Lombardo methylenation explained

In organic chemistry, the Lombardo methylenation is a name reaction that allows for the methylenation of carbonyl compounds with the use of Lombardo's reagent, which is a mix of zinc, dibromomethane, and titanium tetrachloride.^{[1] [2] [3] [4] [5] [6] [7]}

Applications

The Lombardo methylenation has been used in the total synthesis of tetrodotoxin^[8] and hirustene.^{[9] [10]}

Notes and References

1. Lombardo. Luciano. 1982-07-27. Methylenation of carbonyl compounds with ZnCH2Br2TiCl4. Application to gibberellins. Tetrahedron Letters. 23. 41. 4293–4296. 10.1016/S0040-4039(00)88728-6.
2. Book: Wang, Zerong. 15 September 2010. Comprehensive Organic Name Reactions and Reagents. 9780470638859. 10.1002/9780470638859.conrr397.
3. Kulinkovich. Oleg G.. Meijere. Armin de. 2000-07-21. 1,n-Dicarbanionic Titanium Intermediates from Monocarbanionic Organometallics and Their Application in Organic Synthesis. Chemical Reviews. 100. 8. 2789–2834. 10.1021/cr980046z. 11749306 .
4. Pine. Stanley H.. 2004-08-15. Carbonyl Methylenation and Alkylidenation Using Titanium-Based Reagents. Organic Reactions. 1–91. 10.1002/0471264180.or043.01. 0471264180.
5. Hartley. Richard C.. Li. Jianfeng. Main. Calver A.. McKiernan. Gordon J.. 2007-06-04. Titanium carbenoid reagents for converting carbonyl groups into alkenes. Tetrahedron. 63. 23. 4825–4864. 10.1016/j.tet.2007.03.015.
6. Organic Syntheses. Luciano Lombardo. 65. 81. 1987. 10.15227/orgsyn.065.0081. Methylenation of Carbonyl Compounds: (+)-3-Methylene-cis-p-menthane.
7. Marsden. Stephen P.. Ducept. Pascal C.. 2005. Synthesis of highly substituted allenylsilanes by alkylidenation of silylketenes. Beilstein Journal of Organic Chemistry. 1. 1. 5. 10.1186/1860-5397-1-5. 16542018. 1399453. free.
8. Hinman. Andrew. Du Bois. Justin. 2003-08-30. A Stereoselective Synthesis of (−)-Tetrodotoxin. Journal of the American Chemical Society. 125. 38. 11510–11511. 10.1021/ja0368305. 13129349.
9. Ley. Steven V.. Murray. P. John. 1982. A short syntesis of (±)-hirsutene involving the use of an organoselenium-mediated cyclization reaction. Journal of the Chemical Society, Chemical Communications. 21. 1252–1253. 10.1039/C39820001252.
10. Ley. Steven V.. Murray. P. John. Palmer. Brian D.. 1985-11-14. Total synthesis of the sesquiterpene (±)-hirsutene using an organoselenium-mediated cyclization reaction. Tetrahedron. 41. 21. 4765–4769. 10.1016/S0040-4020(01)96715-8.