光学纯1,1'-(4,6-二苯并呋喃二基)双乙基-1-醇/胺的合成探索

Synthetic Exploration of Optically Pure 1,1'-(Dibenzo[b,d]furan-4,6- diyl)bis(ethan-1-ol/amine)

摘要:

以二苯并呋喃（Ⅱ）为起始原料，与仲丁基锂（s-BuLi）、四甲基乙二胺（TMEDA）、乙醛（CH3CHO）反应，得到1,1'-(4,6-二苯并呋喃二基)双乙基-1-醇（Ⅲa），然后在氯铬酸吡啶嗡盐（PCC）中经过氧化反应得到1,1'-(4,6-二苯并呋喃二基)双乙基-1-酮（Ⅳa），随后在(S)-2-甲基-CBS-噁唑硼烷{(S)-MeCBS}催化下采用硼烷-二甲硫醚（BH3-Me2S）还原，重结晶后得到 (1R,1'R)-1,1'-(4,6-二苯并呋喃二基)双乙基-1-醇（Ⅰ）。最佳反应条件为n(Ⅱ): n(s-BuLi): n(TMEDA): n(CH3CHO)= 1：3：3.3：2.2，n(Ⅲa): n(PCC)=1: 4，n(Ⅳa): n [(S)-MeCBS]: n(BH3-Me2S)=1: 0.6: 3, 三步反应总收率为32%。在化合物I中，存在一定的分子内氢键，影响了羟基进一步衍生。采用Ⅲa经过氯化亚砜氯代，叠氮化钠取代和钯碳氢化还原，得到消旋1,1'-(4,6-二苯并呋喃二基)双乙基-1-胺（Ⅶ），加入常见手性酸利用成盐拆分的方法未能得到光学纯1,1'-(4,6-二苯并呋喃二基)双乙基-1-胺（Ⅷ）。

Abstract:

Reaction of dibenzofuran(Ⅱ) with sec-butyl lithium (s-BuLi)/tetramethyl ethylene diamine (TMEDA) /acetaldehyde(CH3CHO) gave 1,1'-(dibenzo[b,d]furan-4,6-diyl)bis(ethan-1-ol)(Ⅲa) which was then oxidized by pyridinium chlorochromate (PCC) to yield 1,1'-(dibenzo[b,d]furan-4,6-diyl)bis(ethan-1-one)(Ⅳa). Subsequent reduction of IV-A by borane-dimethyl sulfide (BH3-Me2S) in the presence of a catalytic amount of  (S)-2-methyl-CBS-oxazo borane{(S)-MeCBS} followed by recrystallization gave optically pure (1R,1'R)-1,1'- (dibenzo[b,d]furan-4,6-diyl)bis(ethan-1-ol) (Ⅰ). The optimal reaction conditions are as follows: the molar ratio of Ⅱ: s-BuLi: TMEDA: CH3CHO is 1: 3: 3.3: 2.2, the molar ratio of Ⅲa: PCC is 1: 4, the molar ratio of Ⅳa: (S)-MeCBS: BH3-Me2S is 1: 0.6: 3, and the overall yield of the three-step reaction is 32%. An intramolecular hydrogen bond of compound (Ⅰ) affects further diversifications of its hydroxyl group to some extent. The racemic 1,1'-(dibenzo[b,d]furan-4,6-diyl)bis(ethan-1-amine) (Ⅶ) was obtained starting from Ⅲa via a successive process of chlorination with thionyl chloride, azidination with sodium azide and Pd/C-catalyzed hydrogenation. However, the resolution of Ⅶ by commonly used chiral carboxylic acids to obtain optically pure 1,1'-(dibenzo[b,d]furan-4,6 -diyl)bis(ethan-1-amine)(Ⅷ) was not successful.