Isopropylmagnesium chloride is an organometallic compound with the general formula (CH3)2HCMgCl. This highly flammable, colorless, and moisture sensitive material is the Grignard reagent derived from isopropyl chloride. It is commercially available, usually as a solution in tetrahydrofuran.
This reagent is used to prepare other Grignard reagents by transmetalation.[2] An illustrative reaction involves the generation of the Grignard reagent derived from bromo-3,5-bis(trifluoromethyl)benzene:[3]
Addition of one equivalent of LiCl to isopropylmagnesium chloride gives "Turbo Grignard" solutions, named so due to the increased rate and efficiency for transmetalation reactions.[4][5]
This reaction exploits the bulky nature of the isopropyl substituent.
Turbo-Grignard reagents
As initially reported by Knochel et al.,[7]lithium chloride, isopropylmagnesium chloride enhances the ability of isopropylmagnesium chloride toward transmetalation reactions. The more reactive species, a LiCl-iPrMgCl complex, is called a Turbo-Grignard reagent. These species are related to Turbo-Hauser bases, a family of magnesium amido compounds containing also LiCl.[8] "Turbo-Grignards", as they are often called, are aggregates with the formula [i-PrMgCl·LiCl]2. These species promote formation of aryl and heteroaryl Grignard reagents by halogen-magnesium exchange:[9]
The traditional method for generating the aryl Grignard reagent proceeds less predictably:
slow, heterogeneous: XC6H4Br + Mg → XC6H4MgBr
Furthermore, traditional routes to Grignard reagents has limited functional group compatibility, whereas the Turbo-Grignard method tolerates other halides, some ester groups, and nitriles.
^Knochel, P.; Dohle, W.; Gommermann, N.; Kneisel, F. F.; Kopp, F.; Korn, T.; Sapountzis, I.; Vu, V. A. (2003). "Highly Functionalized Organomagnesium Reagents Prepared through Halogen–Metal Exchange". Angewandte Chemie International Edition. 42 (36): 4302–4320. doi:10.1002/anie.200300579. PMID14502700.
^Johnnie L. Leazer Jr; Raymond Cvetovich (2005). "A Practical and Safe Preparation of 3,5-Bis(trifluoromethyl)acetophenone". Org. Synth. 82: 115. doi:10.15227/orgsyn.082.0115.
^W. Voskuil; J. F. Arens (1968). "Chlorodiisopropylphosphine". Org. Synth. 48: 47. doi:10.15227/orgsyn.048.0047.
^Krasovskiy, A.; Knochel, P. (2004). "A LiCl-Mediated Br/Mg Exchange Reaction for the Preparation of Functionalized Aryl- and Heteroarylmagnesium Compounds from Organic Bromides". Angew. Chem. Int. Ed.43 (25): 3333–3336. doi:10.1002/anie.200454084. PMID15213967.
^Li-Yuan Bao, Robert; Zhao, Rong; Shi, Lei (2015). "Progress and Developments in the turbo Grignard Reagent i-PrMgCl·LiCl: A Ten-Year Journey". Chemical Communications. 51 (32): 6884–6900. doi:10.1039/c4cc10194d. PMID25714498.