[7440-23-5]  · Na  · Sodium  · (MW 22.99)

(powerful one-electron reducing agent for most functional groups;1 reductively couples ketones and esters to unsaturated carbon atoms;2 reductively eliminates and couples halogens and other groups; can be used to generate alkoxides)

Physical Data: mp 97.8 °C; d 0.968 g cm-3.

Solubility: sol liquid NH3; slightly sol ethereal solvents; dec in alcohols; reacts violently in H2O.

Form Supplied in: silver-white or gray solid in brick, stick, or ingot form; more commonly as 3-8 mm spheres or as a dispersion in various inert oils.

Purification: surface oxide can be removed by heating in toluene;3 oxide impurities can usually be ignored.

Handling, Storage, and Precautions: the dry solid quickly oxidizes when exposed to air and in very moist air is potentially flammable. The highly corrosive sodium vapor ignites spontaneously in air, and is a severe irritant to eyes, skin, and mucous membranes. Utmost care should be taken to keep sodium away from halogenated solvents, oxidants, and aqueous mineral acids. Fires should be quenched with a dry powder such as Na2CO3, NaCl, or NaF; water, CO2, Halon, and silica gel should be avoided. Excess sodium is best disposed of by slow introduction into a flask of isopropanol, possibly containing 1% water, taking care to vent liberated H2, and neutralizing the resulting solution with aqueous acid. Sodium stored under oil is best weighed by rinsing freshly cut pieces with hexane and after evaporation adding to a tared beaker containing hexane.

Reaction Conditions.

Sodium, along with the other commonly used alkali metals Lithium and Potassium, is an extremely powerful one-electron reductant. Historically, solutions of sodium in ammonia have been used to reduce a wide variety of functional groups (see also Sodium-Ammonia for some of these transformations, particularly the Birch reduction of aromatic rings).4 These reductions are usually carried out in the presence of proton donors, normally simple alcohols or NH4Cl, though occasionally these are added prior to workup. Many reductions are performed with solutions of sodium in refluxing alcohols; here a large excess of sodium is often required due to its gradual decomposition to alkoxides and H2. It is sometimes simpler to add a mixture of alcohol and substrate to a dispersion of sodium in an inert solvent such as toluene. HMPA is also occasionally employed as a solvent;5 solutions of sodium in HMPA behave similarly to those in ammonia.6 While sodium is insoluble in solvents such as DME or THF, naphthalene is usually included, and a green solution of the Sodium Naphthalenide radical anion forms.7 Though the reduction potential of this system is similar to that of sodium in other solvents (a half-wave potential of -2.5 V8 vs. -2.96 V in HMPA6b and -2.59 V in NH31b), side reactions are often minimized, and reductions are sometimes titrated to color end-point. Other additives such as anthracene and benzophenone result in solutions with decreased, more selective, reducing power, though this has been rarely exploited.8

Reduction of Unsaturated Bonds.

The classical reduction of ketones with sodium in alcohol, along with the mechanistically similar reduction in ammonia with added proton donors, still finds use in certain systems where the desired stereochemistry cannot be generated by metal hydrides (see also Lithium).1d-g The ammonia system is preferred, minimizing epimerization of ketones and equilibration of product alcohols. NH4Cl has been recommended as proton donor to suppress hydrogen transfer,9 though this requires a large excess of sodium;10 using several equivalents of a primary alcohol also minimizes this side reaction.11 Alcohols, ethers, amines, carboxylic acids, and isolated internal double bonds are unaffected, but most other functional groups have reduction potentials less negative than aliphatic ketones. Aromatic ketones and a-heteroatom-substituted ketones are generally unsuitable substrates for these reductions.

Reductions are kinetically controlled, though the literature contains several mistaken assumptions on this point; stereochemistry is determined by pyramidalization of the ketyl and subsequent carbanion intermediates, and prediction of the stereochemical result is in most cases extremely difficult. Study of certain systems does allow a few general remarks to be made. Unhindered cyclohexanones usually give larger equatorial:axial ratios than can be obtained with metal hydrides or by equilibration.12 Generation of equatorial alcohols from hindered cyclohexanones often requires the use of dissolving metals, while metal hydrides can give exclusively the axial product (eqs 1 and 2).13 Bicyclo[2.2.1]heptan-2-ones always provide an excess of the endo-alcohol (eq 3).14,15

Imines are reduced to amines in good yield by sodium in alcohols, probably through a similar mechanism. In the absence of proton donors, reductive dimerization dominates.16 1,3-Diimines, which exist as tautomeric enamino imine mixtures, are reduced to diastereomeric mixtures of diamines (eq 4).17 Allylic imines have been reduced to alkenes.18 Reduction of oximes by sodium in alcohol is particularly useful,19 since Lithium Aluminum Hydride can produce Beckmann rearrangements or aziridines.20,21 Bicyclo[2.2.1]heptan-2-one and tricyclo[,6]heptan-3-one oxime reductions yield predominantly endo-amines (eq 5).21,22

The reduction of esters to alcohols with sodium in alcohol (Bouveault-Blanc reduction)23 has been all but supplanted by the use of metal hydrides. Where an ester must be reduced in the presence of an acid, an improved procedure run in ammonia can be used effectively (eq 6).24

Dissolving metal reductions of a,b-unsaturated carbonyl compounds are almost always performed with lithium in ammonia (see Lithium),1d though sodium is occasionally used without any particular change in result. Selected examples of enone reduction with sodium in HMPA have been examined;6b,25 these are most notable for the fact that they tend to produce product mixtures enriched in the less stable epimer, compared to reactions run in ammonia (eq 7).25a,1e

The reduction of internal acyclic alkynes to trans-alkenes by sodium in ammonia is well known.1b Complications in reducing terminal alkynes result from deprotonation by NaNH2, formed in situ. This can be exploited by addition of an equivalent of NaNH2,26 or overcome by addition of ammonium salts.27 Medium-ring cyclic alkynes often give mixtures of cis- and trans-alkenes, resulting from partial isomerization by NaNH2 to allenes,28 which in turn give cis/trans mixtures dependent on product stability and the presence or absence of proton donors.29 Sodium in HMPA/t-BuOH has been shown to reduce alkynes;30 internal monoalkenes, inert under most conditions, give near-equilibrium mixtures of alkanes with this system (eqs 8 and 9).31 Conjugated dienes are reduced via a cis-radical anion,32 while, with lithium, trans-dianions may play a role. Dimerization and regioisomer formation usually preclude the use of sodium, though exceptions exist.33 A few reports of homoconjugated diene reduction have appeared.34

Pinacol Coupling Reactions.

In the absence of proton donors, reductions of carbonyl compounds often lead to significant amounts of reductively coupled products, but the intentional pinacol coupling of ketones with sodium in inert solvents is typically a low-yielding, unselective process. Milder conditions utilize lanthanoids and low-valent transition metals, particularly titanium.35 Sodium is used only in cases where no other functional groups are present.36 Sodium is often employed in related intramolecular couplings with unsaturated carbon-carbon bonds, forming five- and six-membered rings regio- and (often) stereoselectively.37 Ketyls cyclize onto allylic systems with anti displacement (eqs 10 and 11).38 Transannular cyclizations have also been demonstrated.39 Alkynes are cyclized similarly (eq 12),40 usually with Sodium Naphthalenide.41 With allenes, the exo closure product is obtained (eq 13),42 though prolonged reaction can scramble the position of the resulting double bond.43

Acyloin Couplings.

Reductions of esters under aprotic conditions, usually refluxing toluene or xylene, result in a-hydroxy ketones, also called acyloins.2 Sodium-Potassium Alloy alloy is also used and allows reaction at lower temperatures. Rigorous exclusion of oxygen during reaction and workup is essential. Base-catalyzed side reactions are suppressed by the coaddition of substrate and Chlorotrimethylsilane, so as to trap the enediolate and alkoxide products, though good yields can sometimes be obtained regardless.2,44 Workup is greatly simplified, and the acyloins can be freed by treatment with aqueous acid or deoxygenated methanol. Couplings can be performed on esters with leaving groups at the b-position (eq 14),45 resulting in a useful cyclopropanone hemiacetal synthesis (eq 15).46

Intramolecular acyloin couplings are an enormously successful method for forming four-membered rings.47 Highly strained products can undergo subsequent thermal ring opening (eq 16); Na/K is sometimes more effective in these cases. Hindered diesters can undergo a,a-bond cleavage prior to reduction.2 Five- and six-membered rings are routinely generated, often without employing TMSCl. Larger rings, more difficult to form by other methods, are also closed in good yields,48 including several polycyclic frameworks (eq 17).49 Rings containing 12, 24, and 42 carbon atoms,50 paracyclophanes, and rings containing N, O, S, and Si atoms have been formed.51

Reduction of Saturated Bonds.

Typical Birch reduction conditions dehalogenate aryl, vinyl, bridgehead, and cyclopropyl halides, though side reactions are often troublesome.52 Alkyl fluorides are not reduced by sodium under any conditions, requiring a K/crown ether system.53 Sodium in alcohol/THF is an effective substitute for Birch conditions;54,55 these conditions can also reduce simple alkyl halides (eq 18).36b A simpler procedure employing refluxing ethanol is superior in some cases (eq 19).56

Alcohols are usually derivatized and reduced with metal hydrides, though other methods have received attention.57 Among dissolving metal techniques, lithium or potassium in amines are most often used to hydrogenolyze various esters. Sodium in HMPA gives nearly quantitative yields of alkanes from tertiary esters.58 Sodium in ammonia can cleave alkyl mesylates (eq 20),59 while phosphate esters or mesylates of phenols are similarly reduced to aromatic hydrocarbons.60 Like metal hydrides, sodium in ammonia cleaves epoxides to give the more substituted alcohols, with the exception of aryl-substituted epoxides (eq 21).61 Lithium and second-row metals, particularly calcium, are also effective for epoxide cleavages.

Most other aliphatic ethers are inert to dissolving metals, but benzyl ethers (as well as esters, amines, and thioethers) are readily debenzylated by sodium in ammonia. This is a common deprotection method in peptide and carbohydrate chemistry.62 Substituted trityl ethers have been used to protect hydroxyl groups in nucleotides. The differing reduction potentials for the p-methoxytrityl63 and a-naphthyldiphenylmethyl64 groups allow for selective deprotection using sodium/aromatic hydrocarbon systems (eqs 22 and 23). Simple phenyl ethers are cleaved by sodium only with great difficulty.

While many desulfurizations by alkali metals are known,65 use of sodium is generally restricted to alkyl aryl thioethers. These are cleaved in the presence of aryl ethers by sodium in HMPA.66 Phenyl thioethers are more often cleaved in refluxing alcohols (eq 24).67 By substituting TMSCl for the proton source, alkyl or vinyl silanes can be isolated (eq 25).68 Sodium in ammonia has been used in a deoxy sugar synthesis where more typical reagents (Raney Nickel, Nickel Boride, Tri-n-butylstannane) fail.69

Sulfones are hydrogenolyzed by sodium in ethanol.70 This method is again most often used where commonly preferred methods fail (eq 26),71 and includes a rare application to an a-substituted carboxylic acid (eq 27).72 Aryl sulfonamides are readily cleaved to amines with sodium naphthalenide and Sodium Anthracenide.73 Tosylates74,62 and N-tosylsulfoximines75 are similarly reduced to alcohols and sulfoximines, respectively.

Reductive decyanation is effectively performed with sodium in ammonia.76 This method complements Sodium Borohydride, which is sometimes ineffective with a-amino nitrile substrates and provides products with inversion of configuration (eq 28).77 An alternative method employing sodium or preferably potassium in HMPA/t-BuOH also smoothly removes nitriles.78 Isocyanides are reduced to hydrocarbons, providing an effective deamination method (eq 29).79 Rearrangements are largely avoided but, with acyclic substrates, loss of optical activity results. Finally, one last common application of the sodium/ammonia system is the reductive cleavage of acylated N-N bonds (eq 30).80

Reductive Eliminations.

When a leaving group is situated adjacent to a reducible functionality, elimination results. It is generally agreed that at the site of the initially reduced carbon atom, an anion is generated which then displaces the leaving group. Highly strained alkenes have been generated in this way. Usually vic-dihalides are the immediate precursor (eq 31),81 though vic-dimesylates have also been used.82 Alkenes have also been generated from vic-dinitriles83 and more exotic combinations of functional groups.84 Fragmentations of b-chloro ethers,85 b,g-epoxy nitriles,86 and b-hydroxy nitriles87 have also been demonstrated, the last undergoing subsequent double bond reduction (eqs 32-34).

Wurtz Reaction.

The classical intermolecular coupling of halides with sodium, mechanistically related to the eliminations noted above, is of limited use. Cross couplings lead to mixtures of desired and homocoupled products, while dimerizations are of little synthetic value. Magnesium, lithium, and copper reagents are normally employed here.88 Intramolecular couplings frequently employ sodium, however. Ring closure to form [2.2]phanes is effective when tetraphenylethylene (TPE) is used catalytically (eq 35).89 Greatest utility is found in the formation of cyclopropanes (eq 36),90 and to a lesser extent cyclobutanes (eq 37),91 where Zinc is preferred.

Use as a Base.

Sodium reacts slowly with alcohols to give solutions of alkoxides. While sodium alkoxides are far more commonly generated by Sodium Hydride, or obtained commercially, the older method is still occasionally used. The protic Bamford-Stevens reaction uses sodium to generate alkoxides from Ethylene Glycol, present as solvent.92 Sodium methoxide can be substituted, but the original conditions are usually employed. Regioselectivity can be a problem; while the more substituted regioisomer usually predominates, prediction is difficult.93 Rearrangements of cationic intermediates also limit its use, though many successful examples of this reaction do exist (eq 38).94

Related Reagents.

Sodium-Alcohol; Sodium-Alumina; Sodium-Ammonia.

1. (a) House, H. O. Modern Synthetic Reactions; Benjamin: Menlo Park, CA, 1972. (b) Smith, M. In Reduction: Techniques and Applications in Organic Synthesis; Augustine, R. L., Ed.; Dekker: New York, 1968. (c) Hudlicky, M. Reductions in Organic Chemistry; Horwood: Chichester, 1984. (d) Caine, D. OR 1976, 23, 1. (e) Pradhan, S. K. T 1986, 42, 6351. (f) Huffman, J. W. ACR 1983, 16, 398. (g) Huffman, J. W. COS 1991, 8, Chapter 1.4.
2. (a) Finley, K. T. CR 1964, 64, 573. (b) Bloomfield, J. J.; Owsley, D. C.; Nelke, J. M. OR 1976, 23, 259.
3. Fieser, M.; Fieser, L. F. FF 1967, 1, 1022.
4. The Chemistry of Non-Aqueous Solvents; Lagowski, J. J., Ed.; Academic: New York, 1967; Vol. 2, Chapter 6,7.
5. Normant, H. AG(E) 1967, 6, 1046.
6. (a) Schindewolf, U. AG(E) 1968, 7, 190. (b) Bowers, K. W.; Giese, R. W.; Grimshaw, J.; House, H. O.; Kolodny, N. H.; Kronberger, K.; Roe, D. K. JACS 1970, 92, 2783.
7. Garst, J. F. ACR 1971, 4, 400.
8. Mann, C. K.; Barnes, K. K. Electrochemical Reactions in Non-Aqueous Systems; Dekker: New York, 1970.
9. Rautenstrauch, V.; Willhalm, B.; Thommen, W.; Burger, U. HCA 1981, 64, 2109.
10. Grieco, P. A.; Burke, S.; Metz, W.; Nishizawa, M. JOC 1979, 44, 152.
11. Huffman, J. W.; Copley, D. J. JOC 1977, 42, 3811.
12. (a) Huffman, J. W.; Charles, J. T. JACS 1968, 90, 6486. (b) Solodar, J. JOC 1976, 41, 3461.
13. (a) Giroud, A. M.; Rassat, A. BSF 1976, 1881. (b) Aranda, G.; Bernassau, J.-M.; Fetizon, M.; Hanna, I. JOC 1985, 50, 1156.
14. Barton, D. H. R.; Werstiuk, W. H. JCS(C) 1968, 148.
15. (a) Welch, S. C.; Walters, R. L. SC 1973, 3, 419. (b) Rautenstrauch, V. CC 1986, 1558.
16. (a) Smith, J. G.; Ho, I. JOC 1972, 37, 653. (b) Jaunin, R.; Magnenat, J.-P. HCA 1959, 42, 328.
17. Barluenga, J.; Olano, B.; Fustero, S. JOC 1983, 48, 2255.
18. Barbulescu, N.; Cuza, O.; Barbulescu, E.; Moya-Gheorghe, S.; Zavoranu, D. RRC 1985, 36, 295 (CA 1985, 103, 123 042t).
19. Lycan, W. H.; Puntambeker, S. V.; Marvel, C. S. OSC 1943, 2, 318.
20. Chen, S.-C. S 1974, 691.
21. Ordubadi, M. D.; Pekhk, T. I.; Belikova, N. A.; Rakhmanchik, T. M.; Platé, A. F. JOU 1984, 20, 678.
22. Daniel, A.; Pavia, A. A. BSF 1971, 1060.
23. (a) Ford, S. G.; Marvel, C. S. OSC 1943, 2, 372. (b) Adkins, H.; Gillespie, R. H. OSC 1955, 3, 671.
24. Paquette, L. A.; Nelson, N. A. JOC 1962, 27, 2272.
25. (a) House, H. O.; Giese, R. W.; Kronberger, K.; Kaplan, J. P.; Simeone, J. F. JACS 1970, 92, 2800. (b) Argibeaud, P.; Larchevêque, M.; Normant, H.; Tchoubar, B. BSF 1968, 595.
26. Dobson, N. A.; Raphael, R. A. JCS 1955, 3558.
27. Henne, A. L.; Greenlee, K. W. JACS 1943, 65, 2020.
28. Svoboda, M.; Sicher, J.; Závada, J. TL 1964, 15.
29. Vaidyanathaswamy, R.; Joshi, G. C.; Devaprabhakara, D. TL 1971, 2075.
30. House, H. O.; Kinloch, E. F. JOC 1974, 39, 747.
31. Whitesides, G. M.; Ehmann, W. J. JOC 1970, 35, 3565.
32. Weyenberg, D. R.; Toporcer, L. H.; Nelson, L. E. JOC 1968, 33, 1975.
33. (a) Loev, B.; Dawson, C. R. JACS 1956, 78, 1180. (b) Barton, D. H. R.; Lusinchi, X.; Magdzinski, L.; Ramirez, J. S. CC 1984, 1236.
34. (a) Butler, D. N. SC 1977, 7, 441. (b) Boland, W.; Hansen, V.; Jaenicke, L. S 1979, 114.
35. Robertson, G. M. COS 1991, 3, Chapter 2.6.
36. (a) Wynberg, H.; Boelema, E.; Wieringa, J. H.; Strating, J. TL 1970, 3613. (b) Nelsen, S. F.; Kapp, D. L. JACS 1986, 108, 1265.
37. (a) Hart, D. J. Science 1984, 223, 883. (b) Ramaiah, M. T 1987, 43, 3541.
38. Bertrand, M.; Teisseire, P.; Pélerin, G. NJC 1983, 7, 61.
39. (a) Jadhav, P. K.; Nayak, U. R. IJC(B) 1978, 16, 1047. (b) Eakin, M.; Martin, J.; Parker, W. CC 1965, 206.
40. Jung, M. E.; Hatfield, G. L. TL 1983, 3175.
41. (a) Pattenden, G.; Teague, S. J. JCS(P1) 1988, 1077. (b) Pradhan, S. K.; Kadam, S. R.; Kolhe, J. N.; Radhakrishnan, T. V.; Sohani, S. V.; Thaker, V. B. JOC 1981, 46, 2622. (c) Mehta, G.; Krishnamurthy, N. TL 1987, 5945.
42. Pattenden, G.; Robertson, G. M. T 1985, 41, 4001.
43. Crandall, J. K.; Mualla, M. TL 1986, 2243.
44. Snell, J. M.; McElvain, S. M. OSC 1943, 2, 114.
45. Rühlmann, K. S 1971, 236.
46. Salaün, J.; Marguerite, J. OSC 1990, 7, 131.
47. Bloomfield, J. J.; Nelke, J. M. OSC 1988, 6, 167.
48. Bloomfield, J. J.; Owsley, D. C.; Ainsworth, C.; Robertson, R. E. JOC 1975, 40, 393.
49. Bartetzko, R.; Gleiter, R.; Muthard, J. L.; Paquette, L. A. JACS 1978, 100, 5589.
50. (a) Natrajan, A.; Ferrara, J. D.; Youngs, W. J.; Sukenik, C. N., JACS 1987, 109, 7477. (b) Ashkenazi, P.; Kettenring, J.; Migdal, S.; Gutman, A. L.; Ginsburg, D. HCA 1985, 68, 2033.
51. (a) Wu, G.-S.; Martinelli, L. C.; Blanton, C. D., Jr.; Cox, R. H. JHC 1977, 14, 11. (b) Johnson, P. Y.; Kerkman, D. J. JOC 1976, 41, 1768.
52. Vogel, E.; Roth, H. D. AG(E) 1964, 3, 228.
53. Ohsawa, T.; Takagaki, T.; Haneda, A.; Oishi, T. TL 1981, 2583.
54. (a) Gassman, P. G.; Pape, P. G. JOC 1964, 29, 160. (b) Gassman, P. G.; Marshall, J. L. OSC 1973, 5, 424.
55. (a) Chou, T. C.; Chuang, K.-S.; Lin, C.-T. JOC 1988, 53, 5168. (b) Hales, N. J.; Heaney, H.; Hollinshead, J. H. S 1975, 707. (c) Hales, N. J.; Heaney, H.; Hollinshead, J. H.; Singh, P. OSC 1988, 6, 82.
56. Lap, B. V.; Paddon-Row, M. N. JOC 1979, 44, 4979.
57. Hartwig, W. T 1983, 39, 2609.
58. Deshayes, H.; Pete, J.-P. CC 1978, 567.
59. Tsuchiya, T.; Nakamura, F.; Umezawa, S. TL 1979, 2805.
60. (a) Rossi, R. A.; Bunnett, J. F. JOC 1973, 38, 2314. (b) Carnahan, J. C., Jr.; Closson, W. D.; Ganson, J. R.; Juckett, D. A.; Quaal, K. S. JACS 1976, 98, 2526.
61. Kaiser, E. M.; Edmonds, C. G.; Grubb, S. D.; Smith, J. W.; Tramp, D. JOC 1971, 36, 330.
62. Schön, I. CR 1984, 84, 287.
63. (a) Greene, G. L.; Letsinger, R. L. TL 1975, 2081. (b) Letsinger, R. L.; Lunsford, W. B. JACS 1976, 98, 3655.
64. Letsinger, R. L.; Finnan, J. L. JACS 1975, 97, 7197.
65. Block, E.; Aslam, M. T 1988, 44, 281.
66. Tiecco, M. S 1988, 749.
67. (a) Kodama, M.; Takahashi, T.; Kojima, T.; Ito, S. TL 1982, 3397. (b) Hashimoto, M.; Kan, T.; Yanagiya, M.; Shirahama, H.; Matsumoto, T. TL 1987, 5665. (c) Purrington, S. T.; Pittman, J. H. TL 1988, 6851.
68. (a) Kuwajima, I.; Kato, M.; Sato, T. CC 1978, 478. (b) Kuwajima, I.; Abe, T.; Atsumi, K. CL 1978, 383. (c) Atsumi, K.; Kuwajima, I. CL 1978, 387.
69. Haskell, T. H.; Woo, P. W. K.; Watson, D. R. JOC 1977, 42, 1302.
70. (a) Masaki, Y.; Serizawa, Y.; Nagata, K.; Kaji, K. CL 1984, 2105. (b) Kozikowski, A. P.; Mugrage, B. B.; Li, C. S.; Felder, L. TL 1986, 4817.
71. (a) Fujita, Y.; Ishiguro, M.; Onishi, T.; Nishida, T. BCJ 1982, 55, 1325. (b) Chan, T. H.; Labrecque, D. TL 1991, 1149.
72. Kuo, Y.-C.; Aoyama, T.; Shioiri, T. CPB 1982, 30, 2787.
73. (a) Closson, W. D.; Ji, S.; Schulenberg, S. JACS 1970, 92, 650. (b) Quaal, K. S.; Ji, S.; Kim, Y. M.; Closson, W. D.; Zubieta, J. A. JOC 1978, 43, 1311.
74. Closson, W. D.; Wriede, P.; Bank, S. JACS 1966, 88, 1581.
75. Johnson, C. R.; Lavergne, O. JOC 1989, 54, 986.
76. Tomioka, K.; Koga, K.; Yamada, S. CPB 1977, 25, 2689.
77. Bonin, M.; Romero, J. R.; Grierson, D. S.; Husson, H.-P. TL 1982, 3369.
78. Debal, A.; Cuvigny, T.; Larchevéque, M. S 1976, 391.
79. Niznik, G. E.; Walborsky, H. M. JOC 1978, 43, 2396.
80. (a) Meng, Q.; Hesse, M. SL 1990, 148. (b) Kemp, D. S.; Sidell, M. D.; Shortridge, T. J. JOC 1979, 44, 4473.
81. (a) Sampath, V.; Lund, E. C.; Knudsen, M. J.; Olmstead, M. M.; Schore, N. E. JOC 1987, 52, 3595. (b) Greene, A. E.; Luche, M.-J.; Serra, A. A. JOC 1985, 50, 3957. (c) Allred, E. L.; Beck, B. R.; Voorhees, K. J. JOC 1974, 39, 1426.
82. Hrovat, D. A.; Miyake, F.; Trammell, G.; Gilbert, K. E.; Mitchell, J.; Clardy, J.; Borden, W. T. JACS 1987, 109, 5524.
83. De Lucchi, O.; Piccolrovazzi, N.; Licini, G.; Modena, G.; Valle, G. G 1987, 117, 401.
84. (a) Marshall, J. A.; Karas, L. J. JACS 1978, 100, 3615. (b) Nicolaou, K. C.; Sipio, W. J.; Magolda, R. L.; Claremon, D. A. CC 1979, 83.
85. (a) Martin, J. D.; Pérez, C.; Ravelo, J. L. JACS 1985, 107, 516. (b) Brooks, L. A.; Snyder, H. R. OSC 1955, 3, 698.
86. Marshall, J. A.; Hagan, C. P.; Flynn, G. A. JOC 1975, 40, 1162.
87. Kametani, T.; Nemoto, H. TL 1979, 27.
88. Billington, D. C. COS 1991, 3, Chapter 2.1.
89. Vogtle, F.; Neumann, P. S 1973, 85.
90. (a) Lampman, G. M.; Aumiller, J. C. OSC 1988, 6, 133. (b) House, H. O.; Lord, R. C.; Rao, H. S. JOC 1956, 21, 1487. (c) Friedlina, R. K.; Kamyshova, A. A.; Chukovskaya, E. T. RCR 1982, 51, 368.
91. Wiberg, K. B.; Williams, V. Z., Jr. JOC 1970, 35, 369.
92. Shapiro, R. H. OR 1976, 23, 405.
93. Gianturco, M. A.; Friedel, P.; Flanagan, V. TL 1965, 1847.
94. Piers, E.; Keziere, R. J. CJC 1969, 47, 137.

Michael D. Wendt

Abbott Laboratories, Abbott Park, IL, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.