Studies On Novel Annulation Modes Of Two All-carbon Synthons:Cyclobutenones And Propargyl Esters

The subject elaborated in this thesis mainly focuses on the development of novel cycloaddition and cyclization modes base on some simple and readily available all carbon building blocks.The first type was cyclobutenones. As a type of C4 synthon building block, cyclobutenones reacted with gem-cyano alkenes in a [4+2] cycloaddition manner under the catalysis of nucleophilic Ph2PMe to produce multisubstituted cyclohexenones. Generally speaking, the organo-phosphine catalyzed cycloadditions were initiated by the conjugate addition of the strong nucleophilic but weak basic P atom to the C-C multiple bonds, such as alkenes, allenes and alkynes, but herein we introduced was another unclassical activation mode, that is the nucleophilic P atom chemoselectively attacking the the carbonyl group of cyclobutenones. The subsequently formed oxygen anion triggered C-C single bond cleavage and therefore furnished a novel type of vinyl-enolate-based 1,4-dipoles. [4+2] Cycloaddition of this unprecedental 1,4-dipole with isatylidenemalononitrile afforded the spirocyclohexenone oxindole product, the skeleton of which was very similar to that of some small bioactive small molecules, such as MDM2-p53 inhibitor B. Under the catalysis of phenylanine-derived LB-BA bifunctional chiral phosphine catalyst, the asymmetric 1,4-dipolar spiroannulations produced the enantio-enriched 3-spirocyclohexenone-2-oxindoles in good to excellent yields with up to 87% ee.In order to convert the above [4+2] cycloaddition reactions into highly enantioselective versions, a novel types of LB-BA bifunctional chiral phosphine catalyst, called Xiao-Phos, with a distinctive single hydrogen bonding donor-N-H of the chiral tert-butyl sulfinamide, were designed and synthesized. Xiao-Phos was readily prepared from a two-step synthetic procedure:condensation of the commertially available aldehyde with (R)-tert-butylsulfinamide afforded the (Rs)-sulfinimine, and then diastereoselectively 1,2-addition of the Ph2PCH2Li to the chiral (Rs)-sulfinimine resulted in the formation of (R,Rs)-Xiao-Phos as the main diastereoisomer. The performance of Xiao-Phos was unsatisfactory in our newly developed [4+2] cycloaddition reactions of cyclobutenones, however, it induce perfect enantioselectivities in some other already kwon reactions, such as Rauhut-Currier reactions, which had been proved by the research works of other members in our group.The second type was propargyl esters. Under the catalysis of PicAuCl2, Rautenstrauch rearrangement of propargyl ester afforded the vinyl-carbene as the key intermediate, which was subsequently captured by the nucleophilic 2-vinylindoles. Thus, intermolecular [4+3] annulation occurred, involving in two molecules of propargyl ester, to furnish the indole-fused cycloheptadiene derivatives, tetrahydrocyclohepta[b]indoles, in absolute trans-diastereoselectivity. It is noteworthy that it was the first time for 2-vinylindole to participate in [4+3] annulation reactions, which used to be employed as diene in the [4+2] cycloadditions. Besides, by simply adding NaOH and MeOH to the reaction solution after the [4+3] annulation finished, a novel kind of "one pot" cascade reaction was developed, which included three types of reactions in all--Au(?)-catalyzed [4+3] annulation, hydrolysis of esters and transannular Adol reaction. Highly functionalized indole-fused bicyclo[3.2.1]octane derivativs were synthesized as a single regioisomer and diastereoisomer by this simples, "one pot" cascade operation.