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Enantioselective Synthesis of Chiral α‑Azido and α‑Aryloxy Quaternary Stereogenic Centers via the Phase-Transfer-Catalyzed α‑Alkylation of α-Bromomalonates, Followed by SN2 Substitution

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journal contribution
posted on 17.04.2017, 00:00 by Doyoung Kim, Min Woo Ha, Suckchang Hong, Cheonhyoung Park, Byungsoo Kim, Jewon Yang, Hyeung-geun Park
A new efficient synthetic method for chiral α-azido-α-alkylmalonates and α-aryloxy-α-alkylmalonates was developed. The enantioselective α-alkylation of diphenylmethyl tert-butyl α-bromomalonate under phase-transfer catalytic conditions [(S,S)-3,4,5-trifluorophenyl-NAS bromide, 50% KOH, toluene, and −40 °C) provided the corresponding α-bromo-α-alkylmalonates in high chemical yields (≤98%) and high optical yields (≤99% ee). The resulting α-alkylated products were converted to α-azido-α-alkylmalonates (≤96%, ≤97% ee) and α-aryloxy-α-alkylmalonates (≤79%, ≤93% ee) by SN2 substitution with sodium azide and aryloxides, respectively.