Chiral Lewis Acid-Catalyzed Enantioselective Cycloadditions between Indoles and Cyclic Carbonyl Ylides Derived from Diazodiketone or Diazoketoester Derivatives

Asymmetric 1,3-dipolar
cycloaddition reactions between N-methylindoles and
several cyclic carbonyl ylides that
were derived from diazodiketone or diazoketoester precursors in the
presence of both achiral Rh and chiral lanthanoid metal catalysts
are described. For the six-membered cyclic carbonyl ylides derived
from 1-diazo-5-aryl-2,5-pentanedione precursors, the cycloaddition
reactions were carried out using Rh2(OAc)4 (2
mol %) and the chiral Pybox-Ph2–Lu­(OTf)3 complex (10 mol %) as catalysts, resulting in high enantioselectivities
(83% to >98% ee (exo)) along with relatively good exo-selectivities (exo:endo = 65:35 to 94:6) and yields (63–85%). For the five-membered
cyclic carbonyl ylide derived from 1-diazo-2,4-pentandione precursor,
the cycloaddition reaction with 5-bromo-1-methylindole was carried
out in the presence of Rh2(OAc)4 (2 mol %) and
the chiral Pybox-Ph2–Er­(OTf)3 complex
(30 mol %) as catalysts, resulting in relatively good enantioselectivity
(78% ee) and endo-selectivity (endo:exo = 81:19).

本研究报道了N-甲基吲哚与由重氮二酮（diazodiketone）或重氮酮酯（diazoketoester）前体衍生得到的多种环状羰基叶立德（cyclic carbonyl ylide）之间的不对称1,3-偶极环加成反应（1,3-dipolar cycloaddition），反应体系同时采用非手性铑（achiral Rhodium, Rh）催化剂与手性镧系金属催化剂（chiral lanthanoid metal catalysts）。针对由1-重氮-5-芳基-2,5-戊二酮前体衍生得到的六元环状羰基叶立德，实验以四乙酸二铑（Rh₂(OAc)₄，2 mol%）与手性Pybox-Ph₂-三氟甲磺酸镥络合物（Pybox-Ph₂–Lu(OTf)₃，10 mol%）作为催化体系，最终获得了优异的对映选择性（83% 至 >98% 对映体过量值（enantiomeric excess, ee），外向型（exo）产物），同时具备较佳的外向选择性（exo:endo = 65:35 至 94:6）与反应收率（63%~85%）。针对由1-重氮-2,4-戊二酮前体衍生得到的五元环状羰基叶立德，实验以5-溴-1-甲基吲哚（5-bromo-1-methylindole）为底物，在四乙酸二铑（Rh₂(OAc)₄，2 mol%）与手性Pybox-Ph₂-三氟甲磺酸铒络合物（Pybox-Ph₂–Er(OTf)₃，30 mol%）的催化体系下进行环加成反应，最终获得了较佳的对映选择性（78% ee）与内向选择性（endo:exo = 81:19）。