C), 68.6 (lC), 70.2 (2C), 74.6 (2C);MS (EI) m l z 475 (23, M+), 418 (loo), 304 (95), 185 (93). Anal. Calcd for CzzH36FeSn: c, 55.63%;H,7.64%;Fe, 11.75%;Sn, 24.98%. Found: C,56.10%; H, 7.83%; Fe, 11.36%; Sn, 24.70%. (Dipheny1phosphino)ferrocene(2d). A 475 mg amount of 2b (1mmol) was dissolved in 5 mL of dry THF under argon at -78 "C. A 0.7 mL volume of a 1.6 M solution of "BuLi in hexane (1.1 mmol) was slowly added over 5 min, and the reaction mixture was stirred for 15 min at -78 "C, as a precipitate of 2a appears (the progress of the transmetalation can be monitored by TLC: SiOhexane, Rf: Fc 0.7, FcSnnBu3 0.75). A 0.2 mL volume of PhzPCl(1.1mmol) was then added, and the reaction mixture was stirred for 1h at rt before water was added, The products were extracted with OEtz, washed with aqueous NaOH, brine, and water, and dried over MgSO4 and the solvents evaporated. Recrystallization from hot hexane/OEb gave 290 mg of pure 2d (78%yield) as light brown flakes: mp 123-124 "C (lit.,z1122-123 "C); lH NMR 6 4.1 (s, 5H), 4.15 (m, 2H), 4.4 (m, 2H), 7.3-7.5 (m, 10H);13CNMR 6 69.0 (5C), 70.7 (d, Jpc = 3.7 Hz, 2C), 72.8 (d, Jpc = 14.8 Hz, 2C), 75.7 (d, Jpc = 5.7 Hz, lC), 128.0 (2C), 128.3 (d, Jpc = 17.7 Hz, 4C), 133.4 (d, Jpc = 19.3 Hz, 4C), 140.0 (d, Jpc = 10.0 Hz, 2C); 31PNMR 6 -15.9; MS (EI) m l z 370 (100, M+), 293 (21), 121 (10). Anal. Calcd for CzzHlgFeP: C, 71.37%; H, 5.18%; P, 8.37%. Found: C, 71.34%; H, 5.18%;P, 8.12%. (20) Suffert, J. J. Org. Chem. 1989,54, 509-510. (21) Kotz, J. C.;Nivert, C. L. J. Organomet. Chem. 1973,52,387406.
(S)-Ferrocenyl p-Tolyl Sulfoxide (2e). A 50 mmol volume of 2a was prepared as above from 23.75 g of 2b (50 mmol) in 125 mL of dry THF under argon at -78 "C and 35.7 mL of a 1.4 M solution of nBuLi in pentane (50 mmol). This mixture was added over a 75 min period to 16 g of (E+(-)menthyl p-tolylsulfhate (54 mmol) in 100 mL of dry THF under argon at -24 "C. The mixture was stirred for 10 min at -24 "C before water was added. The products were extracted with ether, the organic layer washed with aqueous NaOH, brine, and water, dried over MgS04, and the solvents were evaporated. A 14.6 g amount of pure 2e (90%yield) was obtained after chromatography over silica gel (elution with hexanelOEtz 50l50 and then OEtz). This product had an ee of 96% (Chiralcel OD-H, elution with hexaneli-PrOH 90l10, flow rate 0.5 mumin, 1 = 254 nm, retention times: (R)-2e 21.7, (S)-2e 25.4). An 11.8 g amount of enantiomerically pure product was obtained through rectrystallization from hot OEtz (72% isolated yield) as thin yellow needles: mp 142-144 "C; [ a ]=~+314 (c = 0.56, CHC13, 100% ee, Chiralcel OD-H, same conditions as above); 'H NMR 6 2.3 (s, 3H), 4.3 (m, lH), 4.4 (s+m, 7H), 4.6 (m, lH), 7.2 (m, 2H), 7.5 (m, 2H); 13CNMR 6 20.9 (3C), 64.6 (2C),67.2(2C), 69.2 (5C), 94.0 ( 1 0 , 123.7 ( 2 0 , 129.0 (2C), 140.3 (lC), 142.3 (E); MS (EI) m l z 324 (100, M+), 308 (60), 185 (251, 121 (81),91(57),56 (82). Anal. Calcd for C17H16FeOS: C, 62.98%; H, 4.98%; S, 9.89%. Found: C, 62.91%; H, 4.71%; S, 9.98%. Phenylferrocene (2f). A 37 mg amount of PdClz(dppf)(50 pmol), 95 mg of CuO (1.2 mmol), 5 mL of dry DMF, and 160 pL of PhBr (1.2 mmol) were heated to 150 "C under argon for 30 min in a Schlenk tube equipped with a reflux condenser and then cooled to rt. A 475 mg amount of 2b (1mmol) was then added and the reaction mixture stirred for 2 h at 100 "C. The mixture was filtered through Celite, extracted with OEtz, washed with aqueous HC1, brine, and water, and finally dried over MgS04, and the solvents were evaporated. Filtration over silica gel and subsequent recrystallization from aqueous ethanol gave 135 mg of pure 2f (52% yield) as orange flakes: 111-112 "C); lH NMR 6 4.0 (9, 5H), mp 111-113 "C 4.3 (m, 2H), 4.6 (m, 2H) and 7.1-7.5 (m, 10H); 13C NMR 6 66.5 (2C),66.9 (lc),68.8 (2C),69.5 (5C), 125.9 (lC),l26.1(2C), 128.3 (2C), 139.1 (1C); MS (EI) m l z 262 (100, M+), 141 (151, 121 (27). Anal. Calcd for C16H14Fe: C, 73.31%; H, 5.39%. Found: C, 73.08%; H, 5.52%. Iodoferrocene (2g). A 1.4 g amount of iodine (5.5 mmol) was added to 2.38 g of 2b (5 mmol) in 20 mL of CHzClz at rt. The mixture was stirred over 18 h, then washed with aqueous sodium thiosulfate, and filtered through neutral alumina, and the solvents were evaporated. The crude product was taken up in MeOH, and 1 g of KF was added to precipitate the stannylated byproducts, which were eliminated by filtration through neutral alumina. The MeOH was evaporated, the product was extracted with OEtz, washed with water, and dried over MgS04 and the solvents were evaporated. Recrystallization from pentane afforded 1.15 g of pure 2g (74%yield) as brownish orange flakes: mp 44-45 "C (lit.,444-45 "C); lH NMR 6 4.1 (m, 2H), 4.2 (8, 5H), 4.4 (m, 2H); 13CNMR 6 68.8 (2C), 71.0 (5C), 74.4 (2C);MS (EI) m l z 312 (100,M+),184 (33). Anal. Calcd for CloHSFeI: C, 38.51%; H, 2.91%. Found: C, 38.85%; H, 2.99%.
Acknowledgment. We thank CNRS for its financial support. One of us (D.G.) acknowledges DRET for a fellowship. Supplementary Material Available: Results obtained in the study of the influence of the conditions of the metalation and the reactant ratios (2 pages). This material is contained in libraries on microfiche, immediately follows this article in the microfilm version of the journal, and can be ordered from the ACS; see any current masthead page for ordering information.
J0941943F (22) Pauson, P. L.;Sraga, J.; Stefan, T.J.Chem. SOC.,Perkin Trans. 1 1985,1233-1235.
