Chemical Communications Blog

Researchers from the University of Geneva have developed a transition-metal-free method for the asymmetric installation of  fluoroalkyl groups.

The Alexakis group found that the use of N-heterocyclic carbenes (2) in conjunction with Grignard reagents, enabled the highly selective synthesis of γ-functionalised products (3) from readily accessible starting materials (1). The reaction was initially performed in the presence of copper(l) salts, which afforded the desired products although regioselectivity and ee were suppressed.

A range of alkyl groups (R) could be introduced in moderate yields and very good levels of enantioselectivity (84–95%) from the corresponding Grignard reagent. Similarly, the reaction was tolerant of different aryl substituents (Ar). Exchanging the aryl component with cyclic alkyl groups did not affect the ee, however, the introduction of less bulky aliphatic groups caused enantioselectivity to plummet.

The demonstrated importance of fluoroalkyl groups in medicinal chemistry necessitates the development of new methods for the introduction of this important functional group. Alexander Alexakis and his group have developed the first asymmetric allylic alkylation reaction for the synthesis of quaternary centres containing fluoroalkyl groups; a method that may be of particular benefit to the pharmaceutical industry.

Read this HOT Chem Comm article today (free to access until the 13th of December 2012):

Formation of chiral fluoroalkyl products through copper-free enantioselective allylic alkylation catalyzed by an NHC ligand
David Grassi , Hailing Li and Alexandre Alexakis
Chem. Commun., 2012, 48, 11404-11406

Researchers from the University of British Columbia have developed a ‘head to head’ dimerisation of alkynes to provide (Z)-enynes in high yields.

The conjugated enyne products are important, both as intermediates for organic synthesis and in optoelectronics – a type of electronics that detect, source and control light. Therefore, new methods for the selective synthesis of these compounds are in demand.

Platel and Schafer have overcome regioselectivity problems often associated with alkene dimerisation.  The researchers used a readily accessible Zirconium catalyst (2) in conjunction with aniline as co-catalytic proton source.

A number of alkynes (1) were successfully dimerised to provide (Z)-enynes (3) in mostly high yields. The reaction is tolerant of a number of differentially substituted aryl compounds and also some alkyl rings.

The exclusive formation of (Z)-enynes was at odds with previously established mechanistic pathways for metal-catalysed alkyne dimerisation and led the researchers to further probe the mechanism. Complex 4 was isolated when a stoichiometric amount of aniline and complex 2 were mixed, leading the researchers to consider the validity of 4 as a catalytic intermediate. When 4 was mixed with alkyne (1) under the reaction conditions, complete conversion to (Z)-enyne (3) was observed. This result suggests that the unusual dimeric imido-bridged species is a viable intermediate in the reaction pathway.

This method represents an interesting development in catalytic and regioselective C­–C bond formation.

Read the ‘HOT’ Chem Comm article today:

Zirconium catalyzed alkyne dimerization for selective Z-enyne synthesis
Rachel H. Platel and Laurel L. Schafer
Chem. Commun., 2012, 48, 10609-10611
DOI: 10.1039/C2CC35913H