ABSTRACT
A straightforward and efficient alumination of functionalized arenes by using the frustrated Lewis pair Et3 Al and TMPMgClâ LiCl (TMP=2,2,6,6-tetramethylpiperidyl) has been developed. In particular, halogenated electron-rich aromatics can be smoothly functionalized by using the frustrated Lewis pair Et3 Al and TMPMgClâ LiCl. Compared with previously described alumination methods, this procedure avoids extensive cooling and the need for an excess of base. This in situ procedure has proven to be most practical and allows for regio- and chemoselective metalation of a wide range of aromatics with sensitive functional groups (CONEt2 , CO2 Me, CN, OCONMe2 ) or halogens (F, Cl, Br, I). The resulting aromatic aluminates, which were characterized by using NMR spectroscopy, were subjected to allylations, acylations, and palladium-catalyzed cross-coupling reactions after transmetalation to zinc. It was shown that the nature of the Zn salt used for transmetalation is crucial. Thus, compared with ZnCl2 (2â equiv), the use of Zn(OPiv)2 (2â equiv; OPiv=pivalate) allows the subsequent quenching reactions to be performed with only a slight excess of electrophile (1.2â equiv) and provides interesting functionalized aromatics in good yields.
ABSTRACT
A practical zinc insertion starting from cheap commercial zinc powder and TMPCl (1-chloro-2,2,6,6-tetramethylpiperidine) allows a fast and efficient synthesis of the zinc base TMPZnCl·LiCl under mild conditions in high yields. This base is kinetically highly active and was used for the regio- and chemoselective functionalization of dibromodiazines (pyridazines and pyrazines).
Subject(s)
Hydrocarbons, Chlorinated/chemistry , Hydrocarbons, Chlorinated/chemical synthesis , Lithium/chemistry , Organometallic Compounds/chemical synthesis , Piperidines/chemistry , Pyridazines/chemical synthesis , Zinc/chemistry , Combinatorial Chemistry Techniques , Molecular Structure , Organometallic Compounds/chemistry , Pyridazines/chemistry , StereoisomerismABSTRACT
A handsome couple: Through the use of the simple Pd catalyst [Pd(tmpp)(2)Cl(2)] (tmpp = tris(2,4,6-trimethoxyphenyl)phosphine) and THF/DMF as solvent, various aryl-, heteroaryl-, benzyl- and alkylaluminum reagents can be readily cross-coupled with aryl or heteroaryl iodides, bromides, and nonaflates, and in special cases even with chlorides and triflates. This cross-coupling tolerates free NH(2) groups, aldehydes, ketones, esters, and nitro functions.
Subject(s)
Aluminum/chemistry , Organometallic Compounds/chemistry , Organometallic Compounds/chemical synthesis , Palladium/chemistry , Catalysis , Molecular StructureABSTRACT
The metalation of various SEM-protected functionalized indazoles with TMP(2)Zn provides 3-zincated indazoles which undergo palladium-catalyzed Negishi cross-couplings in good yields.
Subject(s)
Indazoles/chemistry , Iodides/chemistry , Piperidines/chemistry , Zinc/chemistry , Catalysis , Palladium/chemistry , StereoisomerismABSTRACT
We have designed a new sequential carbocupration and sulfur-lithium exchange that leads stereo- and regioselectively to trisubstituted alkenyllithiums. Subsequent trapping with various electrophiles yields tetrasubstituted olefins with good control of the double-bond geometry (E/Z ratio up to 99:1). The novel sulfur-lithium exchange could be extended to the stereoselective preparation of Z-styryl lithium derivatives with almost complete retention of the double-bond geometry.
ABSTRACT
A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF by using (TMP)(2)Mg2 LiCl (TMP=2,2,6,6-tetramethylpiperamidyl) in the presence of ZnCl(2). The possible pathways of this metalation procedure as well as possible reactive intermediates are discussed. This experimental protocol expands the tolerance of functional groups and allows an efficient zincation of sensitive heterocycles such as quinoxaline or pyrazine. The zincated arenes and heteroarenes react with various electrophiles providing the expected products in 60-95 % yield.
