第二章 Retrosynthetic Analysis (逆合.pptVIP

第二章 Retrosynthetic Analysis (逆合成分析法) Acyl anions derived from cyanohydrins may be generated catalytically by cyanide ion via the Stetter reaction. Acyl anions derived from enol ethers Acyl anions derived from lithium acetylide 1.3 Steps in planning a synthesis Key interrelated factors: ★ Construction of the carbon skeleton ★ Functional group interconversions ★ Control of relative stereochemistry ★ Control of enantioselectivity Construction of the carbon skeleton Formation of new C-C bonds are of paramount importance in organic chemistry. Important C-C-bond-forming reactions Important C-C-bond-forming reactions Some important guidelines for choosing disconnections of bonds. ★ Disconnection of bonds should be carried out only if the resultant fragments can be reconnected by known and reliable reactions. ★ Aim for the fewest number of disconnections ★ Choose disconnetions in which functional groups are close to the C-C bonds to be formed. ★ It is often advantageous to disconnect at a branching point, leading linear fragments. ★ A preferred disconnection of cyclic esters (lactones) or amides (lactams) produce hydroxy-carboxylic acids or amino-carboxylic acids as targets ★ Functional groups in the TM may be obtained by functional group interconversion ★ Symmetry in the TM simplifies the overall synthesis. ★ Introduction of an activating (auxiliary) functional group may facilitate C-C bond formation. ★ There is no simple way to disconnect the TM shown below. However, the presence of a 1,6-dioxygenated compounds suggests opening of a six-membered ring. ★ Disconnection of an internal (E)- or (Z)-double bond or a side chain of an alkene suggest a Wittig-type reaction or an alkylation of a vinylcuprate, respectively. * Basic concepts Retrosynthetic analysis: The construction of a synthetic tree by working backward from the target molecule. Disconnection: cleavage of a C-C bond Functional group interconversions A synthetic tree Chemcal bonds can be