Transition Metal Catalyzed Cross-couplings Of Activated Alkyl Halides

Transition metal catalyzed organic synthesis is the frontier area in chemicalcommunity. As one of the most powerful tool, cross-coupling is the efficient methodfor constructing C-C and C-heteroatom bonds. Up to now, aryl or alkenyl halides arethe major electrophiles employed in cross-couplings. As another important type ofelectrophile, alkyl halides has yet less been applied. In this thesis, a brief introductionof cross-couplings was first reviewed. The development of alkyl halides relatedcross-couplings was then surveyed in details. The research work of this thesis wasfocused on the cross-couplings of activated alkyl halides. Details are as followings:1. First, palladium enolate and benzylpalladium complexes were synthesizedvia the direct oxidative addition of deshyl chloride and benzyl chloride with Pd(0),respectively. Palladium enolate complex was determined to be a simplex carbonbound palladium enolate by VT NMR and X-ray analysis. Benzylpalladium complexwas characterized to have a benzyl3coordination to palladium center. The palladiumenolate is unstable in solution and will gradually decompose to homo-coupled productand a half of Pd(II) and a half of Pd(0). The mechanism of this decomposition wasstudied in detail. The dimerization of the palladium enolate is the key step. Then, thedisproportionation of the dimer releases a half of Pd(II) species anddiorganopalladium intermediate. The bulky Csp3-Csp3reductive elimination affordsthe homo-coupled product and a half of Pd(0) species.2. Based on the decomposition of the palladium enolate, activated zinc wasapplied as the reductant to achieve Pd-catalyzed reductive coupling of-carbonylsecondary alkyl halides. Tetraaryl1,4-diketones were easily obtained. Mechanisticstudy showed that the insight of the reductive coupling is actually the cross-couplingof-carbonyl secondary alkyl halides with in situ formed zinc enolate. Then, zincenolate was prepared to cross-couple with a different-carbonyl secondary alkylhalides to achieve unsymmetric2,3-diaryl-1,4-diketones in the presence of palladiumcatalyst.3. The cross-coupling of-carbonyl secondary alkyl halides with arylboronicacids was achieved in the presence of Ni(PPh3)4as the catalyst. A variety of-arylcarbonyls were constructed.-Bromoesters,-bromoamides and-bromoketoneswere well introduced to couple with a number of arylboronic acids.-Carbonyl alkylchlorides are also suitable coupling partners. Water is also an essential factor topromote the coupling reaction. The ideal ratio of water to K3PO4is1.5:1. Free radicalcapture experiments showed that a radical process might be involved in this coupling reaction. Ni(I), Ni(II) and Ni(III) species possibly participated in the catalytic cycle.4. Based on the mechanistic investigation of Ni-catalyzed cross-coupling of-carbonyl alkyl halides with arylboronic acids, a Heck-type alkenylation ofsecondary and tertiary alkyl bromides were accomplished in the presence ofNi(PPh3)4/dppp as the catalyst. This work provides a novel method for the synthesisof-alkenyl carbonyls. A novel radical process involving Ni(I)/Ni(II) in the catalyticcycle was proposed for this transformation, which is different from the classicPd-catalyzed Heck reaction.5. Based on the study of benzylpalladium complex, a Pd-catalyzed oxidativeesterification was achieved by using benzyl chloride as the oxidant. In the presence ofPdCl2(PPh3)2as the catalyst, a variety of primary alcohols were selectively convertedto the corresponding esters. Mechanistic study exhibited that benzyl group is essentialfor the selective esterification. Based on the results, a concept of covalent ligandeffect was stated in this thesis. The covalent benzyl effect was later applied to thePd-catalyzed oxidative cross-esterification of aldehydes with alcohols. In addition,replacement of benzyl chloride by the greenest oxidant oxygen was then investigatedto achieve oxidative esterification of benzyl alcohols with aliphatic ones.