· Benzyl Iodide
· (MW 218.04)
(benzylating agent for heteroatomic functional groups and enolate anions; precursor to benzylic radicals)
Physical Data: bp 93 °C/10 mmHg; mp 24.5 °C; d 1.733 at 25 °C.
Solubility: sol alcohols, ether, and aromatic solvents.
Form Supplied in: 98% pure liquid.
Handling, Storage, and Precautions: potent lachrymator; should be handled in a fume hood.
Benzylation of Heteroatomic Functional Groups.
Benzyl iodide will react with alcohols under basic conditions to afford benzyl ethers and displays higher reactivity than other benzylating agents (see Benzyl Chloride, Benzyl Bromide, Benzyl p-Toluenesulfonate). The reagent is frequently generated in situ, for example from benzyl bromide and tetrabutylammonium iodide in THF, and is useful for benzylation of sterically hindered alcohols.1 Benzylation under less basic conditions is achieved with CsF and Bu2SnO in DMF (eq 1).2 The reagent can also be used to benzylate a phenolic hydroxyl group in the presence of silver oxide.3 A benzyl penicillanate ester was prepared from the acid and benzyl iodide in the presence of triethylamine in acetone.4 Benzylation of a thiopyrone in acetone to give the S-benzylated thiopyrylium salt has been reported.5
Benzylation of Active Methylene Compounds.
Benzyl iodide is reactive toward various enolate anions and has found use in the asymmetric benzylation of such anions. For example, the enolate derived from a chiral 1,3-oxathiolan-5-one was benzylated to afford, after hydrolysis, a benzylated thioglycolic acid derivative (eq 2).6
Chiral acylsultam enolates have been allylated with benzyl iodide with high diastereoselectivity in a route to protected amino acids.7 An amide derived from ephedrine similarly affords benzylated acids and esters, and the corresponding methyl ketones are also available via this method.8 Stereoselectivity in these reactions has been attributed to chelation of the metal by the chiral auxiliary. An enantioselective synthesis of L-[3-11C]phenylalanine was achieved through a chiral glycine derivative, where an 8-phenylmenthol ester served as the chiral auxiliary under phase transfer catalysis conditions (eq 3).9 Asymmetric benzylation of an aldehyde has also been reported using a chiral metalloenamine.10
Sulfone stabilized carbanions also react with benzyl iodide.11 This methodology has been applied to the preparation of polyenes. Likewise, formamidine stabilized carbanions allow access to a-benzylated amines with this reagent.12
The benzyl radical has been generated from benzyl iodide and shown to undergo addition to unsaturated mono-13 and dinitriles.14 The resultant nitrile-stabilized radical may be further alkylated in the presence of Allyltributylstannane (eq 4). Oxidative coupling of benzyl iodide with excess Allyl Iodide in the presence of Triethylborane and oxygen has also been reported.15
Reactions with Organometallics.
Dibenzyl ketone has been prepared in 95% yield by treatment of benzyl iodide with Tetracarbonylnickel in DMF.16
- 1. (a) Czernecki, S.; Georgoulis, C.; Provelenghiou, C. TL 1976, 3535. (b) Kanai, K.; Sakamoto, I.; Ogawa, S.; Suami, T. BCJ 1987, 60, 1529.
- 2. Nagashima, M.; Ohno, M. CL 1987, 141.
- 3. Laatsch, H. LA 1980, 1321.
- 4. Brennan, J.; Hussain, F. H. S. S 1985, 749.
- 5. King, L. C.; Ozog, F. J.; Moffat, J. JACS 1951, 73, 300.
- 6. Liu, H.-H.; Chen, E.-N.; Uang, B.-J.; Wang, S-L. TL 1990, 31, 257.
- 7. Oppolzer, W.; Rodriquez, I.; Starkmann, C.; Walther, E. TL 1990, 31, 5019.
- 8. Larcheveque, M.; Ignatova, E.; Cuvigny, T. TL 1978, 18, 3961.
- 9. Fasth, K. J.; Antoni, G.; Langstrom, B. JCS(P1) 1988, 3081.
- 10. Kogen, H.; Tomioka, K.; Hashimoto, S.; Koga, K. T 1981, 37, 3951.
- 11. (a) Ogura, K.; Yahata, N.; Fujimori, T.; Fujita, M. TL 1990, 31, 4621. (b) Yamada, S.; Ohsawa, H.; Suzuki, T.; Takayama, H. JOC 1986, 51, 4934.
- 12. Loewe, M. F.; Meyers, A. I. TL 1985, 26, 3291.
- 13. Pike, P.; Hershberger, S.; Hershberger, J. TL 1985, 26, 6289.
- 14. Mizuno, K.; Ikeda, M.; Toda, S.; Otsuji, Y. JACS 1988, 110, 1288.
- 15. Suzuki, A.; Nazawa, S.; Harada, M.; Itoh, M.; Brown, H. C.; Midland, M. M. JACS 1971, 93, 1508.
- 16. Yoshisato, E.; Tsutsumi, S. JOC, 1968, 33, 869.
William E. Bauta
Sandoz Research Institute, East Hanover, NJ, USA
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