Oxygen → 3-(2-Nitrophenyl)propanal

HRID 1752842ノート

反応式

HRID 1752842 の反応式
[N:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)=[O:2].[O:9]=O.N1CC[CH2:16][C@H:12]1[C:13](O)=[O:14]>CC#N>[N+:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:16][CH2:12][CH:13]=[O:14])([O-:9])=[O:2]

参加物

5

反応物 3

HCID 977OxygenHCID 11473NitrosobenzeneHCID 145742L-Proline

生成物 1

HCID 105592503-(2-Nitrophenyl)propanal

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

According to Table 1, the α-aminooxylation reaction of 4,5 substituted o-nitro hydrocinnamaldehyde 4a with nitrosobenzene as oxygen source was carried out in the presence of L-proline (20 mol %) in CH3CN at −20° C. for 24 h to obtain α-aminooxylate o-nitrohydrocinnamaldehyde. Since α-aminooxy aldehydes are prone to racemization, it was immediately in situ subjected to catalytic hydrogenation [10% Pd/C, (1 atm) H2] by distilling out CH3CN under reduced pressure and adding MeOH into it, which gave 3-hydroxy THQ 5a in 62% yield with moderate enantioselectivity (82% ee). The low ee could possibly be due to the racemization occurring during the removal of CH3CN at slightly elevated temperature (45° C.). To obtain high enantioselectivity, a mixed solvent system of CH3CN/MeOH (1:3) was used, 5a was obtained in higher enantioselectivity (96% ee) with low yield (52%). In order to improve the yield of THQs, the inventors were further conducted experiments in several solvent systems (CHCl3, CH2Cl2 and THF). However, there was no significant improvement in yields observed in each case. Subsequently, the best result (71% yield, 96% ee) for 5a was obtained when α-aminooxylation was carried out in DMSO and the intramolecular reductive cyclization done, in MeOH in a sequential manner at ambient temperature (entry 7; Table 1).

出典と根拠

ORDレコード
ord-f36dc6b453eb433a84ac0176cc0d9119
出典データセット
uspto-grants-2015_10
特許番号
US09163038B2

反応ノート

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