Mcmurry reaction

Mcmurry reaction

1. BY Dr . Gurumeet.C.Wadhawa DEPARTMENT OF CHEMISTRY K. B. P . College,Vashi,Navimumbai McMurry Coupling

2. The generation of alkene via the intra or intermolecular reductive coupling of carbonyl compounds in a Titanium mediated process known as the McMurry coupling. The reaction is a versatile strategy for carboncarbon bond formation as evidenced by the large number of natural and non-natural compounds that have been synthesized using McMurry coupling reaction as key step. The McMurry reaction originally involved the use of a mixture of TiCl and LiAlH which produces the active reagent. This 3 4 reaction is related to the pinacol coupling reaction which also proceeds by reductive coupling of carbonyl compounds.

3. In the early 1970s, the research groups of T. Mukaiyama , S. Tyrlik , and J.E. McMurry5 independently discovered that the treatment of carbonyl compounds with low- valent titanium led to olefinic coupled products. In the following years, McMurry investigated the scope and limitation of the process, and today the reductive coupling of carbonyl compounds using low- valent titanium complexes to form the corresponding alkenes is known as the McMurry coupling. The general features of this coupling reaction are:

4. 1 ) it is used most often for the homocoupling of aldehydes and ketones to afford alkenes. However, mixed coupling is feasible if one component is used in excess or one of the coupling partners is a diaryl ketone ; 2) the low- valent titanium reducing agent can be prepared in many ways but the most common is the reduction of TiCl3 with a zinc-copper couple (Zn-Cu) in DME;20 3 ) if the reaction is conducted at low temperature, the pinacol intermediate may be isolated; 4 ) at high temperature the alkenes are formed directly; 5 ) sterically hindered and/or strained olefins, which cannot be prepared by other means, are formed in high yield; 6 ) even sterically hindered tetrasubstituted alkenes can be prepared; 7 ) macrocyclization under highdilution conditions is successful for the synthesis of medium and large rings and the yields are independent of the ring size unlike in other macrocyclizations (e.g., acyloin condensation); 8 ) intramolecular reactions are the fastest for the formation of five- and six- membered rings and the formation of eight- or higher- membered rings is considerably slower ; 9 ) the reaction conditions do not tolerate the presence of easily reducible functional groups (e.g., epoxides , α- halo ketones , unprotected 1,2-diols; allylic and benzylic alcohols, quinones , halohydrins , aromatic and aliphatic nitro compounds, oximes , and sulfoxides ), but most other functional groups are compatible; 10 ) aldehydes react much faster than ketones so the coupling of two aldehydes in the presence of a ketone can be performed chemoselectively ; 11) the alkene product is formed with poor stereoselectivity , although there is a slight preference for the formation of ( E)-alkenes in intermolecular reactions; and 12 ) in the presence of a chlorosilane the McMurry reaction becomes catalytic

5. References 1. (a) McMurry , J. E.; Fleming, M. P. J. Am. Chem. Soc. 1974, 96, 4708􀀐4712. (b) McMurry , J. E. Chem. Rev. 1989, 89, 1513-1524 . (Review). 2. Hirao , T. Synlett 1999, 175-181 . 3. Sabelle , S.; Hydrio , J.; Leclerc , E.; Mioskowski , C.; Renard , P.-Y. Tetrahedron Lett . 2002, 43, 3645-3648 . 4. Williams, D. R.; Heidebrecht, R. W., Jr. J. Am. Chem. Soc. 2003, 125, 1843􀀐1850. 5. Honda, T.; Namiki , H.; Nagase, H.; Mizutani , H. Tetrahedron Lett . 2003, 44, 3035-3038 . 6. Ephritikhine , M.; Villiers, C. In Modern Carbonyl Olefination Takeda, T., Ed.; Wiley- VCH: Weinheim, Germany, 2004, 223-285 . (Review). 7. Uddin , M. J.; Rao , P. N. P.; Knaus , E. E. Synlett 2004, 1513-1516 . 8. Stuhr -Hansen, N. Tetrahedron Lett . 2005, 46, 5491-5494 . 9. Zeng , D. X.; Chen, Y. Synlett 2006, 490-492 . 10. Duan , X.-F.; Zeng , J.; Zhang, Z.-B.; Zi , G.-F. J. Org. Chem. 2007, 72, 10283-10286 . 11. Debroy , P.; Lindeman, S. V.; Rathore , R. J. Org. Chem. 2009, 74, 2080-2087 . 12. Kumar, A. S.; Nagarajan, R. Synthesis 2013, 45, 1235-1246 .