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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Highly Diastereoselective Hydroxy-Aza-Prins Cyclization: Rapid Access to 4'-Hydroxy Six-Membered Spiro Azacyclic
Hoe Young Choi1, Chan Su Jang1, Jaehwan Kim2
1Department of Chemistry, Kookmin University, 77 Jeongneung-ro, Seongbuk-gu, Seoul 02707, Republic of Korea.
Abstract:
A highly diastereoselective nucleophilic addition of hydroxy-aza-Prins cyclization through umpolung allylation of N-2,2,2-trifluoroethylisatin ketimines is described. This novel synthetic approach controls the stereocenter at the C4' position of 4'-hydroxy six-membered spiro azacyclic oxindoles based on the presence or absence of hydrogen bonding interactions with nucleophiles. The reactions, involving palladium-catalyzed Tsuji-Trost umpolung allylation and aza-Prins cyclization, proceed smoothly with allyl acetate in the presence of Pd(PPh3)4, DBU, H2O, and TMSOTf. This one-pot protocol produces selective axial-4'-hydroxy six-membered spiro azacyclic oxindoles in excellent yields. In contrast, using the acetoxy group as a nucleophile in acetoxy-aza-Prins cyclization enables the synthesis of selective equatorial-4'-acetoxy six-membered spiro azacyclic oxindoles.
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