Studies On The Asymmetric Synthesis Of Allenes With A Central Chirality And The Palladium-catalyzed Cascade Reactions Of Allenes

Allenes are a class of compounds containing a unique1,2-propadiene structural unit with high reactivity. Great efforts have been made on the allene chemistry in the past few decades. In addition, allenes widely exist in natural products and pharmaceutical molecules. The reactions of allenes have been applied as the key steps in the synthesis of some natural products, pharmaceuticals, and materials. Based on the previous observations in our group, my attention has been focused on the asymmetric synthesis of chiral allenes bearing with a central chirality or a center and an axial chirality and the palladium-catalyzed cascade reactions of such allenes.This dissertation includes two parts:Part1:The asymmetric synthesis of allenes bearing with a central chirality1. The asymmetric synthesis of2,3-allenyl malonatesWith2,3-allenol acetates as the starting materials, diethyl malonate as the pronucleophile, and K2CO3as the base, chiral2,3-allenyl malonates could be obtained in71-84%yield and92-96%ee under the catalysis of [Pd(π-cinnamyl)Cl]2/(R or S)-DTBM-segphos. One equivalent of water has been proved to be crucial to ensure a high-yielding reaction. The SEM study shows that the size of K2CO3with1equiv of water is much smaller than that without water.Allenes with both axial and central chirality could be obtained with3.2/1dr value under the optimized conditions when R group was introduced to the terminal position of the allene chain. But the diastereoisomers could not be separated by chromatography even though one of the enantiomer has a high ee value (98%ee).2. The asymmetric synthesis of2,3-allenyl aminesWith2,3-allenol phosphates as the starting materials, TsNHR as the nucleophiles, and DBU as the base, chiral2,3-allenyl amines could be obtained in47-90%yields and88-94%ee under the catalysis of [Pd(π-allyl)Cl]2/(R or S)-3,4,5-(MeO)3-MeOBIPHEP. The R group could also be2,3-allenyl, allyl, and alkynyl, which makes the products to be important starting materials in organic synthesis. Part2:Palladium-catalyed cascade reactions of allenesA Pd(OAc)2-catalyzed reaction of2,3-allenyl malonates or2,3-allenols with o-iodobenzaldehyde or its N-tosyl imine occurred smoothly in MeCN at80℃to form the oxa-or aza-bridged benzo[a,d]cycloheptane derivatives with important biological potentials. With the optically active2,3-allenols and the absolute configurations of all the three chiral centers could be conveniently established.