|关键词||多组分反应 亚胺酸酯 Α-硅基胺 Brook重排 格氏试剂|
Abstract Xiao-Jun Han(Organic Chemistry) Directed by Prof. Chong-Dao Lu It has been a constant pursuit of synthetic chemists to obtain complex molecules from commercial or easily prepared reagents in a one-pot operation without isolation of intermediates. Multicomponent reactions (MCRs) have attracted considerable attention due to the virtue of their convergence, productivity, operationally simple and generally high yields of products. In recent years, the multicomponent reactions involving stabilized carbanions that formed from Brook rearrangement and can be trapped by electrophiles have shown unique advantages in the synthesis of compounds that contain hydroxyl/amino/carboxyl groups, which stimulated the reasearch interests of synthetic community. α-Aryl-α-carbonyl ester/isatin derivatives, as the readily available carbonyl compounds, can be attacked by nuclephilic silyl groups and followed by silyl migration ([1,2]-Brook rearrangement), resulting in carbanions that can be stabilized by the aryl groups and carboxyl groups of the intermediates. Subsueqently, the carbanion can be trapped by electrophiles and completed this [1,2]-Brook rearrangement-mediated tandem reaction. Studies on this aspect have been conducted in this thesis. Imidates, because of their special structure (containing two hetero atoms - nitrogen and oxygen, similar ester and imine structure), may have special reactivities and display some advantages in the construction of some structurally complex molecules. But few studies about imidates were reported. So we studied the multicomponent reactions involving cascade transformation of imidates for the synthesis of α-tertiary α-silylamine. In the dissertation, we mainly focused on the subjects listed as below: 1. An efficient method for the synthesis of α-tertiaryα-silylamines has been developed. The three-component coupling of aryl tosylimidates, silyllithium, and Grignard reagents in a single flask enables the rapid construction of diverse bulky α-silylamine derivatives. The synthetic method is flexible and efficient with yield up to 95% and the reaction was well tolerated. Meanwhile, we have succeeded in synthesis of a series of aryl tosylimidates, which provide effective procedures for their preparation. In the reaction of imidates and silyllithium, three kinds of products including silyl N,O-aminal, acylsilane and acylsilane-derived imine can be obtained respectively by using different reaction quenching conditions. This is also an effective method for the synthesis of these compounds. 2. Three-component reactions of silyllithium, α-carbonyl ester/isatin compound and an electrophilic imine/aldehyde have been studied. The reaction occurred smoothly to furnish densely functionalized β-amino/hydroxy-α-hydroxy esters with a quaternary carbon center in one-pot operation. This reaction can be extended to broad substrates in moderate to high yield (up to 99%), albeit with low to moderate diastereoselectivity (d.r. from 5:1 to 1:1). 3. A high yielding (up to 98%) and excellent diastereoselective (d.r. >20:1 to 8:1) method for the synthesis of α-chiral amines via the addition-reduction reaction of chiral N- N-tert-butylsulfinyl arylimidates and secondary Grignard reagents R2CH-MgX. This synthetic protocol did not suffer from the side reaction that the reaction of secondary Grignard reagents and imines always encountered. In the latter protocol, competing hydride transfer is sometimes dominated reaction pathway over the desired nuclephilic addition of secondary alkyl groups to imines. The disclosure of the described reactivity of N-tert-butylsulfinyl arylimidates has extended their applications in the organic transformations.
|韩晓军. 亚胺酸酯参与/Brook重排介导的多组分反应研究[D]. 北京. 中国科学院大学,2014.|
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