J. O r g . Chem. 1984,49, 3928-3938
3928
centration and the remaining terms are already defined.
and considered isotropically in all refinements. Perspective drawings are given in Figures 1-4.
The singlet (@) and triplet (49 excitation yields were calculated ~ quantum yield for energy transfer from eq 7, where i # is~ the (7) from the chemienergized excited ketone to fluorophor, $F" the fluorescence yield of the fluorophor (F), and the $ F term ~ ~ as already defined. For the singlet excitation yields (@), 9,lO-diphenylanthracene (DPA) was used as fluorophor, for which b p = 1 . eand = bPAs = 1.00. For the triplet excitation yields (699,lO-dibromoanthracene(DBA) was used as fluorophor, for which &,BA' = 0.1024 and #m = ~ B = 0.25% A ~ The enhanced chemiluminescence data were processed on a Tektronix 4051 Computer and the results are summarized in Table 11. X-ray Crystallography. The orientation matrix and the cell parameters were determined from all clear colorless crystals of given dimensionson a SYNTHEX-P3 four circle diffractometer. Measurement of intensities: w scan, lorange, Mo Ka,2 8 maximum = 5 5 O . The structures were solved by direct-phase determination. Positional and thermal parameters could be refiied by anisotropic least-squares cycles to the given R values. The positions of the hydrogen atoms were calculated geometrically (23) Wilson, T.; Schaap, A. P. J. Am. Chem. SOC.1971, 93, 4136. (24) Wu,K.-C.; Ware, W.R. J . Am. Chem. SOC.1979,101,5906. (25) Berenfeld, V. M.; Chumaevesky, E. V.; Grinev, M. P.; Kuryatnikow, Yu. J.; Artmev, E.T.; Dzhagatapanyan, R. V. IZLJ.Acad. Nauk. SSSR Ser. Fiz 1970, 34,678.
~
Acknowledgment. We are grateful t o the Deutsche Forschungsgemeinschaft and t h e Fonds der Chemischen Industrie for generous financial support. We thank Dr. D. Scheutzow for measuring t h e 400-MHz 'H NMR a n d t h e 100.61-MHz 13C NMR spectra and Dr. G. Lange for measuring t h e mass spectra. Registry No. 3a, 255-37-8;3b, 4345-55-5;3c, 82912-44-5;3d, 82912-45-6; 3e, 5770-58-1;3e (alcohol), 5770-68-3;3f, 79792-92-0; ~ 3g, 82912-48-9; 3h, 82912-49-0;3i, 79792-91-9;3j, 75694-46-1;3j (alcohol),91201-75-1;3k, 91201-56-8; 31,91201-57-9;31 (alcohol), 91201-76-2; 4e, 91201-58-0; 4f, 91201-59-1; 4g, 91201-60-4; 4h, 91201-61-5; 4i, 91201-62-6; 4j, 91201-63-7; 4k, 91201-64-8; 41, 91201-65-9; 5a, 91201-66-0; 5e, 79792-93-1; 5f, 635-67-6; 5g, 91201-67-1; 5h, 91201-68-2; 5i, 79792-94-2; 5j, 643-94-7; 5k, 91201-69-3; 51, 91201-70-6; 6, 91201-71-7; 7f, 91201-72-8; 7g, 91201-73-9;7h, 91201-74-0; Br(CH2)2Br,106-93-4;Br(CH2),Br, 109-64-8; Br(CH2)4Br, 110-52-1; PhCOCH2Br, 70-11-1; PhCHBrCOPh, 1484-50-0;1,2-dihydroxybenzene,120-80-9;2,3dihydroxy-1-methoxybenzene,934-00-9; naphthalene-2,3-diol, 92-44-4. Supplementary Material Available: Positional and thermal parameters of the atoms of the dioxetanes 4g, 4h, and 4j, diester 5h, and dioxane 6 are given in Tables I-X; details of the crystallographic parameters in Table XI,perspective drawing of diester 5h; labeling of the atoms in the Figures 1-4 corresponds to that given in Tables I-X (13 pages). Ordering information is given on any current masthead page.
Substitution Reactions of Secondary Halides and Epoxides with Higher Order, Mixed Organocuprates, R2Cu(CN)Li2:Synthetic, Stereochemical, and Mechanistic Aspects Bruce H. Lipshutz,*+ Robert S. Wilhelm, Joseph A. Kozlowski, and David Parker Department of Chemistry, University of California, Santa Barbara, California 93106
Received J a n u a r y 9, 1984 Higher order cuprates, represented by the general formula R2Cu(CN)Li2,are readily prepared from copper cyanide and 2 equiv of an organolithium. These novel reagents react readily and efficiently with secondary unactivated iodides and bromides affording products of substitution. Likewise, mono-, di-, and trisubstituted epoxides undergo ring opening leading to the corresponding alcohols in excellent yields. The effects of solvent, temperature, gegenion, and variations in ligands are discussed. Replacement of the second equivalent of RLi by CH3Li strongly encourages transfer of R over CH3 in R(CH3)Cu(CN)Li2with halides. Use of PhLi as RRLi in place of one RpLi (i.e., Rp(Ph)Cu(CN)Li,) is suggested for oxirane cleavage. The stereochemicalimplications associated with both couplings are also addressed.
Introduction Among the vast array of methodologies available to the organic chemist, organocopper based reagents have provided one of the most consistently popular tools for carbon-carbon bond construction.l This is not surprising as copper salts are available in quantity, and reactions of reagents derived therefrom t e n d to be efficient a n d conditions mild.2 As with most useful methodologies, however, there are limitations which require alternative strategies for effecting the same net overall synthetic transformation. Thus, in t h e case of organocuprates R2CuLi, 1, displacement processes at secondary unadivated centers bearing halogen are quite rare due t o highly competitive A. P. Sloan Foundation Fellow, 1984-1986.
reduction and elimination pathway^.^^^ Likewise, substitution reactions of these "lower order" species 1 with, in particular, di- and trisubstituted epoxides are oftentimes problematic as both products of rearrangement and elimination are commonly e n c o ~ n t e r e d . ~ ?These ~ pitfalls notwithstanding, interest in t h e applications of cuprate chemistry have continued ~ n a b a t e d . ~ (1) Collman, J. P.; Hegedus, L. S. In "Principles and Applications of Organotransition Metal Chemistry";University of Science Books: Mill Valley, CA, 1980; pp 544-565. (2) Posner, G. H. Org. React. 1975,22, 253. (3) Whitesides, G. M.; Fiacher, W. F.; San Filippo, J.; Boahe, R. W.; House, H. 0. J. Am. Chem. SOC.1969, 91, 4871. (4) Hartman, B. C.; Livinghouse, T.;Rickbom, B. J. Org. Chem. 1973, 38,4346. Johnson, C. R.; Herr, R. W.; Wieland, D. M. Ibid. 1973,38,4263, J. Am. Chem. SOC.1970,92, 3813.
0022-326318411949-3928$01.50/0 0 1984 American Chemical Society
J. Org. Chem., Vol. 49, No. 21, 1984 3929
Substitution Reactions with Mixed Organocuprates Table I. Effects of Solvent on Substitution Reactions of &Cu(CN)Li2 with Cyclohexyl Iodide
4 -6
Table 11. Coupling Reactions of n -Bu2Cu(CN)Li2with Seconary Halides
solvent
THF EtzO PhCHs 1:l THF/EhO 1:l THF/PhCH3 DME
conditn 1.9 equiv, -78 OC, 1h 1.5 equiv, -50 "C, 1 h 1.9 equiv, -50 "C, 1 h 1.5 equiv, -50 OC, 1 h 1.5 equiv, -50 OC, 1 h 2.0 equiv, -78 OC, 1 h
yield," % >90 746 0' 6gd 61d >90
VPC. 26% starting material recovered. e All starting material recovered. dEssentially all the starting iodide waa consumed. a By
Recently, the concept of "higher order, mixed" copper reagents R2Cu(CN)Li2,2, was introduced wherein Cu(1) dilithium salts are formed in an ethereal solvent from copper cyanide and 2 equiv of an organolithium according to eq l.s These species display remarkably different 2RLi + CuCN R2Cu(CN)Li2 (1) chemical (and spectroscopic7)properties relative to Gilman reagents 1, allowing coupling between one of a variety of ligand types R affixed to copper and either secondary halidess or substituted epoxidess in excellent yields. In a full account of this subject, we now describe (1)the details of our preliminary (2) the role of solvent, gegenion(& and temperature, (3) the selectivity of ligand transfer from copper to carbon, and (4) in light of some preliminary stereochemical results obtained? additional experiments aimed at gaining insight into the mechanistic features of the coupling process.
dX dn-Ou n-BqCTrjyIL12-
n-BuzCu(CNILi2
n 1
x
1 2 2
yield, % 82 86 100 41
conditn -78 "C, 2 h 0 OC, 6 h -78 "C, 1h rt," 6 h
I Br I Br X
n-Bu
-An X I Br
c1
conditn -50 OC, 2 h 0 OC, 2 h; rt," 1 h rt: 11 h
yield, % 99 94 28
"rt = room temperature.
-
for mediating the coupling (with 2, R = n-Bu) appears to be THF. Although dimethoxyethane (DME) and EbO are also acceptable, large percentages of toluene should be avoided (Table I). In the cyclic series, both cyclohexyl and cyclopentyl iodides and bromides were investigated, along with 2-halopentanes as representative acyclic model systems, chosen for comparison purposes with the classical work3on lower order reagents. In the former class, all lead to good yields of the anticipated product, with bromocyclohexane being the only problematic case. This is to be expected3 based on the nature of the coupling process (vide infra). Secondary chlorides are also poor reaction partners. Table I1 summarizes this initial brief study, the results listed being quite striking by comparison with existing literature data.2~3J2In contrast to the remarkable Results and Discussion proclivity of reagents 2 toward displacement of secondary Reactions of Secondary Unactivated Halides. At iodides and bromides, secondary sulfonates (mesylates, the time that this initial work was begun: there were tosylates, and trisylates) are far less prone toward subnumerous literature reports attesting to the inefficiency stitution and generally do not lead to acceptable yields of associated with the coupling between a secondary unacproduct. It should be mentioned at this juncture that only tivated center bearing halogen and a Gilman c ~ p r a t e . ~ ~ca. ~ 1.5 equiv of 2 are routinely used. When, however, the Yields were rarely considered synthetically useful. In light ratio of cuprate to, e.g., tosylate is increased significantly of Ashby's extensive studies on substitution reactions of (e.g., 10 equiv), the efficiency of the process improves the higher order reagent Me3CuLiZ,10 which clearly demmarkedly, as in the case shown below. These observations onstrate that a unique species of considerable synthetic potential is formed from CUIand 3 equiv of MeLi, we set n-;;;:;::;,:;, out to prepare the mixed analogue substituting CuCN for CuX (X = I, Br). The reagents resulting from the combination of CuCN plus 2RLi'l are always colored, being (>80%) a function of the CuCN employed, and usually are formed are surprising in view of the well-established reactivity of at temperatures between -78 and -25 "C. Such solutions secondary tosylates toward lower order reagents, although of R2Cu(CN)Lizreact rapidly with secondary iodides at yields for these reactions are also in the moderate range.13 very low temperatures (-78 to -50 "C) whereas the corVariation in RLi. When 2-iodooctane was used as the responding bromides usually require ca. 0 "C. Using cysubstrate, ligand transfer from copper to carbon as a clohexyl iodide as a model substrate, the solvent of choice function of the nature of the organolithium was next examined. While primary alkyllithium derived reagents lead (5) For an up-to-date review on the chemistry of the higher order to very efficient carbon-carbon bond formation, cuprates organocuprates, see: Lipshutz, B. H.; Wilhelm, R. S.; Kozlowski, J. A. 2 formed from a secondary or aryllithium (e.g., s-BuLi or Tetrahedron Rep., in press. (6) Lipshutz, B. H.; Wilhelm, R. S.;Floyd, D. M. J. Am. Chem. SOC. PhLi) reacted to afford essentially products resulting from 1981,103, 7672. competing reduction and (some) elimination. It is par(7) Lipshutz, B. H.; Kozlowski, J. A,; Wilhelm, R. S. J. Org. Chem., ticularly noteworthy that vinyl ligands are readily delivered third paper in a series in this issue. in the case of secondary iodides. However, yields for the (8) Lipshutz, B. H.; Kozlowski, J. A.; Wilhelm, R. S. J. Am. Chem. SOC. 1982,104, 2305. same coupling with a bromide dropped considerably (9) Lipshutz, B.H.; Wilhelm, R. S. J. Am. Chem. SOC.1982,104,496. (35-40%), even in the presence of a 4-fold excess of 2, R (IO) Ashby, E. C.; Lin, J. J. J. Org. Chem. 1977,42, 2805.
L
(11) The addition of 1 equiv of an organolithium, RLi, to CuCN, thereby forming RCu(CN)Liwas first pioneered by Levisdes; cf. Gorlier, J. P.: Hanion. L.: Levisdes. J.: Warmon. J. Chem. Commun. 1973.88. For a more recent report, see: H&on,-L.; Levisdes, J. J.Orgummet. Chem. 1983, 251, 133.
(12) Ashby, E. C.; Lin, J. J.; Watkins, J. J. J.Orgummet. Chem. 1977, 42, 1099. Corey, E. J.; Posner, G. J. Am. Chem. SOC.1967, 89, 3911. (13) Johnson, C. R.; Dutra, G. A. J. Am. Chem. SOC.1973, 95, 7777.
3930 J. Org. Chem., Vol. 49, No. 21, 1984
Lipshutz et al.
Table 111. Variation of RLi in Reactions of R2Cu(CN)Li2 w i t h Secondary Halides
, -JOT. 2.5h
-L
CuCN t n-BuLi t MeLi Tx
R~C::,":)LI~
X Br
I I I I I I If
R CH2=CHCH2 CH2=CH CH3 CHSCH, CH3CH2CHZ
yield," % >gob 9oc 89 >95 90d
C6H6
n-Bu
2 Et
ratio RI:Ro 5.5:l 81 27:l 1:2.2 1:2.6 141 1.5:l
> Me > vinyl > phenyl.
precise information on the exact composition of the reagents themselves. Solvent Effects. In our preliminary studies on the ring-opening reactions of oxiranes with 2,8 THF had been chosen as solvent due to our early success with this me-
A4 9
'
67%
5
~
OH t starting material n-Bu
experiments, comparing THF and Ego, but at -40 OC for 1.5 h, vividly demonstrate the differences in relative rates of reaction which can occur as influenced by solvent. Likewise, treatment of epoxide 11 (Table V) with 2, R = vinyl, in Ego led to the expected homoallylic alcohol (>87% yield) in ca. half the time required for the same reaction run in THF. Summary It has been demonstrated, albeit in relatively simple
3934 J.
Org. Chem., Vol. 49,No.21, 1984
model systems, that higher order, mixed cuprates 2 and their second generation, more highly mixed analogues &RRCu(CN)Li2, 3, are superior to their lower order predecessors 1 in effecting substitution reactions of epoxides and unactivated halides. Secondary iodides generally couple between -78 and -50 "C, while bromides require between 0 "C and room temperature. THF appears to be the preferred solvent, although other ethereal media may also be utilized. Both lithium cations in solutions of 2 play a dramatic role in accelerating the coupling process, relative to Grignard derived reagents. The selectivity of ligand transfer is such that a methyl group can oftentimes successfully replace the second equivalent of &Li, permitting conservation of potentially valuable organic ligands. This does not apply, however, to olefin formation via (vinyl)MeCu(CN)Li2,as a methyl group is derived preferentially over a vinyl residue. The stereochemistry of the substitution process at carbon has been elucidated; secondary iodides afford racemic products, while bromides react with inversion of configuration. This outcome is dependent upon the nature of the substrate rather than the reagent, as essentially identical observations have been made from reactions with Gilman reagents 1. Epoxides couple with a variety of cuprates 2, the conditions required being a function of degree of substitution on the ring. Displacement occurs with control of both regio- and stereochemistry, the least hindered site in unactivated cases undergoing backside attack. An aryl ligand, which does not undergo transfer from copper to carbon in reactions of halides, will participate in opening epoxides. Relative to an alkyl group, however, it is sluggish and, hence, in more highly mixed species 3, RR = Ph, may permit selective transfer of &. As with halides, this is limited to & = alkyl, as poor selectivity is seen with & = vinyl.
Experimental Section NMR spectra were recorded with a Varian T-60, FT-80, XL100, or Nicolet NT 300 spectrometer in CDC13and are reported in 6 values. IFI spectra were measured on a Perkin-Elmer Model 283 spectrophotometer. Maas spectra were obtained on a W - 2 F instrument. VPC analyses were performed on a Hewlett-Packard Model 5880A gas chromatograph using a 6 f t X in. column packed with 20% SE 30 on Chromosorb W. Thin-layer chromatographic determinations employed 0.25-mm glass plates coated with silica gel purchased from Baker. Column chromatography was carried out by using Silica Gel-60 from Merck, 70-230 mesh. All syringes and glassware were oven-dried at 120 "C overnight prior to use. EbO and T H F were freshly distilled from sodium/benzophenone ketyl, while toluene was dried over CaH2. All reactions were run under a blanket of argon. Cuprous cyanide was obtained from MCB and used as received. I t was generally stored over KOH in an Abderhalden at 56 "C (refluxing acetone). Methyllithium (low halide) was purchased from Aldrich, phenyllithium, n-butyllithium, and n-butylmagnesium chloride were obtained from Ventron, and vinyllithium was bought from Organometallics. Allyllithium was prepared from allyltriphenyltin.36 Ethyllithium was prepared from ethyl chloride (Matheson), and n-propyllithium from n-propyl chloride, both as described below. All lithium reagents were titrated by the method of Watson and Eastham.% n-Butylcyclohexane was obtained from Aldrich, n-butylcyclopentane from Sigma, 4methylnonane and 4-methyldecane from Pfaltz and Bauer, and 2-methyloctane and 3-methylnonane from Fluka. An authentic sample of 3-methyl-l-nonene was prepared via displacement of (35) Seyferth, D.; Weiner, M. A. J. Org. Chem. 1961,26,4797. (36)Watson, S.C.; Eastham, J. F. J. Organomet. Chem. 1967,9,165.
Lipshutz e t al. the tusylate of 3-methylpent4-en-1-01(the alcohol being p u r c h e d from Albany International, Columbus, OH) with n-Bu2Cu(CN)Li2 in EbO (-78 0 "C) in >90% yield.37 3-Iodo-n-heptylbenzene was prepared from l-phenyl-3-heptanol by using 47% HI.% Styrene oxide and cyclopenteneoxide were obtained from Aldrich. l-tert-Butylcyclohexene oxide,39 1,l-diethylethylene oxide,40 isoprene epoxide,40 and cis-l-methyl-4-tert-butylcyclohexene oxide41were prepared by literature procedures. cis-2-Buteneoxide and cu-methylstyreneoxide were prepared as described by Kisse1.42 l-n-Propylcyclopentene oxide was obtained as discussed by T h ~ m m e l . 4 Elemental ~ analyses were performed by MicAnal, Tucson, AZ. Preparation of Ethyllithium. Lithium dispersion (30% in mineral oil, 1% sodium, 18 g, 0.77 mol) is placed in a 500-mL three-neck round-bottom flask containing a stir bar and kept under an Argon atmosphere. The lithium is washed with dry hexane (4 X 20 mL) and then 20 mL of dry hexane is added to the lithium and the temperature lowered to -5 "C. A dry ice condenser is attached and ethyl chloride (12 mL, 167 mmol), which had been previously condensed in a separate 2-neck pear flask, is diluted with 20 mL of dry hexane and added via cannula over a 3-h period to the lithium maintained at -5 "C. After addition is complete, the mixture is allowed to come to room temperature very slowly." After stirring 3 h at room temperature the slurry takes on a purplish tint. Filtration through a sintered glass funnel is achieved via cannula (maintaining an inert atmosphere). The flask is rinsed with an additional 10 mL of dry EhO. The resulting solution is colorless. The solvent is then removed by using a v a c m pump and dry ice trap. Ethyllithium is present as a clean white solid. The solvent is then replaced with 21 mL of dry EhO. Titration% indicates the solution to be 3.80 M (79.8 mmol). The ethyllithium is then stored in the freezer and used within the next few weeks. Preparation of n -Propyllithium. Lithium dispersion (30% in mineral oil, 1%Na, 14 g, 0.6-mol) was placed in a 250-mL two-neck round-bottom flask containing a stir bar, all under an Argon atmosphere. The lithium is washed with dry hexane (5 X 20 mL) followed by addition of 15 mL of dry hexane. The slurry is cooled to -10 "C and n-PrC1, distilled previously from CaH2, is placed in a pressure equalizing dropping funnel, dissolved in 30 mL dry hexane, and added slowly over 1.5 h while maintaining the pot temperature at -10 "C. After addition is complete, the reaction is warmed to room temperature and stirring is continued for 5 h. The solution becomes purplish-brown in color. Filtration via cannula through a sintered glass funnel afforded a clear solution which is titrated and stored in the refrigerator. Typical Procedure for Reagent Preparation. In a dry two-necked flask is placed CuCN. The vessel is flushed with argon and then evacuated under high vacuum, the process being repeated three times leaving the CuCN under argon. Dry T H F (1mL/ mmol CuCN) is introduced via syringe and the slurry is cooled to -78 "C. To this slowly stirring suspension is added the organolithium species (2 equiv relative to CuCN) dropwise. The heterogeneous mixture is allowed to warm gradually until complete dissolution results (may require 0 "C) and is then recooled to -78 "C (may get turbid at high concentrations). The substrate is then introduced either as a solution in THF, or as a neat liquid and stirred at the appropriate temperature until starting material is consumed. Reactions were routinely followed by TLC or VPC or both. Following completion, the reaction is quenched with a mixture composed of 10% concentrated NH40H/saturated
-
(37)Lipshutz, B. H.; Parker, D.; Kozlowski, J. A.; Miller, R. D. J. Org. Chem. 1983,48,3334. (38)Cf. Vogel, A. I. In "Practical Organic Chemistry", 4th ed.; Longman: London, 1978; pp 392-393. (39)Benkeser, R. A.; Agnihotri, R. K.; Burrow, M. L.; Kaiser, E. M.; Mallan, J. M.; Ryan, P. W. J. Org. Chem. 1964,29,1313. (40)Kovach, M.; Nielsen, D. R.; Rideout, W. H. J. Am. Chem. SOC. 1960,82,4328. (41)Murphy, D. K.; Alumbaugh, R. L.; Rickborn, B. J. Am. Chem. SOC. 1969,9i,2649. (42)Kissel, C. L. Ph.D. Thesis, UCSB, 1973. (43)Thummel, R. P. Ph.D. Thesis, UCSB, 1971. (44)Even after addition is complete and the mixture is a t ambient temperature, the reaction may suddenly become exothermic. Hence, an ice bath should be kept ready a t all times. For an alternate preparation with EtBr, see: Maaamune, S.; Choy, S. Aldrichimica Acta 1982,15,47.
Substitution Reactions with Mixed Organocuprates aqueous NH,Cl solution and allowed to stir at room temperature for 5-30 min. Standard extractive workup followed by VPC analysis, distillation, or chromatographic purification afforded the results indicated in the text. n -Butylcyclohexane. The cuprate n-BuzCu(CN)Liz was prepared from CuCN (70 mg,0.78 "01) in 1.0 mL THF, to which was added n-BuLi (0.65 mL, 1.41 mmol). The resulting solution was a tan-brown in color; however, at higher concentrations and at low temperatures (-78 "C), a cloudy, emulsion-like mixture may be observed. Cyclohexyl iodide (65 pL, 0.50 mmol) was added at -78 "C, stirred at that temperature for 1 h, and then quenched. VPC analysis indicated essentially quantitative formation of the product as determined by using tert-butylcyclohexane as an internal standard. Generation of n-BuzCu(CN)Lizin either EhO or DME, as above, provides a slightly turbid solution between -75 and 0 "C. In toluene, however, the cuprate appeared to precipitate as a brownish solid, even at 0 "C. In 1:l THF:EhO, as with 1:l THF:toluene, a pale yellow solution forms. n -Butylcyclohexane from Cyclohexyl Bromide. The cuprate n-BuzCu(CN)Lizwas prepared as described above with CuCN (92 mg, 1.02 mmol), 1.1 mL THF, and n-BuLi (0.92 mL, 1.95 "01). The bromide (62 pL, 0.50 mmol) was introduced at -78 "C, and the solution was warmed to room temperature for 6 h and then quenched. QuantitativeVPC analysis indicated 41 % product. II -Butylcyclopentane from Cyclopentyl Iodide. The cuprate was formed as above from CuCN (82 mg, 0.91 mmol), THF (1.1 mL), and n-BuLi (0.79 mL, 1.72 "01). The starting iodide (58 pL, 0.50 mmol) was added neat via syringe to the cold (-78 "C) cuprate where it was stirred for 2 h and then quenched. Analysis by VPC indicated an 82% yield of product. n -Butylcyclopentane from Cyclopentyl Bromide. The cuprate, n-BuzCu(CN)Liz,was formed as above from CuCN (86 mg, 0.96 mmol), 1.0 mL THF', and n-BuLi (0.88 mL, 1.85 mmol). To the tan solution, maintained at -78 "C, was added bromocyclopentane (54 pL, 0.50 mmol) and the solution warmed to 0 "C for 6 h and then quenched. Quantitative VPC indicated an 86% yield of product. 4-Methyloctane from 2-Iodopentane. Cuprate n-BuzCu(CN)Li2was prepared as above from CuCN (83 mg, 0.93 mmol), 1.0 mL THF, and n-BuLi (0.86 mL, 1.81 mmol). Introduction of 2-iodopentane (66 pL, 0.50 mmol) to the cold (-78 "C) solution was followed by stirring at -50 "C for 2 h and then quenching in the usual fashion. VPC analysis showed a 99% yield of the desired hydrocarbon. 4-Methyloctane from 2-Bromopentane. Preparation of n-BuzCu(CN)Lizfollowed the procedures above by using CuCN (71 mg, 0.79 mmol), 1.2 mL THF, and n-BuLi (0.73 mL, 1.53 mmol). To this solution at -78 "C was added the bromide (62 pL, 0.50 mmol), and the solution was warmed to 0 "C for 2 h and then to room temperature for 1 h and then quenched. VPC analysis showed a 94% yield of 4-methyloctane. 4-Methyldecenelqb from 2-Bromooctane. The cuprate, (allyl)zCu(CN)Liz,was formed from CuCN (101 mg, 1.13 mmol) in 1.2 mL THF, to which was added allyllithium (1.26 mL, 2.25 mmol). To this rust red solution was added 2-bromooctane (100 pL, 0.56 mmol) at -78 "C, and the solution was warmed to -22 "C for 1.5 h and then quenched. VPC analysis showed greater than 90% product. 3-Methylnonene from 2-Iodooctane. The cuprate, (vinyl)zCu(CN)Liz,was prepared from CuCN (89 mg, 1.0 mmol) in 1.0 mL of THF and vinyllithium (1.05 mL, 2.0 mmol) as a tanbrown solution. Cooling to -78 OC was followed by addition of the iodide (91 pL, 0.50 mmol) and the mixture was warmed to 0 OC for 6 h and then quenched. VPC indicated a 90% yield of product, along with ca. 6% of starting material. 2-Methyloctane from 2-Iodooctane. MezCu(CN)Lizwas prepared from CuCN (89 mg, 1.0 mmol) in 1.0 mL of THF and 1.48 mL (2.0 mmol) of MeLi (in EtzO, low halide). Cooling the cuprate to -78 OC gave a turbid, somewhat viscous reagent to After 5 min which was introduced the iodide (91 pL, 0.50 "01). at -78 "C, the mixture was warmed to 0 "C for 2 h and then quenched. VPC analysis indicated an 89% yield of product. 3-Methylnonane from 2-Iodooctane. Et&u(CN)Liz was formed from CuCN (55 mg, 0.62 mmol) in 1.3 mL of THF and
J. Org. Chem., Vol. 49, No. 21, 1984 3935 EtLi (1.12 mL, 1.16 mmol) as a light tan solution. 2-Iodooctane was added to the solution, the solution was precooled to -78 "C where stirring was continued for 1.5 h, and then the reaction was quenched. VPC indicated a quantitative yield of the desired hydrocarbon. 4-Methyldecane from 2-Iodooctane. The cuprate n-PrzCu(CN)Lizwas prepared from CuCN (43 mg,0.48 mmol) in 0.50 mL of THF and n-PrLi (0.48 mL, 0.94 mmol). The tan solution was cooled to -78 "C to which was added the iodide (46 pL, 0.25 "01) and the temperature maintained for 1 h. Quenching followed by VPC analysis showed a 90% yield of product along with 10% starting material remaining. 1-Phenyl-3-vinylheptane from 1-Phenyl-3-iodoheptane. The vinyl cuprate (vinyl)zCu(CN)Liz was prepared as above from CuCN (42 mg, 0.46 mmol) and 0.48 mL (0.92 mmol) of vinyllithium in 0.25 mL of THF. The iodide (70 mg, 0.23 mmol) in 0.3 mL of THF was added to the cold reagent (-78 "C) and then warmed to 0 "C for 7.5 h. Quenching, an extractive workup, and filtration of the crude product through SiOz (hexanes) gave 32.4 mg (70%)of a colorless oil: E t (neat) cm-' 1640; 'H NMR, 6 1.25 (12 H, m), 2.52 (2 H, m), 4.85 (1H, dd, J = 2.7 Hz), 5.0 (1 H, d, J = 1 Hz), 5.55 (1 H, m), 7.15 (5 H, a, br); mass spectrum, m/e (relative intensity) 202 (M+, 4.7), 160 (4.0), 145 (4.7), 131 (4.7), 118 (3.4), 117 (8.1),105 (34.9), 104 (100);high-resolution MS, calcd for Cl6HZ2202.1720, found 202.1728. 3-Methylnonane from (R)-(-)-2-Iodooctane. The cuprate, EgCu(CN)Liz,was prepared as above from CuCN (2.0 g, 22.3 mmol), 37 mL of THF, and EtLi (8.3 mL, 44.2 mmol). To the cold (-96 "C) solution was added the chiral iodide (2.7 mL, 14.9 mmol, 87% optically pure) and the solution was stirred at this temperature for 25 min. Warming to -78 "C for 1.5 h was followed by quenching (slowly!), extractive workup (EhO), and isolation by di~tillation."~A rotation on neat material of 99+% (VPC) purity indicated at most 1.1-1.2% inversion had occurred. 3-Methylnonane from (R)-(-)-2-Iodooctane via EtzCuLi. The lower order cuprate was formed from CUI (1.6 g, 8.6 mmol) in 9 mL of THF to which was added EtLi (6.8 mL, 17.0 mmol). The cuprate was cooled to -78 O C where the iodide (0.73 mL, 4.0 mmol, 86% optically pure) was added, followed by warming to -50 "C for 3 h, and was then quenched at this temperature. Workup, isolation by di~tillation,'~~ and then preparative VPC (2 m, 10% Apiezon N on Chromosorb W, 60/80 mesh) gave material of >99% purity, which gave no rotation. 3-Methylnonane from (S)-(+)-2-Bromooctane. The mixed cuprate Et(Me)Cu(CN)Lizwas formed from CuCN (2.72 g, 30.3 "01) in 25 mL of THF, to which was added at -78 "C MeLi (19.1 mL, 30.2 "01) and EtLi (10.90mL, 30.2 mmol), and the mixture was warmed until a brownish solution resulted (usually
