Exploration On P、N Lewis Base Promoted C-C Bond Forming Reactions Based On Allenoates And MBH Allylic Compounds

Development of highly efficient carbon-carbon bond forming reaction is animportant objective in synthetic organic chemistry. As Lewis bases, phosphines oramines mediated reactions provide highly attractive methods for carbon-carbonbond formation, generally bearing such merits as high efficiency, mild andmetal-free conditions and simple operation. A great deal of effort from chemistrycommunity has been devoted to this area, leading to the discovery of a large numberof new reactions. This dissertation mainly focuses on the exploration of newcarbon-carbon bond forming reactions under the promotion of phosphines or amines.Inspired by the recent findings on phosphine or amine mediated reactions inliteratures, we have successfully developed several new P, N-Lewis base-mediatedcarbon-carbon bond forming reactions, including cyclopropanation, olefination,vinylogous Wittig reaction,[4+2] cycloaddition and [2+2+2] cyclization. Thesereactions are respectively discussed in the following six chapters of this dissertation:In chapter1, the advances in phosphine or amine mediated reactions of therecently intensely studied allenoates and Morita-Baylis-Hillman （MBH） allyliccompounds are briefly reviewed. On the basis of our understanding and analysis onthe findings in literature, we put forth our research objectives.In chapter2, the background of phosphine-mediated reactions of allenoates andaldehydes has been summarized and results on the reactivity of α-substitutedallenoates with aldehydes under the mediation of phosphines has been discussed. Anovel PPh3-mediated reductive cyclopropanation between α-substituted allenoatesand aromatic aldehydes has been developed. It represents the first example of theallene-based synthesis of the smallest carbocycle, as well as an unprecedentedannulation mode of allenoates. Reaction conditions, substrate scope, as well asreaction mechanism have been systematically investigated. It was found that thereaction provides efficient access to highly functionalized cyclopropanes fromsimple and readily available starting materials.In chapter3, the Wittig reaction of in situ formed phosphorus ylide with aldehydes is reviewed, and a phosphine-mediated olefination reaction betweenα-substituted allenoates and aldehydes is unveiled. By choosing more nucleophilicphosphines like PBu₃and PPh2Me, the phosphine-mediated olefination ofα-substituted allenoates with aldehydes is successfully realized. High levels ofchemo-and diastereoselectivity and yield are obtained for a wide scope of substrates,providing an efficient method for stereoselective synthesis of1,2,3,4-tetrasubstituted1,3-dienes from readily available starting materials. The in situ generated allylicphosphorus ylide is believed to be the key intermediate which is responsible for thesubsequent Wittig reaction with the aldehyde. This reaction also evidences thecapacity of phosphines in the control of reaction pathways.In chapter4, the background of vinylogous Wittig reaction is introduced and astereoselective PBu₃-mediated vinylogous Wittig reaction between α-methylallenoates and aldehydes is developed as the first example of a practical andsynthetically useful vinylogous Wittig reaction. Mechanistic experiments includingdeuterium-labeling, intermediate entrapment, and NMR monitoring have beendeliberately conducted. On the basis of mechanistic investigations, a reliablemechanism for the vinylogous Wittig reaction is proposed, which features awater/phosphine-co-assisted allylic phosphorus ylide1,3-rearrangement pathway,rather than previous retro-Diels-Alder ones. Mechanistic findings in this work alsoprovide supportive evidence for typical mechanisms of importantphosphine-mediated reactions of α-substituted allenoates.In chapter5, the reactivity of allenoates and MBH allylic compounds in Lewisbase-promoted annulation reactions has been briefly discussed. Through structuremodification of MBH allylic compounds as well as reaction conditions optimization,a novel DABCO-catalyzed [4+2] annulation of Morita-Baylis-Hillman allylicacetates with electron-deficient alkenes or diazenes has been developed. Thereaction exhibits a broad substrate scope and high efficiency, providing practicalsyntheses of highly functionalized cyclohexenes, tetrahydropyridazines,anthraquinones, and important spirocycles. This reaction represents a new reactivitypattern of the intensely studied MBH allylic compounds acting as a C4synthon inLewis base-catalyzed annulation reactions, and also showcases divergent catalysis between tertiary amines and phosphines.In chapter6, the background of organocatalytic C-H activation is brieflyreviewed and a diastereoselective DABCO-catalyzed [2+2+2] annulation of MBHallylic compounds with arylidenemalononitriles to provide highly functionalizedcyclohexanes is described. The reaction represents the first example of MBH allyliccompounds serving as a C2component for Lewis base-catalyzed annulationreactions. In the annulation, the inert γ-methyl of MBH acetates is involved in thecarbon-carbon bond formation, providing the first example of sp3-C-H activationreaction under Lewis base catalysis.