A Potential Textbook Addition

Figure 1. Catalytic asymmetric allylic alkylation. Taken from Ref. [1]

The article of the week concerns a type of reaction which may be familiar to students of Organic Chemistry – the reaction of a cuprate (R2CuLi).

It is beyond doubt that organolithiums and Grignard Reagents are very useful reagents in synthesis, as they enable the formation of carbon-carbon bonds. Yet these textbook reactions suffer from strong reactivitives of the organometallics – the stronger and more basic these reagents are, the less controllable and selective the reaction outcome will be. For course, this long-standing issue has stimulated the developments of better methods to generate C-C bonds.

One of the interesting effects of adding a Cu(I) salt to these reagents is that it changes the chemical behaviors of the resultant reagents. While Organolithiums and Grignards are seen as hard reagents, cuprates (R2CuLi) are soft reagents which undergo Michael and SN2’ reactions.

While Grignard reagents can be switched to a soft reagent by a catalytic amount of Cu (I), the hallmark of an organolithium-derived cuprate is that its generation is a stoichiometric process. The stoichiometry is of great importance here – 2 equivalents of RLi reacts with 1 equivalent of copper (I) salt to afford R2CuLi (Li: Cu = 2:1). If the ratio is 1:1, the reagent is called an ‘organocopper’ reagent (e.g. MeCu.LiI), which is selective for certain substrates. Because of this, a catalytic protocol of the generation of cuprates from organolithiums should be a fascinating one.


Figure 2. Ligand screening. L4, L5, and L6 prove to be advantageous ligands. Taken from Ref. [1]

Professor Ben Feringa and his group has got a nice publication on Nature Chemistry this week, which nicely demonstrated the catalytic version discussed above (Figure 2) [1]. The reaction they have investigated is designated as an allylic alkylation. Using the allylic halides, they carried out allylic alkylations with the cuprates generated under catalytic amount of Cu(I), from the organolithiums. By employing phosphoramidite or the TaniaPhos ligands, they could achieve the asymmetric allylic alkylation, with the major product being the SN2’ product (rather than the completing SN2 product) with impressive e.e.


Figure 3. The investigation of the mechanism. Probing the active copper species. Taken from Ref. [1].

They have also carried out NMR studies to probe the chemical species involved in the reaction (Figure 3). They found that the diphosphine copper monoalkyl species (e.g. TaniaPhos-CuMe , compound A in Figure 3) was the active species responsible for the allylic alkylation at -80ºC, and they have verified this proposal via additional control experiments. They have also shown that the use of ether as a solvent will lead to detrimental effects on the reaction (due to the formation of species B in Figure 3). The best solvent for the catalytic reaction is dichlorometahane.

A nice addition to the list of textbook reactions in the near future!

References:

1. Catalytic asymmetric carbon–carbon bond formation via allylic alkylations with organolithium compounds
Manuel Perez, Martın Fanana´s-Mastral, Pieter H. Bos, Alena Rudolph, Syuzanna R. Harutyunyan and Ben L. Feringa
Nature Chemistry
13th March, 2011
DOI: 10.1038/NCHEM.1009