0 Hits

  • Previous / Next

You are using Science Of Synthesis as a Guest.
Please login to access the full content or check if you have access via Method 1: Chiral Salicylamine Catalyzed Strecker Reaction

DOI: 10.1055/sos-SD-020-00343

Wolkenberg, S. E.; Garbaccio, R. M.Science of Synthesis, (200720415.

The Strecker catalyst 88 (R4=polystyrenemethyl; R5=H; X=S) was discovered and optimized by screening parallel synthetic libraries of resin-bound catalyst candidates for their ability to promote enantioselective addition of cyanide to imines 87 without the use of any metal (Scheme 26).[‌99‌] Validation efforts led to the soluble catalyst 88 (R4=Bn; R5=H; X=O) and further optimization provided a superior catalyst 88 (R4=R5=Me; X=S).[‌100‌] This procedure is very effective for the conversion of both aromatic and aliphatic N-benzyl- or N-allylimines into their corresponding α-aminonitriles 89; however, these products are chromatographically unstable and are best isolated as the trifluoroacetamides or formamides. Mechanistic work on the catalyst structure has demonstrated the important role of the tert-butyl groups in enantioselection, and has revealed that only the urea hydrogen atoms are essential for catalysis by interacting with the imine. Conversion of the α-aminonitriles 89 into the α-amino acids 91 requires four high-yielding steps: formylation of the amine to allow isolation, hydrolysis of the nitrile to give the N-benzyl amino acid 90, deformylation, and debenzylation.

Meeeee 88 Meeeee Meeeeeeeeeee Meeeeeeee Meeeeeee Meeeeeeee[‌888‌]

Meeeeeeeeee 88

M8 M8 eee (%) Meeeee (%) ee 88 Mee
Me MM8MM=MM8 88 88 [‌888‌]
8-Mee MM8MM=MM8 88 88 [‌888‌]
8-Mee MM8MM=MM8 88 88 [‌888‌]
8-Mee MM8MM=MM8 88 88 [‌888‌]
e-Me Me 88 88 [‌888‌]
Me Me 88 88 [‌888‌]
eMe Me 88 88 [‌888‌]
M8M88 Me 88 88 [‌888‌]
eMe Me 88 88 [‌888‌]
eeeeeeeeeee Me 88 88 [‌888‌]

e Mee eeeeeeeeeeeeeee-eeeeeeeee eeeee eeeee (M8 = MM8).

Meeeeeeeeeee Meeeeeeee

α-Meeeeeeeeeeee 88; Meeeeee Meeeeeeee:[‌888‌]

MMMMMMM: Meeeeeee eeeeeee eee ee eeeeeeee eeeeeee eee eeee eee ee eeeeeeeee eeeee.

M eeeee-eeeee, 88-eM, eeeee-eeeeeeee eeeee eeeeeeee eeee e eeeeeee eee eee eeeeeee eeee eee eeeeeeee (8.88 eeeee), eeeeeee (8 eeeee), eee eee eeeee 88 (8 eeeee). Mee eeeeeee eee eeeeeee ee ee eeeee eee eeeeeeee eee eeeeeeeeee eeeeeeeee eee eee eeee eeeeee eeeee 88°M ee eeeee ee e eeeeeeee-eeeeeeeeeee eeee. M eeeee-eeeee eeeeeeee eeeee eee eeeeeeee eeee e eeeeeee eee eee eeeeeee eeee eeeeeee eeeeeeeee eeeeeee eee MMMMM (8.88 eeeee). Mee eeeeeee eee eeeeee ee 8°M; ee eeee eeee, MeMM (8.88 eeeee) eee eeeee eee eeeeeee; eee eeee eee eeeeeee ee eeee ee 8°M eee 8e eee eeee eeeee ee eee eeeee eeeeeeee eeeee ee eeeeeee ee 88°M. Meeee 88e, eee eeeeeeee eee eeeeeeee eee eeee eee eeeeeeeeeeee 88; eeeee: 8888% (8888% ee).

Meeeeeeeeeee ee eee eeeee eeee eee eeeeeeee ee eeeee eeeee: M8MM8 eeeeeeeeee ee eee eeeeeee, MMe eeeeeee ee eee eeeeee eeeee, eee eeeeeeeeeeeee ee eee eeeeee eeeee.