title: Stereoretentive formylation of (S)-proline: new application of the self-regeneration of stereo-centres (SRS) principle via chelation to cobalt(III).
abstract: In a Vilsmeier-Haack-type formylation reaction the α-(dihydroxymethyl)-(S)-prolinato complex (+)578-p-[Co(tren){(RC,SN)-Pro[CH(OH)2]O}]Cl2·2H2O (22) was produced stereoselectively (85% ee) from the (S)-prolinato complex, (+)578-p-[Co(tren){(SC,SN)-ProO}]2(H3O)2(HOEt2)(O3SCF3)7 (18). Similar reaction of the (S)-alaninato complex, (-)578-p-[Co(tren)(S-AlaO)](H3O)(O3SCF3)3 (13), produced the racemate, rac-p-[Co(tren)(Ala{CH(OH)2}O)]SO4·2H2O (17). The contrasting stereochemical outcomes of the formylation reaction with 18versus13 were ascribed to the stereogenic character of the coordinated sec. amine of the (S)-prolinate chelate in 18, which serves to uphold a chiral environment during reaction, whereas reaction intermediates derived from 13 lack this stereochemical feature. The stereoselective formylation of (S)-proline, relying on coordination to an inert metal centre, as conducted here, constitutes a novel application of the concept of Self-Regeneration of Stereocentres (SRS). The α-(hydroxymethyl)-(S)-prolinato complex, (+)578-p-[Co(tren){(RC,SN)-Pro(CH2OH)O}]Cl2·2H2O (23) resulted from borohydride reduction of 22. The molecular structures of (+)578-p-[Co(tren){(RC,SN)-Pro[CH(OH)2]O}]Cl2·2H2O (22), rac-p-[Co(tren)-(Ala{CH(OH)2}O)]I2·H2O (17) and (+)578-p-[Co(tren){(RC,SN)-Pro(CH2OH)O}]Cl2·2H2O (23) were established by X-ray crystallography.
authors.affiliation: Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen Ø, Denmark. anders@kiku.dk.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Temizsoy
authors.forename: Waqas
authors.initials: W
authors.lastname: Sethi
authors.forename: Anders
authors.initials: A
authors.lastname: Reinholdt
authors.forename: Magnus
authors.initials: M
authors.lastname: Schau-Magnussen
authors.forename: Jesper
authors.initials: J
authors.lastname: Bendix
authors.forename: Anders
authors.initials: A
authors.lastname: Hammershøi