A general synthesis of symmetrically disubstituted ureas and trisubstituted ureas by direct Pd-catalyzed oxidative carbonylation of primary amines or of a mixture of a primary and a secondary amine, respectively, with unprecedented catalytic efficiencies for this kind of process, is reported. Reactions are carried out at 90-100 degrees C in DME as the solvent in the presence of PdI(2) in conjunction with an excess of KI as the catalytic system and under 20 atm of a 4:1 mixture of CO and air. In some cases, working in the presence of an excess of CO(2) (40 atm) in addition to CO and air (60 atm total) had a beneficial effect on substrate reactivity and product yield. Cyclic five-membered and six-membered ureas were easily formed from primary diamines. The methodology has been successfully applied to the synthesis of pharmacologically active ureas, such as those deriving from alpha-amino esters or urea NPY5RA-972, a potent antagonist of the neuropeptide Y5 receptor.
Terminal alkyne dicarbonylation can be readily effected under mild conditions b y treating alkynes with carbon monoxide and alcohols or water at 25-80°C in the presence of Pdlp, KI and air, with unprecedented catalytic efficiency. Dicarbonylated products are mainly maleic esters or acids and their ring-chain tautomers. The latter are formed to a large extent at room temperature. Reaction pathways are discussed.Dicarbonylation of alkynes with carbon monoxide has been known for several years,' but even the most recent literature reports methods which are not completely satisfactory particularly from the standpoint of catalytic efficiency. However, alkyl-or aryl-maleic esters and acids are interesting products, which can be used as monomers for polymerization, so an efficient procedure to prepare these compounds is a useful target. We now report such a procedure, which affords high yields of alkyl-or aryl-maleic esters and acids under mild conditions. A preliminary account, limited to prop-2-ynyl alcohol, was published r e c e n t l ~. ~
Recent advances in the field of oxidative carbonylation reactions leading to carbonylated heterocyclic derivatives are presented (coverage: 2006 to the beginning of 2012).
A general and facile synthesis of furans, based on Pd(II)-catalyzed cycloisomerization of (Z)-2-en-4-yn-1-ols, is described. Cycloisomerization reactions are carried out at 25−100 °C in the presence
of a very simple catalytic system, consisting of K2PdI4, under essentially neutral conditions. This
new methodology is very versatile and can be applied to the synthesis of a variety of substituted
furans, including particularly fragile, naturally occurring furans such as rosefuran. Efficient
synthetic approaches for the regioselective synthesis of suitably substituted (Z)-2-en-4-yn-1-ols have
been developed.
A general and convenient synthesis of substituted quinolines by regioselective copper- or palladium-catalyzed 6-endo-dig cyclization-dehydration of 1-(2-aminoaryl)-2-yn-1-ols is reported. The crude substrates were easily obtained by the Grignard reaction between the appropriate alkynylmagnesium bromide and 2-aminoaryl ketones and could be used without further purification for the subsequent cyclization step. Heteroannulation reactions were carried out in MeOH or DME as the solvent at 60 or 100 degrees C in the presence of CuCl(2) or PdX(2) (in conjunction with 10 equiv of KX, X = Cl, I) as the catalyst to afford the quinoline derivatives in good to excellent isolated yields based on starting 1-(2-aminoaryl)-2-yn-1-ols (66-90%).
[reaction: see text] 2-Oxazolidinones 2 are obtained in excellent yields (up to 100%) and with unprecedented catalytic efficiencies (up to 2000 mol of product/mol of catalyst used) by direct PdI2/KI-catalyzed oxidative carbonylation of the readily available 2-amino-1-alkanols 1. Reactions are carried out in MeOH as the solvent at 100 degrees C using a 1/6/5 CO/O2/air mixture (60 atm total pressure at 25 degrees C).
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