Stereoselective Bond Formation Research Articles

Unnatural Lysines with Reduced Sidechain N‐Basicity: Synthesis of N‐trifluoroethyl Substituted Lysine and Homologs

AbstractThe syntheses are reported of Nϵ‐(2,2,2‐trifluoroethyl)‐D, L‐lysine (tFK) and Nζ‐(2,2,2‐trifluoroethyl)‐D, L‐homolysine (tFK+1) from amino alcohols HO−(CH2)n−NH2. The syntheses involve reductive amination, Appel bromination, and the stereoselective bond formation between Cα of the amino acid and the fluorinated alkyl chain in the Schöllkopf bislactim amino acid synthesis. The methyl esters of the fluorinated amino acids are the relevant substrates for oligopeptide synthesis. With the R‐Schöllkopf reagent, we stereoselectively generated methyl Nϵ‐boc‐Nϵ‐(2,2,2‐trifluoroethyl)‐L‐lysinate and methyl Nζ‐boc‐Nζ‐(2,2,2‐trifluoroethyl)‐L‐homolysinate. Products and intermediates were characterized by 1H NMR, 13C NMR, COSY, HSQC, and LCMS. A variety of N‐functionality may be introduced by reacting hemiacetals with different appendages. This fluorine modification reduces the sidechain N‐basicity by combined ‐I effect of the three fluorines. This effect increases the [amine]/[ammonium ion] ratio of the sidechain amine in lysine to facilitate carbamylation at lower pH conditions.

Green organophotocatalysis. TiO2-induced enantioselective α-oxyamination of aldehydes

Asymmetric C–O bond formation with various aldehydes is examined under conditions of environmentally benign photo-organocatalysis. A heterogeneous TiO2 photocatalyst is used as a photooxidant in place of toxic and expensive chemical oxidants, for the first time in chemo- and stereoselective bond formation.

Asymmetric Electrophilic α‐Amidoalkylation, VII1): Generation, Crystal Structure, and Trapping Reactions of a Chiral 6,7‐Dimethoxy‐1,2,3,4‐tetrahydroisoquinoline Derived N‐Acyliminium Ion

AbstractThe camphanic acid amide 4 has efficiently been oxidized with triphenylcarbenium tetrafluoroborate (3) to yield the chiral N‐acyliminium ion 1. Trapping reactions of 1 with the silyl nucleophiles 7a‐c and 10a‐f proceeded with stereoselective bond formation, affording the diastereomers (R)‐8/(S)‐9a‐c and (R)‐11/(S)‐12a‐f, respectively, with diastereoselectivities of up to 93.9/6.1.The amido ketones (R)‐8/(S)‐9a‐c were employed in the synthesis of the secondary amines (R)‐16a‐c, (S)‐16a and for the preparation of (−)‐homolaudanosine (R)‐18.By X‐ray crystallography the conformation of 1 in the crystal lattice was established and the preferred conformation of 1 in solution was elucidated by NOE experiments. Finally, the addition reaction of 7a to the iminium ion 21 derived from menthyl carbamate 20 was investigated, which reaction, however, proceeded only with insignificant asymmetric induction.