Download Enantiospecific skeleton expanding cross

Enantiospecific skeleton expanding
cross-coupling reaction
Skeleton expanding reactions of triflate modified αhydroxy carbonyl compounds as an alternative to
enolate alkylation reactions
Albert-Ludwigs-Universität Freiburg
Technology
This reaction technology provides a cost effective, highly enantiospecific (>99% ee) chemical reaction
pathway for the modification and expansion of α-hydroxy carbonyls, which are themselves readily available from the chiral pool. Grignard reagents possessing a range of potential substituents are reacted
under mild conditions with a triflate modified carbonyl at the α-carbon to bind a wide range of substituents with consequent chiral inversion at the α-carbon. Widely available Grignard reagents combined
with an extremely cheap ZnCl2 catalyst, and high enantiospecificity render this reaction ideal for low
cost organic synthesis. In just one example, a lactic acid derivative is converted to 2-methylhexanoic
acid with excellent yield. This compound is an important building block in the production of the potential
high-potency sweetener NC-00637. Ultimately, this new reaction presents an extremely attractive alternative to enolate alkylation.
Innovation
ƒ Highly enantiospecific carbon-carbon cross-coupling reaction
ƒ Inexpensive and non-toxic anhydrous zinc chloride catalyst
ƒ Reaction does not require the use of expensive chiral ligands or
auxiliaries
ƒ Reaction occurs under mild conditions (-20 – 20 °C)
ƒ Large variations in the substrate molecule and reacting Grignard
reagent are accommodated by the zinc-catalyzed reaction
ƒ Products can be recovered with ease through fractional distillation
Application
Responsible
Scientist
Prof. Dr. Breit
Institute of Organic
Chemistry and Biochemistry
Branch
Pharmaceutical and Chemical
Industries
Patent Status
ƒ Substitution for enolate alkylation reactions in organic synthesis
ƒ Manufacture of optically active α-alkylcarbonyl compounds on a large
scale
ƒ Alpha amino acids available from the chiral pool can be converted to
the corresponding α-hydroxyester with retention of stereo information
and employed in the reaction
Patent granted.:
US 8212065
EP 2190809 (B1) in DE, FR,
GB, CH, NL
Market Potential
ZEE20070628
ƒ Replacement of costly, and low enantiospecific alkylation reactions
in the chemical and pharmaceutical industries
ƒ E.g. - Asymmetric α-alkylated mandelic acids derivatives used as
chiral auxiliaries, chiral catalysts, and optical resolution reagents
Contact
Campus Technologies Freiburg GmbH | Stefan-Meier-Str. 8 | D-79104 Freiburg
Email: [email protected]
Tel: +49 (0)761 203-4987
Fax:+49 (0)761 203-5021
Filed (PRD) Sep 24th 2007
Reference Number
Status: Dez-12