钛酸四异丙酯促进的双格式试剂串联反应方法学研究

Organotitanium catalysts were widely used as its high effective, environmental friendly, and cheaper than other transition metal catalysts. A novel carbon-carbon bond forming method will be developed for the one-pot reaction of Ti(O-i-Pr)4 mediated arylation of dual Grignard reagents to aldehyde, ketone or epoxide. This methodology will use different allylbromide to gain either allyl benzene structures or tertiary alcohols containing terminal alkenes. The former were usually acted as intermediates for the synthesis of natural or synthetic drugs. The latter was a break-through in the organic synthesis, because tertiary alcohols were usually gained from ketones with Grignard reagents. Few literature reported approaching tertiary alcohols starting with aldehyde. We are going to investigate its reaction mechanism. This project will fill up the gaps in the organotitanium chemistry as well as provide new approaches to the arylated homoallyl alcohols.

有机钛催化剂以其性价比高、环境友好以及不易引起副反应而得到了广泛的应用。此项目将要发展一种通过钛酸四异丙酯促进的双有机格式试剂对醛、酮及环氧化合物进行的串联偶联反应来构建碳碳键的方法。该方法能利用不同碳链长度的烯基溴试剂分别合成低活性的高烯丙醇末端双键偶联产物或者含有末端双键的叔醇类化合物。前者通常是天然产物或者药物的重要中间体；后者由醛为起始原料合成末端双键的叔醇类化合物是一个有机合成的突破，因为叔醇类化合物通常都是由格式试剂对酮加成获得，几乎没有文献报道由醛类化合物为原料获得，我们将要对其催化机理进行推测和实验验证。此项目为有机钛试剂的发展开拓了新的路径。

有机钛试剂由于其独特的特性，包括性价比高、无毒副作用、环境友好以及不易引起副反应等特点得到了广泛的应用。该项目发展了两种通过钛酸四异丙酯介导的双有机格氏试剂对醛酮以及环氧类化合物进行的串联偶联反应来构建碳碳键的新方法。第一种方法以醛酮或环氧化合物为原料，经烯丙基溴格氏试剂或烯基溴格氏试剂，随后串联钛酸四异丙酯介导的溴苯格氏试剂对高烯丙醇末端双键的加成，该方法适用性比较广，收率较好。第二种方法以醛为原料，经长链烯基溴格氏试剂加成，随后串联钛酸四异丙酯介导的溴苯格氏试剂直接对和氧原子相连的碳原子进攻得到高烯丙基叔醇类化合物，该方法开拓出由醛类化合物合成非对称性叔醇类化合物的先河，对该类化合物的合成提供新的方法。