不對稱催化製備螺氧雜吲哚環戊二烯[c] chromen-4-ones和藉由分子內Wittig反應合成多種類雜芳烴

Abstract

PART-I This part contains one chapter, which illustrates the importance of organocatalytic stepwise (3+2) cycloaddition reactions. Also describe about all carbon 1,3-dipoles and its reactions, specifically formation of all carbon spiro-rings via cycloaddition reactions. CHAPTER-1: “Enantioselective Construction of Spirooxindole-Fused Cyclopenta[c]chromen-4-ones Bearing Five Contiguous Stereocenters via a Stepwise (3+2) Cycloaddition.” In this section, we demonstrated bifunctional quinine-catalyzed stepwise (3+2) cycloaddition for the enantioselective construction of spirooxindole-fused cyclopenta[c]chromen-4-one derivatives. The reactions of 3-homoacylcoumarins and alkylidene oxindole electrophiles generate aforementioned spirooxindole-chromenone adducts bearing five contiguous stereocenters, of which one is the spiro all-carbon quaternary stereocenter in high yields (up to 99%) with excellent stereoselectivities (up to >20:1 dr and 99% ee). Different Michael acceptors such as alkylidene oxindole esters, ketones and benzylidene oxindoles were investigated for the substrate scope of this stepwise (3+2) cycloaddition reaction. This methodology was investigated for three different alkylidene oxindole electrophiles and could also be practically demonstrated on a gram scale. Mechanistic investigations revealed that the (3+2) cycloaddition for the enantioselective synthesis of spirooxindole-fused cyclopenta[c]chromen-4-ones is proceeding via a stepwise reaction pathway. Key words: Stepwise (3+2) cycloaddition reaction, spirooxindole, cyclopentachromenones. PART-II This part is subdivided into three chapters, which illustrates the brief history of Wittig reaction, its development throughout these years and its applications toward synthesis of diverse heteroarenes. In addition, the brief introduction about some elegant synthetic methods of 6/5/5 and 6/6/5 framework of heteroarenes and its biological importance is discussed. Moreover, discussion about formation C–C bonds using different protocols such as the MBH reaction , RC type reaction and its importance in organic chemistry. CHAPTER-2: “Construction of Indeno[1,2-b]pyrrole derivatives via Chemoselective Phosphours Zwitterion Formation/N-Acylation/Wittig Reaction.” This section demonstrates an efficient method for the construction of the indeno-[1,2-b]pyrroles is reported from the phosphorus zwitterions and acyl chlorides in the presence of Et3N via an unprecedented chemoselective N-acylation/cyclization/intramolecular Wittig reaction sequence. A series of new type of phosphorus zwitterions are readily prepared from the indane-1,3-dione hydrazone derivatives, aldehydes, and phosphines through a chemoselective tandem three-component reaction. The mechanistic investigations revealed that the formation of spiro-indene-1,2'-[1,3,4]oxadiazol is the key step for the synthesis of aforementioned heteroarenes. Further, these spiro-indene-1,2'-[1,3,4]oxadiazol compounds were prepared in a reaction of phosphorus zwitterion embedded with PPh2Me, acyl chloride and base, thereby realizing a diversity-oriented synthesis. In addition, our protocol allowed to synthesize the rearranged indeno-[1,2-b]pyrroles via an intramolecular acyl group transfer and Wittig reaction. Key words: chemoselectivity; indeno[1,2-b]pyrroles; N‒acylation; phosphorus zwitterions; Wittig reactions. Chapter 3: “Phosphine-Mediated MBH-Type/Acyl Transfer/Wittig Sequence for Construction of Functionalized Furo[3,2-c]coumarins.” Our group has long been devoted toward the in situ generation of phosphorus zwitterions or phosphonium salts by the addition of phosphine to conjugated carbonyl compounds at different positions for their subsequent Wittig reaction. In continuation of the legacy of our research, we were interested in the development of new methods for the synthesis of privileged heterocycle scaffolds. Thus, herein we developed a new method for the construction of functionalized furo[3,2-c]coumarins via MBH-type/acyl transfer/Wittig reaction. This methodology features O-acylation of zwitterions which were formed by the MBH-type reaction of PPh3 to alkynoates, generating the betaine intermediates that further resulted in the aforementioned heteroarenes via an unprecedented acyl transfer/Wittig reaction. The simultaneous formation of two heterocycles with installing a keto functionality on the aryl ring of the furo[3,2-c]coumarin has been realized from the terminal alkynoates and acyl chlorides in a metal-free one-pot reaction. Furthermore, this protocol could also be applicable to the internal alkynoates/propiolamides to generate the 2,3-disubstituted furo[3,2-c]coumarins and furo[3,2-c]quinolinones via MBH-type/Wittig reaction. To investigate the mechanism, we have performed several control experiments and we prove that acyl transfer between O-to C-acylation by using acyl chloride addition sequence and was confirmed by X-ray analysis. Key words: MBH reaction, Furo[3,2-c]coumarin, acyl transfer, Wittig strategy. Chapter 4: “An efficient method for the Construction of spiro[cyclopenta[c]chromene-indoline]dione derivatives via RC-type/acyl transfer/Wittig strategy.” This section discusses an efficient method for the synthesis of spiro[cyclopenta[c]chromene-indoline]dione derivatives via RC-type/acyl transfer/Wittig strategy. The spiro product was obtained under mild and metal-free conditions from simply oxindole bearing alkyonate as starting material with good to high yields. The simultaneous formation of two heterocycles via RC type/Wittig reaction aforementioned spiro[cyclopenta[c]chromene-indoline]diones from the terminal alkynoates, PPh3 and acyl chlorides. Further investigations to access multifarious heteroarenes utilizing this protocol are underway in our laboratory. Key words: RC-type reaction, Spiro[cyclopenta[c]chromene-indoline]dione, terminal alkynoate.