苯并噁嗪型MBH加合物的环化反应

Morita–Baylis–Hillman（MBH）加合物是有机合成中一种强力的合成砌块，常扮演一原子或三原子合成子，可以与亲电型偶极体进行环化反应形成多种环状化合物。虽然关于MBH加合物的环化反应的研究已有了诸多报道，但仍主要局限于醛和靛红衍生的两类MBH加合物，导致反应模式单一，反应位点固定，底物范围狭窄等诸多不足。基于此，本论文设计了一类新型的苯并噁嗪型MBH加合物，并开发新的反应模式，增加反应位点，为合成更多具有新颖环状骨架的化合物提供一条高效的合成路径。主要研究工作如下：

开发了手性膦催化的苯并噁嗪型MBH加合物与异氰酸酯的不对称[4+2]环化反应。在温和的反应条件下，以高产率和高对映选择性获得了手性二氢喹唑啉酮衍生物。

发展了手性膦催化的苯并噁嗪型MBH加合物与吡唑啉酮的不对称[3+3]串联环化反应。在温和的反应条件下，以高产率、高对映选择性及非对映选择性合成了四氢吡喃并吡唑化合物，建立了一种绿色、高效合成四氢吡喃并吡唑活性骨架的方法。

发展了无催化剂参与的苯并噁嗪型MBH加合物与α,β-不饱和N-芳基亚胺的[3+2]环化反应，以高收率和高非对映选择性获得了一系列3,4-二氢吡咯衍生物。该反应具有步骤经济性好、原料易得等特点，可用于构建具有结构多样性的二氢吡咯衍生物。

简言之，本文开发了一类新型的MBH加合物，并分别实现了该类底物作为四原子合成子的不对称[4+2]环化反应和作为三原子合成子的不对称[3+3]串联环化反应和[3+2]环化反应。

Morita–Baylis–Hillman (MBH) adducts are powerful building blocks in organic synthesis, often serving as one-atom or three-atom synthons that undergo annulation reactions with electrophilic dipolarophiles to form various cyclic compounds. Although there have been numerous reports on the cyclization reactions of MBH adducts, they have mainly been limited to two classes: those derived from aldehydes and isatin, resulting in rigid reaction patterns, fixed reaction sites, and narrow substrate scopes. Based on this, this paper designs a novel class of benzooxazine-based MBH adducts and develops new reaction modes to increase reaction sites, providing an efficient synthetic pathway for the synthesis of more compounds with novel ring frameworks. The main research works are as follows:

The research group developed a chiral phosphine-catalyzed asymmetric [4+2] cyclization reaction of benzooxazine-based MBH adducts with isocyanates. Under mild reaction conditions, chiral dihydroquinazolinones derivatives were obtained with high yields and high enantioselectivity.

A chiral phosphine-catalyzed asymmetric [3+3] cascade cyclization reaction of benzooxazine-based MBH adducts with pyrazolones was developed. Under mild reaction conditions, tetrahydrofuran-fused pyrazoline compounds were synthesized with high yields, high enantioselectivity, and diastereoselectivity, establishing a green and efficient method for synthesizing tetrahydrofuran-fused pyrazoline scaffolds.

A catalyst-free [3+2] cyclization reaction of benzooxazine-based MBH adducts with α,β-unsaturated N-aryl imines was developed to obtain a series of 3,4-dihydropyrrole derivatives with high yields and high diastereoselectivity. This reaction features good step economy and readily available starting materials, making it suitable for constructing structurally diverse dihydropyrrole derivatives.

In summary, this paper developed a novel class of MBH adducts and realized their asymmetric [4+2] cyclization reactions as four-atom synthons and asymmetric [3+3] cascade cyclization reactions and [3+2] cyclization reactions as three-atom synthons.

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