382180-28-1Relevant articles and documents
Enantioselective synthesis of β-amino acids Part 13. Diastereoselective alkylation of dianions derived from chiral analogs of β-aminopropanoic acid containing the α-phenylethyl group
Gutierrez-Garcia, Victor Manuel,Reyes-Rangel, Gloria,Munoz-Muniz, Omar,Juaristi, Eusebio
, p. 4189 - 4199 (2007/10/03)
Inexpensive acryloyl chloride was converted in 91% overall yield to two derivatives of β-alanine, (R,R,R)-and (R,R,S)-6, containing two chiral auxiliaries. C-Alkylation of (R,R,R)- and (R,R,S)-6 via a dianion derivative, was performed by direct metallation with 2.2 equiv. of lithium hexamethyldisilazane (LHMDS) in THF at - 78°. C-Alkylation of (R,R,S)-6-Li2 ('matched' pair of chiral auxiliaries) afforded the mono-alkylated products 8-11 in 29-96% yield and 54-95% stereoselectivity. Employment of LiCl as an additive generally increased stereoselectivities, whereas the effect of HMPA as a cosolvent was erratic. Chemical correlation of the major diastereoisomer from the alkylation reactions with (S)-α-alkyl-β-alanine (12-15) showed that addition of the electrophile preferentially takes place on the enolate's Si-face. This conclusion is also supported by molecular-modeling studies (ab initio HF/3-21G), which indicate that the lowest-energy conformation for (R,R,S)-6-Li2 presents the more sterically hindered Re-face of the enolate. The theoretical studies also predict a determining role for N-Li-O chelation in (R,R,S)-6-Li2, giving rise to an interesting 'ion-triplet' configuration for the dilithium dianion.
