Arylamine synthesis
AssigneeMassachusetts Institute of Technology
InventorsJohn P. Wolfe, Jens Ahman, Joseph P. Sadighi, Robert A. Singer, Stephen L. Buchwald
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Abstract
The present invention provides a method for the preparation of a wide range of primary arylamines. The arylamines are prepared in two efficient, straightforward transformations: 1) an activated aryl group and an imine group are combined, in the presence of a transition metal catalyst, under conditions wherein the transition metal catalyst catalyzes the formation of a carbon-nitrogen bond between the activated carbon of the arene and the imine nitrogen; and 2) the resulting N-aryl imine is transformed, via any of a number of standard protocols, to the primary arylamine. The method of the invention may also be exploited in the preparation of vinylamines.
Claims88
The method depicted in Scheme 1:
- wherein:
- Ar is selected from the group consisting of optionally substituted monocyclic and polycyclic aromatic and heteroaromatic moieties;
- X is selected from the group consisting of Cl, Br, I, —OS(O)2halogen, —OS(O)2alkyl, and —OS(O)2aryl;
- the transition metal catalyst comprises a transition metal selected from Groups 5-12 of the periodic table;
- R is selected from the group consisting of hydrogen, trialkylstannyl, triarylstannyl, trialkylsilyl, triarylsilyl, lithium, sodium, potassium, magnesium halide, calcium halide, —B(OH)2, and groups that are replaced by hydrogen under the reaction conditions;
- R1 and R2, each independently represent hydrogen, or an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl group, or —(CH2)m—R8;
- or R1 and R2 taken together form an optionally substituted ring;
- the base is selected from the group consisting of alkoxides, carbonates, amides, phosphates, fluorides;
- R8 represents an optionally substituted aryl, cycloalkyl, cycloalkenyl, heterocycle or polycycle;
- and
- m is an integer in the range of 0 to 8 inclusive.
The method depicted in Scheme 3:
- wherein:
- X is selected from the group consisting of Cl, Br, I, —OS(O)2halogen, —OS(O)2alkyl, and —OS(O)2aryl;
- the transition metal catalyst comprises a transition metal selected from Groups 5-12 of the periodic table;
- R is selected from the group consisting of hydrogen, trialkylstannyl, triarylstannyl, trialkylsilyl, triarylsilyl, lithium, sodium, potassium, magnesium halide, calcium halide, —B(OH)2, and groups that are replaced by hydrogen under the reaction conditions;
- R1 and R2, each independently represent hydrogen, or an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl group, or —(CH2)m—R8;
- or R1 and R2 taken together form an optionally substituted ring;
- R′ is selected, independently for each occurrence, and as valence and stability permit, from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, formyl, acyl, amino, acylamino, amido, amidino, cyano, nitro, sulfonyl, sulfoxido, sulfate, sulfonate, sulfamoyl, sulfonamido, phosphoryl, phosphonate, phosphinate, —(CH2)m—R8, —(CH2)m—OH, —(CH2)m—O-alkyl, —(CH2)m—O-alkenyl, —(CH2)m—O-aryl, —(CH2)m—O—(CH2)m—R8, —(CH2)m—SH, —(CH2)m—S-alkyl, —(CH2)m—S-alkenyl, —(CH2)m—S-aryl, —(CH2)m—S—(CH2)m—R8, a solid support, and a polymeric support;
- the base is selected from the group consisting of alkoxides, carbonates, amides, phosphates, and fluorides;
- R8 represents an optionally substituted aryl, cycloalkyl, cycloalkenyl, heterocycle or polycycle;
- and
- m, independently for each occurrence, is an integer in the range of 0 to 8 inclusive.
Dependencies are inferred from the claim text.