Cu-catalyzed enantioselective allylic alkylation with organolithium reagents.
This protocol describes a method for the catalytic enantioselective synthesis of tertiary and quaternary carbon stereogenic centers, which are widely present in pharmaceutical and natural products. The method is based on the direct reaction between organolithium compounds, which are cheap, readily available and broadly used in chemical synthesis, and allylic electrophiles, using chiral copper catalysts. The methodology involves the asymmetric allylic alkylation (AAA) of allyl bromides, chlorides and ethers with organolithium compounds using catalyst systems based on Cu-Taniaphos and Cu-phosphoramidites. The protocol contains a complete description of the reaction setup, a method based on1H-NMR, gas chromatography-mass spectrometry (GC-MS) and chiral HPLC for assaying the regioselectivity and enantioselectivity of the product, and isolation, purification and characterization procedures. Six Cu-catalyzed AAA reactions between different organolithium reagents and allylic systems are detailed in the text as representative examples of these procedures. These reactions proceed within 1-10 h, depending on the nature of the allylic substrate (bromide, chloride, or ether and disubstituted or trisubstituted) or the chiral ligand used (Taniaphos or phosphoramidite). However, the entire protocol, including workup and purification, generally requires an additional 4-7 h to complete.
Stratingh Institute for Chemistry, Faculty of Mathematics and NaturalSciences, University of Groningen, Groningen, The Netherlands.
Valentín
V
Hornillos
Stratingh Institute for Chemistry, Faculty of Mathematics and NaturalSciences, University of Groningen, Groningen, The Netherlands.
Sureshbabu
S
Guduguntla
Stratingh Institute for Chemistry, Faculty of Mathematics and NaturalSciences, University of Groningen, Groningen, The Netherlands.
Martín
0000-0003-4903-0502
M
Fañanás-Mastral
Stratingh Institute for Chemistry, Faculty of Mathematics and NaturalSciences, University of Groningen, Groningen, The Netherlands.
Manuel
M
Pérez
Stratingh Institute for Chemistry, Faculty of Mathematics and NaturalSciences, University of Groningen, Groningen, The Netherlands.
Pieter H
PH
Bos
Stratingh Institute for Chemistry, Faculty of Mathematics and NaturalSciences, University of Groningen, Groningen, The Netherlands.
Alena
A
Rudolph
Stratingh Institute for Chemistry, Faculty of Mathematics and NaturalSciences, University of Groningen, Groningen, The Netherlands.
Syuzanna R
0000-0003-2411-1250
SR
Harutyunyan
Stratingh Institute for Chemistry, Faculty of Mathematics and NaturalSciences, University of Groningen, Groningen, The Netherlands.
Ben L
BL
Feringa
D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry; D008094:Lithium / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D000475:Alkenes; D007202:Indicators and Reagents; D009942:Organometallic Compounds; D003300:Copper; D008094:Lithium