酰基保护的4-氨基-3,4-二氢-1(2H)-萘酮的立体选择性还原反应

The Stereoselective Reduction of Acyl Protected 4-Amino-3,4-dihydro-1(2H)-naphthalenone

1,2,3,4-四氢-1-萘胺及其衍生物是一类重要的药物合成中间体.从光学纯的(R)-和(S)-1,2,3,4-四氢-1-萘胺出发,首先经乙酰化、苯甲酰化和邻苯二甲酰化反应制备相应酰胺,然后在高锰酸钾作用下氧化生成了氨基萘酮衍生物,收率为65%～85%.这些不同酰基保护的氨基萘酮衍生物经硼氢化钠(NaBH4)和二异丁基氢化铝(DIBAL-H)还原后得到两种构型的氨基萘醇混合产物,经二维核磁共振氢谱的核磁欧沃豪斯效应(NOE)推断,此还原反应的主产物是顺式构型的氨基萘醇,当(R)-或(S)-邻苯二甲酰化的氨基萘酮经DIBAL-H还原后主产物为顺式的氨基萘醇4ca和7ba,其非对映异构体过量(de)百分比分别为92.6%和98.2%.

1,2,3,4-Tetrahydronaphthalen-l-amine and its derivative were a series of important synthetic intermediates for bioactive compounds. Acylation of optically pure （R） - and （S） - 1, 2, 3, 4 - tetrahydronaphthalen-l-amine with acetic anhydride, benzoyl chloride and phthalic anhydride followed by oxidation with potassium permanganate to give acylated aminonaphthyl ketones in yields of 65% 85%. These aminonaphthyl ketones were reduced stereoselectively by sodium borohydride（NaBH4） or diisobutylaluminium hydride（DIBAL-H） to afford the aminonaphthyl alcohols mainly in cis-form, which was confirmed by nuclear Overhauser effect（NOE） obtained by 2D 1H NMR. When （R）-and （S）- phthalic protected aminonaphthyl ketone was reduced with DIBAL-H, cis-aminonaphthyl alcohols 4ca and 7ba were obtained as major product in diastereomeric excesses＇（de） percentages of 92.6% and 98.2%, respectively.