1 2 3 4 disconection synthetic precursor disconection

第二章作业题 1. 2. 3. 4. 简单表示逆合成分析法的基本思路 掌握逆合成分析法下列概念的中英文名称及含 义即：disconection, synthetic precursor, , disconection approach, synthetic equivalent, retron, transform, TGT, TM, SM, EXTGT tree, refunctionalization, FGI, FGR, FGA, FGT. 了解切断碎片的分类 了解Corey逆合成分析法的五大策略

Synthesis must always be carried out by plan, and the synthetic frontiers can be defined only in term of the degree to which the realistic planning is possible utilizing all of the intellectual and physical tools available. ---R. B. Woodward, 1956

Mannich Reaction

Robinson utilized a tandem sequence in a simple one-pot procedure which involves two consecutive Mannich reactions: the first one in an interand the second one in an intramolecular fashion. In a way, the total synthesis of tropinone by Robinson was quite ahead of its time both in terms of elegance and logic. With this synthesis Robinson introduced aesthetics into total synthesis, and art became part of the endeavor.

2. 2 Corey的逆合成分析法 （Restrosynthetic Analysis ） 反合成分析理论（Antithetic Analysis） J. Am. Chem. Soc. 1964, 84, 478. General Methods for The Construction of Complex Molecules Pure & Applied Chemistry. 1967, 14(1), 19. The Logic of Chemical Synthesis, John Wiley & Sons, Inc. 1989.

2. 2. 1 逆合成分析法基本思路 逆合成分析的过程 Restrosynthetic Analysis. A problem-solving technique for transforming the structure of a synthetic target molecule to a sequence of progressively simpler structure along a pathway which utimately leads to simple or commercially available starting materials for a chemical synthesis.

The Bond Polarization Model The sites marked d represent donor sites or nuclephilic atoms The sites marked a are acceptor sites and electrophilic atoms Bond polarization induced by the heteroatom extends down the carbon chain due to the usual inductive effects that are a combination of through-space and through-bond effects. The electrophilic carbon (C 1) adjacent to X is designated an acceptor atom since proximity to the electronegative atom (X) induces the opposite polarity. Similarly, C 2 is a donor atoms, but weaker than X, and C 3 is a weak acceptor atom. As a practical matter, the effect is negligible beyond C 4 and will ignored.

Disconnection Approach 切断法 Fragment Equivalent Ph. CH 2+ Ph. CH 2 Br Ph. CH 2 - Ph. CH 2 Mg. Br CH 3 CH 2+ CH 3 CH 2 Br CH 3 CH 2 - CH 3 CH 2 Mg. Br Ph. CH 2 CH+-OH Ph. CH 2 CHO CH 3 CH 2 CH+-OH CH 3 CH 2 CHO ? ?

Fragments Ionic Fragments Equivalents It is often difficult to handle and prepare α-chloroketone Enolate alkylation is perfered

The follow route can be obtained by the retrosynthesis based on disconnection 2. 作业：列出此路线逆合成中的切断碎片和对应的等效剂 The route 1 is considered better than the route 2 since it involves simple reagents and is shorter.

2. 2. 4 转换(Transform) 和反向子(Retron) Transform. The exact reverse of a synthetic reaction such that when applied to the structure of a reaction product it results in the generation of reactant structure(s). 切断产生碎片并找到等效剂（合成前体）的过程。 Retron. The minimal substructural element in a target structure which keys the direct application of a transform to generate a synthetic precursor. 反向子，反合成元，即发生转换所涉及到的最小的结 构单元。

Retron of Diels-Alder Tf 由此可见，D-A转换会有很多 种，这样的Retron就会有许多回 推结果，像这样的Retron，Corey 称之为Supra Retron。 A stuctural subunit in target molecule which consists not only of a complete retron for a particular transform but also of additional structural elements which signal the applicability and effectiveness of that transform. A supra retron contains ancillary keying group in addition to those of the basic or minimal retron.

分子骨架C-C键和官能团均变化的转换 TGT Retron Transform Pinacol Rearrangement Tf Beckmann Rearrangement Tf Claisen Rearrangement Tf Precursor(S)

J. Chem. Inf. Model. , Vol. 49, No. 3, 2009, 593 -602