乙烯基取代苯並惡嗪酮、環氧乙烷與氮丙啶經由過渡金屬烯丙基兩性離子之催化環加成

Abstract

雜環廣泛存在於自然中，其自身與在有機化學的價值吸引了相當大之關注。就這些迷人結構之合成而言，偶極環化加成提供了有效的策略，並且得以控制其化學、區域與立體選擇性。於眾多合成單元之中，兩性離子結合了以碳、氮或氧中心為親核試劑，與親電烯丙基金屬基團，以展現出多樣的反應性。其中乙烯基衍生物為最實用的前驅物。本論文闡述含螺環在內的催化環加成之進展。 首先，我們合成乙烯基苯並惡嗪酮，此為環狀烯丙基氨基甲酸酯，與亞芳基異噁唑酮及二氫吡唑啉酮作為環外活性烯烴，且經由鈀催化脫羧環加成得到螺狀四氫喹啉。其過渡態包含關鍵的六元環氫鍵模型。此外，結合與協作者的研究，環狀與非環狀烯丙基氨基甲酸酯建構了選擇性之分子內及分子間碳、氮烯丙基化步驟。 其次，合成兩種由六元或五元環外烯烴構成之乙烯基環氧乙烷，且於鈀催化下展現發散的反應性。其中具有色烷或四氫化萘骨架之起始物經由環化加成得到螺狀氨基甲酸酯與螺狀氨基甲酰亞胺酯，且具有螺位組態之保留或反轉的現象。此外，建構於茚滿骨架的化合物可有效地轉化為包含高反應性亞乙烯基官能團之苯並富烯。且經由連續的氧化、腙環化加成與自發脫氫合成噠嗪衍生物。 最終，合成具有缺電子烯烴的乙烯基氮丙啶，且於銠催化下與炔類進行環化加成。依據水氣的存在與否，可選擇性地生成氨基酮及吡咯啉產物。對於吡咯啉而言，藉由有機鹼誘導烯烴遷移與最終之三氟乙酸促進芳香化可轉化為吡咯，並進而優化為簡便的一鍋化操作。

Heterocycles are ubiquitous in nature which attract considerable attention as itself and the valuable scaffolds in organic chemistry. In terms of its synthesis, dipolar cycloadditions provide efficient protocols to these fascinating architectures with control of chemo-, regio- and stereo-selectivity. Amongst numerous 1,n-synthons, vinyl motifs are the most practical precursors of zwitterions which combine both electrophilic π-allyl metal fragments and C-, N- or O-centered nucleophiles to exhibit versatile reactivities. In this thesis, achievements in catalytic annulations inclusive of spirocyclic frameworks are addressed. First, vinyl benzoxazinanones, the cyclic allyl carbamates, and the exocyclic active olefins arylidene- isoxazolones or dihydropyrazolones were synthesized and subjected to accomplish spirocyclic tetrahydroquinolines via a palladium-catalyzed decarboxylative cycloaddition. An unprecedented divergence on configurations is controllable from the substrates with or without protecting group. Representative models inclusive of a vital six-membered hydrogen bonding interaction were suggested. Accumulated with collaborator’s study, a fascinating regiodivergent decarboxylative assembly was established. A selective C-/N-allylation process via intra-/inter-molecular manner was demonstrated by starting substrates on a cyclic or acyclic backbone. Second, two kinds of vinyl oxiranes consisting an exocyclic olefin on six or five membered skeletons were synthesized and performed divergently under palladium catalysis. Substrates on chromane or tetralin successfully achieve spiro carbamates and carbamimidates via a [3+2] cycloaddition, and racemization on spiro center was discovered. Descriptive models on rapidity of heterocumulenes interception and outer-sphere annulation were recommended for interpreting the retentive versus inversive cyclization. Parallelly, compounds on an indane skeleton were effectively transformed into the 2-carbinol substituted benzofulvenes containing a highly reactive vinylidene functionality. Pyridazine derivatives could be synthesized through the consecutive oxidation, hydrazine-mediated dehydrative cycloaddition and spontaneous dehydrogenation. The last, vinyl aziridines with an electron deficient C=C were synthesized and subjected to rhodium catalysis with acetylenes. Two series of products, γ-amidoketones or pyrrolines were selectively constructed according to the presence or absence of moisture. For [3+2] cycloadduct pyrrolines, acidity of bisallylic methine is enhanced by introduction of a terminal ester or ketone functionality. The subsequent DABCO promoted C=C migration and the ultimate TFA assisted aromatization were disclosed and further modified to one-pot manipulations for delivering the substituted pyrroles.