Research On Palladium-catalyzed Cross-coupling Reactions On Basis Of Alkynes

The transition-metal-catalyzed cross-coupling reaction continues to be a very importantfield of organic synthesis chemistry. Among the transition metals, palladium plays animportant role in organometallic chemistry. Palladium complexes exist in three easilyinterconvertible oxidation states, Pd(0), Pd(II), Pd(Ⅲ) and Pd(IV). Further more, the reactionconditions can be tuned by varying the ligand, base, oxidant, solvent, temperature, andadditives to optimize these oxidation states. On the other hand, Palladium-mediated organictransformations continue to be a fascinating area in organic synthesis as well asorganometallic chemistry because most palladium-based methodology proceeds stereo-andregioselectively in excellent yields under relatively mild reaction conditions and tolerates awide variety of functional groups. Up to now, palladium-catalyzed crossing reactions havebeen extensively applied in the syntheses of medicinal compounds and natural products andbeen shown to be one of the most powerful methods for the constructing new carbon-carbonand carbon-hetero bonds. This thesis expatiated upon certain studies aboutpalladium-catalyzed crossing reactions on basis of alkynes and the contents are as follows:In Chapter1, we introduced the reaction features of alkynes, and the progress on selectiveC-C and C-hetero bond formation via palladium-catalyzed crossing reactions on alkyns, andintroduced the significane of this research subject.In chapter2, δ-bromo-γ,δ-unsaturated carbonyls are readily prepared under mild reactionconditions via palladium-catalyzed bromoalkylation of alkynoates. In the reported systems,the terminators were often limited to alkenes with electron-withdrawing groups and themethods to quench the carbon-palladium bond of σ-vinylpalladium intermediate were oftenprotonolysis, β-H elimination or β-hetero elimination. A new and general protocol for thesynthesis of δ-bromo-γ,δ-unsaturated carbonyls by an bromopalladation/Heckcross-coupling/β-H elimination tandem process is described. This method is highly atomefficient, regio-and stereoselective and can tolerate a broad range of functional groups. Amechanism involving bromopalladation of alkyne, followed by insertion of allylic alcohol andallylic hydrogen shift is proposed. The shift of allylic hydrogen is the rate-limiting step in thisreaction.In chapter3, tetrasubstituted furans were synthesized in a fluorous biphasic system ofN,N-dimethylacetamide (DMA) and perfluorodecalin by palladium-catalyzed oxidation andcyclization of aromatic alkynes. Transition metal catalyzed cycloisomerization of unsaturated acyclic precursors to prepare multiply substituted furans has attracted much attention, butthese methods require the prior preparation of rather advanced starting materials, such asallenyl ketones, alkynyl ketones, or epoxides. We developed a novel method for synthesis oftetrasubstituted furans from readily available alkynes under mild reaction conditions via thepalladium catalyzed and ZnCl2promoted cyclization process. This protocol is also availablefor intramolecular oxidation and cyclization of1,6-diyne to form bicycle compound.In chapter4, a series of conjugated enynes were prepared by a simple Pd-catalyzedcross-coupling reaction of ethylenes and ethynyl bromides. Haloalkynes are highly valuablesynthons and widely used in synthetic organic chemistry for constructing complex organiccompounds due to their versatility. We developed another alternative cross-coupling reactionbetween a terminal alkene and a haloalkyne for synthesis of functionalized1,3-enyne in theabsence of any stabilizing ligands or special additives. The process is not only regio-andstereoselective, but also tolerant to several functional groups on both coupling partners.In chapter5, synthesis of4-benzyl substituted1,3-butadiene derivatives throughPd-catalyzed three-component coupling reaction of benzyl chlorides, alkynes, andmonosubstituted alkenes is described.1,3-diene unit is often found in natural products andpharmaceuticals, furthermore, and is useful as intermediate in multistep synthesis. Althoughthere are numerous methods for the preparation of1,3-butadiene derivatives, development ofgeneral and efficient routes to the regio-and stereoselective synthesis of benzylated1,3-dienes is still challenging. As a continuing interest in the coupling reactions on basis ofinternal alkynes, we developed a novel three-component coupling reaction for the synthesis of1,3-butadiene derivatives, which allows the rapid, efficient, and selective construction of aC(sp3)-C(sp2) bond and a C(sp2)-C(sp2) bond in a single reaction.