5704
Organometallics 1995, 14, 5704-5707
Notes Facile Retro-[1,4]-Brook Rearrangement of a [(2-Siloxycyclopentyl)methyl]lithiumSpecies Xing-Long Jiang and William F. Bailey* Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269 Received August 9, 1995@
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Summary: The [1,41-0 C migration of the TBDMS group in the [(2-(tert-butyldimethylsiloxy)cyclopentyl)methylllithium system (1 and 2) has been found to be confined to the cis-isomer (1). The relatively facile [1,2]-migration of a silyl substituent from carbon to oxygen, first recognized by Brook in the late 1950's,' is the prototype of a class of [l,nl-C 0 silyl migrations that are commonly termed Brook rearrangements.2 More recently, examples of the reverse of this process, involving transfer of a silyl substituent from oxygen t o a formally anionic carbon (retro-Brook rearrangement), have been do~umented.~ In light of the current interest in [1,41-and [1,51-0 C silyl migration^,^ we were prompted to communicate the results of a study of [(2-(tert-butyldimethylsiloxy)cyclopenty1)methylllithiums (1and 2) demonstrating that the retro-[1,4]-Brook rearrangement in this system is confined exclusively to the cis-isomer (1).
eroatomic substituent^,^ we had occasion to explore the ring-closure of [4-(tert-butyldimethylsiloxy)-5-hexenylllithium (3)generated, as shown below, from iodide 4by low-temperature lithium-iodine exchange with t-BuLi6 2.2 t-BuLi
')
/
1. additive
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-
CH2 Li
-
No reaction
\
2
In the course of a continuing investigation of the cyclization of 5-hexenyllithiums bearing various hetAbstract published in Advance ACS Abstracts, November 1,1995. (1)Brook, A. G.J . Am. Chem. SOC. 1958,80,1886. (2)(a) Brook, A. G. Acc. Chem. Res. 1974,7, 77. (b) Brook, A. G.; Bassindale, A. R. In Rearrangements in Ground and Excited States; De Mayo, P., Ed.; Academic Press: New York, 1980;Vol. 2,p 149.( c ) Colvin, E.W. In Silicon in Organic Synthesis; Butterworths: London, 1981; p 30. (3)(a) West, R.;Lowe, R.; Stewart, H. F.; Wright, A. J.Am. Chem. SOC. 1971,93,282.(b) Wright, A.; West, R. J . Am. Chem. SOC.1974, 96,3214.( c ) Evans, D. A.; Takacs, J. M.; Hurst, K. M. J.Am. Chem. SOC. 1979,101,371.(d) Eisch, J. J.; Tsai, M. R. J . Organomet. Chem. 1982,225,5 and references therein. (e) Linderman, R. J.; Ghannam, A. J.Am. Chem. SOC. 1990,112,2392. (4)(a)For a concise summary of the literature relating to [1,41-and [1,5l-Brook and retro-Brook rearrangements, see: Lautens, M.; Delanghe, P. H. M.; Goh, J. B.; Zhang, C. H. J. Org. Chem. 1995,60, 4213.(b) Bures, E.J.; Keay, B. A. Tetrahedron Lett. 1987,28,5965. ( c ) Spinazze, P. G . ;Keay, B. A. Tetrahedron Lett. 1989,30,1765 and references therein. (d) Kim, K. D.; Magriotis, P. A. Tetrahedron Lett. 1990,31,6137. (e) Hoffmann, R.W.; Bewersdorf, M. Tetrahedron Lett. 1990,31, 67. (0 Hoffmann, R.;Brtickner, R. Chem. Ber. 1992,125, 2731.(g) Clayden, J.;Julia, M. Synlett 1996,103. @
5 no additive: TMEDA:
. .
6
. .
7
- 65 %
-20%
-6%
-7%
-15%
-60%
Quenching reaction mixtures that had been warmed and held at 0 "C for 1h delivered not only the expected cis(5) and trans-2-methyl-l-(tert-butyldimethylsiloxy)cyclopentane (6) products7but also a small quantity of cis2-[(tert-butyldimethylsilyl)methyllcyclopentanol(7).Moreover, alcohol 7 becomes the major product of the isomerization when the cyclization of 3 is conducted at higher temperatures or, as illustrated below, in the presence of N,N,iV'JV'-ktramethylethylenediamine (TMEDA). In no instance was the trans-isomer of 7 detected in any of the reaction mixtures nor was there any evidence of [1,51-0 C TBDMS migration in 3. Alcohol 7 is undoubtedly formed via retr0-[1,4]-Brook rearrangement following cyclization of 3. We were intrigued by the fact that TBDMS migration was apparently limited to the cis-isomer of the cyclic organolithium (1). In order to confirm this observation, the behavior of authentic samples of cis- (1)and trans-[(2~tert-butyldimethylsiloxy)cyclopentyl)methylllithium(2) was investigated. To this end, [4-(tert-butyldimethylsiloxy)-5-hexenyl)lithium (3)was isomerized for 1h at 0 "C in a solution
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( 5 )The results of study of the cyclization of (4-methoxy-5-hexeny1)lithium have been published: Bailey, W. F.; Jiang, X-L. J . Org. Chem. 1994,59,6528. (6)Bailey, W.F.;Punzalan, E. R. J . Org. Chem. 1990,55,5404. (7)Cyclization of 3 under a variety of experimental conditions has been found to give cis-rich mixtures of 5 and 6 . It is of some interest to note that the stereochemistry of the cyclization of the related ether, (4-methoxy-5-hexenyl)lithium, is strongly dependent on the solvent system in which the isomerization is conducted.6 The diastereoselectivity of the ring-closure of 3 and related substrates will be presented in the full account of an ongoing investigation of the cyclization of a range of 5-hexenyllithiums bearing heteroatomic substituents capable of coordination with lithium.
0276-733319512314-5704$09.00/00 1995 American Chemical Society
Notes
Organometallics, Vol. 14,No. 12,1995 5705 Scheme 1
9
6
2
- 100%
Table 1. Retro-[l,U-Brook Rearrangement (Scheme 1) of cis-[(2-(tert-Butyldimethylsiloxy)csclo~entsl)methslllithium(lIu
conducted at 0 "C in a solvent mixture containing 2.2 equiv of TMEDA (Table 1,entry 2). In striking contrast to the behavior of 1, the trans-isomer, 2, proved to be uroducts. totally resistant to retro-[1,4]-Brook rearrangement. entry temp, %yieldb Indeed, a series of experiments in which solutions of 2 no. solvent svst "C 7 5 stood at room temperature in the presence of TMEDA 1 n-CsH1z-EtzO (3:2by vol) +20 83 17 (or other Lewis bases) for periods of 1-2 h provided no 2 TMEDA 0 88 12 evidence of rearrangement: quenching such mixtures 3 f22 83 17 delivered pure truns-2-methyl-l-(tert-butyldimethylsi4 HMPA 0 80 20 1oxy)cyclopentane(6) in essentially quantitative yield a cis-[(2-(tert-Butyldimethylsiloxy)cyclopentyl)methyl]lithium (1) 1). (Scheme was generated a t -78 "C by addition of 2.2 equiv of t-BuLi to a solution of iodide 8 in n-pentane-diethyl ether (3:2by vol). Where The complete absence of any product derived from indicated, 2.2 molar equiv of dry TMEDA or HMPA was added a t C migration of the silyl substituent in 2 [1,41-0 -78 "C after completion of the exchange reaction. The cooling implies that intermolecular rearrangement is not ocbath was then removed, and the mixture stood at the specified temperature for 1.5 h before the addition of a n excess of oxygencurring in this system.8 This conclusion was confirmed free methanol. Yields were determined by capillary GC using by the result of the following experiment: a 2:l mixture n-heptane a s a n internal standard. of iodides 8 and 9 in n-pentane-diethyl ether (3:2 by vol) was treated with t-BuLi at -78 "C, and the of n-pentane-diethyl ether and the resulting cyclic resulting mixture of 1 and 2 was warmed and stood at organolithium products (1 and 2) were trapped with +20 "C for 1 h prior to quench. As expected (Table 1, iodine to deliver a mixture of the corresponding iodides entry 1,and Scheme 11, all of the trans-isomer (2) was (8 and 9) along with a small amount of 7. Careful recovered as 6 while 85% of the cis-isomer (1) was converted to 7. I 22 t-BuLi i.O"C, I h Given the intramolecular nature of the retro-[l,41Brook rearrangement in the [(2-(tert-butyldimethylsi-78 "C loxy)cyclopentyl)methylllithium system, it is perhaps 4 not surprising, albeit in retrospect, that migration is confined to the cis-isomer (lh9The [1,41-0 C migration of the TBDMS group in 1 may proceed, either in a concerted fashion or via the intermediacy of a pentavalent silicon intermediate,4 with little distortion of the 0 9 carbon skeleton. Such intramolecular migration would 68 % 20 % be energetically costly in the trans-isomer (2) since it would involve severe steric strain in the transition state chromatography of the product mixture on silica gel for the process. provided pure samples of 8 and 9 in isolated yields of 68% and 20%, respectively. Treatment of either 8 or 9 The generation of a lithium alkoxide following retrowith t-BuLi at -78 "C returned isomerically pure [1,4l-Brookrearrangement of 1 presumably provides the organolithium (1 or 2) in virtually quantitative yield as thermodynamic driving force for the r e a ~ t i o n . ~Lit-~ demonstrated by the fact that quench of each reaction erature precedent suggests that replacement of lithium mixture with MeOH at -78 "C delivered the correby sodium should reverse the direction of the migrasponding cis- (5) or truns-2-methyl-l-(tert-butyldimeth- t i ~ n . ~Indeed, - ~ as illustrated below, treatment of cisylsi1oxy)cyclopentane(6) in 97%-99% yield. 2-[(tert-butyldimethylsilyl)methyllcyclopentanol(7)with With a method in hand for the generation of isomeri5 equiv of NaH in DMF at room temperature led to cally pure samples of 1 and 2, the tendency of each virtually complete conversion of the alcohol to 5. isomer to undergo retro-[1,4l-Brookrearrangement was explored (Scheme 1). As demonstrated by the results C silyl migrations are ( 8 ) Intermolecular [1,4]- and [1,51-0 summarized in Table 1, [1,4]-migration of the TBDMS documented; see, for example: Smichen, G.; Pfletschinger, J. Angew. moiety in 1 is a facile, high-yield process at room Chem, Int. Ed. Engl. 1976,15,428. (9) It is of some interest to note that intramolecular retr0-[1,4]-Brook temperature in n-pentane-diethyl ether solvent o r a t rearrangement is a facile process for the trans-isomer of the related 0 "C in the presence of TMEDA or HMPA pure 7 was [(2-siloxycyclohexyl)methyl]lithium system. See: Rucker, C. Tetruhedron Lett. 1984,25,4349. isolated in 85%yield when the rearrangement of 1 was
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5706 Organometallics, Vol. 14, No. 12, 1995
Notes
combined extract and washings were washed successively with 20 mL of aqueous ammonium chloride, 20 mL of water, and 20 mL of brine, dried (MgS041, and concentrated under reduced pressure. The residue was purified by preparative 5 GC on a 10-ft, 10% FFAP on Chromosorb W NAW (801100 7 94 % mesh) column at 150 "C t o afford 1.95 g (91%) of the title compound: 'H NMR 6 0.023 (s, 6 H), 0.88 (s, 9 H), 0.93 (d, J = 6.63 Hz, 3 H),1.55-1.75 (m, 7 HI, 3.99-4.01 (m, 1 HI; Experimental Section NMR 6 -4.89, -4.59, 14.34, 18.40, 21.96, 25.91, 30.85, 35.11, 39.99, 76.33. Anal. Calcd for ClzH260Si: C, 67.22; H, 12.22. General Procedures. General spectroscopic and chroFound: C, 67.46; H, 12.43. matographic procedures, methods used for the purification of reagents and solvents, and precautions regarding the maniputrans-2-Methyl1-(tert-butyldimethy1siloxy)cyclopenlation of organolithiums have been previously described.I0 tane (6). A solution of 0.500 g (10.0 mmol) of trans-2methylcyclopentanol,5 0.910 g (6.00 mmol) of tert-butyldimeLiterature procedures, incorporating some minor modificathylsilyl chloride, and 0.850 g (12.5 mmol) of imidazole in 1.5 tions, were followed for the preparation of 6-chloro-1-hexenmL of dry DMF was heated at 35 "C for 24 h. The cooled 3-01,'' trans-2-methylcyclopentan01,~ cis-2-methylcyclopenreaction mixture was worked up as described above for the tan01,~and 1-hexen-3-oL5 cis-isomer, and the residue was purified by preparative GC 3-[(tert-Butyldimethyl)eiloxyl-6-iodo-l-hexene (4). A on a 10-ft, 10% FFAP on Chromosorb W NAW (801100 mesh) solution of 7.50 g (55.8 mmol) of 6-chloro-l-hexen-3-ol,11 9.48 column at 150 "C to afford 0.950 g (89%) of the title comg (139 mmol) of imidazole, and 10.1 g (66.9 mmol) of tertpound: 'H NMR 6 0.029 (s, 3 H), 0.039 (e, 3 H), 0.89 (s, 9 H), butyldimethylsilyl chloride in 18 mL of dry DMF was heated 0.93 (d, J = 6.63 Hz, 3 H), 1.48-1.84 (m, 7 H), 3.58-3.61 (m, at 35 "C for 24 h and then diluted with 40 mL of diethyl ether. 1 H); 13C NMR 6 -4.68, -4.49, 18.08, 18.14, 21.23, 25.93, The resulting mixture was poured into 20 mL of water, the 31.17, 34.36, 42.51, 80.89. Anal. Calcd for CIZHZ~OS~: C, organic layer was separated, and the aqueous phase was 67.22; H, 12.22. Found: C, 66.79; H, 12.32. extracted with several portions of diethyl ether. The combined cis- (8)and truns-2-(Iodomethyl)-l-(tert-butyldimethorganic extracts were washed sequentially with 30 mL of ylsi1oxy)cyclopentane(9).A 100 mL flame-dried flask was saturated aqueous ammonium chloride solution, 30 mL of charged with a solution of 1.85 g (5.45 mmol) of 3-(tertwater, and 30 mL of brine, dried (MgSOd), and concentrated butyldimethyl)siloxy-6-iodo-l-hexene(4) in 32.7 mL of dry a t reduced pressure. The residue was purified by flash pentane and 21.8 mL of dry diethyl ether. The solution was chromatography on silica gel (petroleum ether; R f = 0.67) to cooled to -78 "C, and 6.32 mL of a 1.89 M solution of t-BuLi give 11.2 g (81%)of the TBDMS ether, which was used without (11.9 mmol) in pentane was added dropwise by syringe. The further purification for the preparation of the iodide: 'H NMR resulting mixture was stirred at -78 "C for 5 min, the cooling 6 0.027 (s, 3 H), 0.048 (s, 3 H), 0.89 (s, 9 H), 1.26-1.80 (m, 4 bath was then removed, and the solution was warmed and H), 3.53 (t, J = 6.68 Hz, 2 H), 4.13-4.15 (m, 1 HI, 5.04 stood at 0 "C for 1 h to effect cyclization to a mixture of 1 and (apparent d oft, J,, = 10.5 Hz, Jgem= 1.48 Hz, 4J= 1.46 Hz, 2. In another flask, a solution of 2.79 g (10.9 mmol) of iodine 1 H), 5.15 (apparent d oft, Jtr,, = 17.1 Hz, 4J = 1.55 Hz, Jgem in 35 mL of dry diethyl ether was cooled to -78 "C under an = 1.48 Hz, 1H), 5.78 (ddd, Jtrans = 17.1 Hz, Jc,s = 10.5 Hz, 3J atmosphere of argon. The solution of 1 and 2 was then added = 5.91 Hz, 1 H); NMR 6 -4.86, -4.37, 22.63, 25.87, 28.33, dropwise to the iodine solution via a Teflon cannula. The 35.20, 45.24, 73.08, 114.07, 141.31. resulting mixture was stirred at -78 "C for 0.5 h and was then A solution of 7.00 g (46.6 mmol) of sodium iodide and 5.30 warmed to room temperature and poured into 20 mL of 5% g (21.3 mmol) of the chloride in 70 mL of dry acetone was aqueous sodium thiosulfate. The organic phase was separated, heated at gentle reflux for 24 h. The reaction mixture was washed with brine, dried over MgS04, and concentrated under cooled and filtered, and the precipitate was washed with reduced pressure. Flash chromatography of the residue over acetone. The combined filtrate and washings were concensilica gel using hexanes as eluent served to separate the trated, and the residue was taken up in 50 mL of diethyl ether. thermally and light-sensitive isomeric products. The major The ethereal solution was washed with 30 mL of 5% aqueous product (1.25 g, 68%), which eluted first (Rf = 0.571, was sodium thiosulfate and 30 mL of brine, dried (MgSOd), and identified as cis-2-(iodomethyl)-l-(tert-butyldimethylsiloxy)concentrated under reduced pressure. The residue was puricyclopentane (8) on the basis of the following spectroscopic fied by flash chromatography on silica gel (petroleum ether) data: IH NMR 6 0.06 (s, 3 H), 0.10 (s, 3 H), 0.88 (s, 9 HI, 1.39to give 6.31 g (87%) of the title iodide which was pure by GC 1.45 (m, 1 H), 1.67-1.87 (m, 5 HI, 2.09-2.24 (m, 1 HI, 3.15 (A analysis: (petroleum ether; R f = 0.70) IH NMR 6 0.014 (s, 3 portion of ABX, JAB= 9.19 Hz, Jm = 6.56 Hz, 1 H), 3.28 (B H), 0.037 (s, 3 H), 0.884 (s, 9 H), 1.48-1.93 (m, 4 HI, 3.18 (t, portion of ABX, JAB= 9.19 Hz, JBX= 8.75 Hz, 1H), 4.17-4.18 J = 5.53 Hz, 2 HI, 4.11-4.13 (m, 1 H), 5.03 (apparent d oft, (m, 1 HI; 13C NMR 6 -4.62, -4.33, 7.43, 18.03, 22.31, 25.86, J,,, = 10.3 Hz, Jgem= 1.48 Hz, 4J= 1.34 Hz, 1 H), 5.14 29.67, 34.99, 49.92, 74.86. HRMS calcd for C8H16ISiO (M+ (apparent d o f t , Jt,, = 17.1 Hz, 4J= 1.52 Hz, J,,, = 1.48 C4Hg) mlz 283.0015, found mlz 283.0009. The minor product Hz, 1H), 5.77 (ddd, Jt,,, = 17.1 Hz, J,,, = 10.3 Hz, 3J= 6.00 (0.377 g, 20%;Rf = 0.29) was identified as truns-2-(iodomethyl)Hz, 1 H); 13C NMR 6 -4.85, -4.39, 7.11, 25.86, 29.17, 32.46, 1-(tert-butyldimethy1siloxy)cyclopentane(9) on the basis of the 38.65, 72.72, 114.06, 141.16; HRMS calcd for C8H16ISiO (M+ following spectroscopic data: 'H NMR 6 0.04 (s, 3 H), 0.07 (s, - C4H9) mlz 283.0015, found mlz 283.0012. 3 H), 0.88 (s, 9 HI, 1.23-1.29 (m, 1 HI, 1.51-1.62 (m, 1 H), cis-2-Methyl1-(tert-butyldimethy1siloxy)cyclopen1.68-1.91 (m, 5 H), 3.16 (A portion of ABX, JAB= 9.65 Hz, tane (5). A solution of 1.00 g (10 mmol) of cis-2-methylcycloJ m = 6.80 Hz, 1 H), 3.33 (B portion of ABX, JAB = 9.65 Hz, pentan01,~1.81 g (12.0 mmol) of tert-butyldimethylsilyl chloJBX= 4.38 Hz, 1 H), 3.74-3.77 (m, 1 H); I3C NMR 6 -4.57, ride, and 1.70 g (25.0 mmol) of imidazole in 2.5 mL of dry DMF -4.36, 12.17, 17.97, 21.71, 25.85, 30.05, 34.71, 49.62, 78.30. was heated at 35 "C for 24 h. The cooled reaction mixture HRMS calcd for CBHIGIS~O (M+ - C4Hg) mlz 283.0015, found was diluted with 25 mL of water and 30 mL of diethyl ether, mlz 283.0019. the layers were separated, and the aqueous layer was exRetro-[1,4]-BrookRearrangement: Preparation of cistracted with two 20 mL portions of diethyl ether. The 2-[(tert-butyldimethylsilyl)methyllcyclopentanol(7). An approximately 0.1 M solution of ci~-2-(iodomethyl)-l-(tert(10)Bailey, W. F.; Khanolkar, A. D.; Gavaskar, K.; Ovaska, T. V.; butyldimethylsi1oxy)cyclopentane (8) in n-pentane-diethyl Rossi, K.; Thiel, Y.; Wiberg, K. B. J . Am. Chem. SOC.1991,113, 5720. ether (3:2 by vol) containing an accurately weighed quantity (11) Meyer, C.; Marek, I.; Courtemanche, G.; Normant, J.-F.Tetof n-heptane as internal standard was cooled to -78 "C, and rahedron 1994,50,1665.
Notes 2.2 molar equiv of t-BuLi in pentane was added dropwise via syringe over a 5 min period. The resulting mixture was stirred at -78 "C for 5 min before treatment in one of the following ways. (A)The cooling bath was removed, and the solution was warmed and stood at f 2 0 "C for 1.5 h before the addition of 1.0 mL of dry, deoxygenated MeOH. (B) The organolithium solution was maintained at -78 "C, and 2.2-2.5 equiv of dry TMEDA or HMPA was added by syringe. The resulting mixture was stirred for an additional 5 min at -78 "C and then was warmed and stood at the appropriate temperature (Table 1, entries 2-4) for 1.5 h prior to the addition of 1.0 mL of dry, deoxygenated MeOH. Reaction mixtures were washed with water, dried (MgSOJ, and concentrated under reduced pressure. GC analysis on a 19-m x 0.25-mm methylphenyl silicone capillary column using temperature programming (50 "C for 5 min, 20 "C/min to 250 "C) revealed that the product mixtures consisted of 5 and 7 in the ratios given in Table 1. The minor product, which had the shorter retention time, was identified as cis-2-methyl-l-(tert-butyldimethylsiloxy)cyclopentane (5) by comparison with an authentic sample. The major product, isolated in 85% yield from the reaction conducted in n-pentane-diethyl ether by chromatography on silica gel (50% diethyl ether-hexanes; Rf = 0.801, was identified as the title alcohol on the basis of the following spectroscopic data: IR (neat) 3374 (br), 2930, 1464, 1250, and 828 cm-l; 'H NMR 6 -0.039 (s, 3 H), -0.034 (s, 3 H), 0.53-0.59 (m, 2 H), 0.690.76 (m, 1 H), 0.86 (s, 9 H), 1.30 (br s, 1 H), 1.64-1.80 (m, 6 H), 3.96-3.98 (m, 1H); I3C NMR 6 -5.76, -5.02,11.49, 16.64, 22.24, 26.58, 31.28, 34.13, 41.92, 76.52. Anal. Calcd for C12H26Si0: C, 67.22; H, 12.22. Found: C, 67.16; H, 12.40.
Organometallics, Vol. 14, No. 12, 1995 5707 Repetition of these experiments using trans-2-(iodomethyl)-
1-(tert-butyldimethylsi1oxy)cyclopentane (9) gave no evidence of rearrangement: in each instance, pure truns-2-methyl-l(tert-butyldimethylsi1oxy)cyclopentane(6)was produced in ca. 100% yield.
[1,4]-Brook Rearrangement of cis-2-[(tert-butyldimethylsilyl)methyl]cyclopentanol(7): Preparation of c i s - 2 - M e t h y l - 1 - ( ~ e ~ - b u ~ l ~ e ~ y l(5). siloxy A suspension of 0.380 g (15.8 mmol) of oil-free sodium hydride in 5.0 mL of dry DMF was stirred under a blanket of argon, and 0.678 g (3.17 mmol) of cis-2-[(tert-butyldimethylsilyl)methyllcyclopentanol (7) was added to the suspension. The resulting mixture was stirred a t room temperature for 4 h, and then diluted with 5.0 mL of diethyl ether, washed with water, and dried over MgSOd. Analysis of the crude product methylphenyl silicone capillary by GC on a 19-m x 0.25" column using temperature programming (50 "C for 5 min, 20 Wmin to 250 "C) and by GC-MS on a 25-m x 0.20-mm HP-5 methylphenyl (20%) silicone capillary column using temperature programming (50 "C for 5 min, 20 "C/min to 250 "C) revealed that reaction mixture consisted of 94% cis-2-methyl1-(tert-butyldimethy1siloxy)cyclopentane (5) and 6% of the starting alcohol (7). The identity of the products was confirmed by comparison of GC retention times and mass spectra t o those of authentic samples.
Acknowledgment. This work was supported by the Connecticut Department of Economic Development. OM950631F
