Heck‐Like Reactions Involving Heteroatomic Electrophiles

Abstract

Since the discovery of the Heck reaction in the early seventies, this reaction has become a powerful tool in synthetic organic chemistry. By employing heteroatomic instead of traditional carbon electrophiles, the Heck reaction shows an intriguing flexibility. These "hetereoatomic-Heck reactions" reinvigorate the area, offering new routes to highly useful synthetic precursors and structural motifs present in biologically active compounds. This microreview focuses on early developments leading to the heteroatomic-Heck reactions (silyl-Heck, boryl-Heck and intramolecular aza-Heck), current state of the emerging area, as well as that of a few related processes.

Synthesis of N−H Bearing Imidazolidinones and Dihydroimidazolones Using Aza‐Heck Cyclizations

“…Ab road range of functional groups are also compatible with the cyclization, including ethers (6,9,21,23,29), esters (8,33), isolated alkenes (35), aromatic halogens (10)(11)28), trifluoromethyl groups (7), protic functionalities (15-16, 20, 24, 26, 33), and arange of heterocycles (17)(18)(26)(27). Increased substitution on the 5-membered ring, however,i sw ell tolerated (24), as is substitution on the alkyl group (25).…”

“…Recently,Heck-type cyclizations of nitrogen electrophiles have emerged as ap owerful and flexible strategy for preparing nitrogen-containing heterocycles, [10,11] and we have shown that unsaturated lactams bearing free NÀH groups can be prepared via the palladium-catalyzed cyclization of O-phenyl hydroxamates onto pendant alkenes. [12] We hypothesized that the synthesis of N À Hb earing imidazolidinones from N-phenoxy ureas might also be possible,w hich would allow for the direct synthesis of unprotected imidazolidinone scaffolds bearing unsaturation vicinal to one of the nitrogen centers.H erein, we describe the successful realization of that goal, and report conditions for the preparation of unsaturated, unprotected imidazolidinones using an aza-Heck strategy.U sing easily accessed starting materials,a nd commercially available catalytic components,w es how that the reaction enjoys broad functional group tolerance and is highly flexible with respect to accessible ring topologies.Further,by the addition of iodide additives,i someric dihydroimidazolones can also be prepared from the same starting materials.…”

“…Themodel substrate 4 was isolated in 84 %yield, and closely related derivatives were prepared with similar efficiency (6)(7)(8)(9)(10)(11). Themodel substrate 4 was isolated in 84 %yield, and closely related derivatives were prepared with similar efficiency (6)(7)(8)(9)(10)(11).…”

Synthesis of N−H Bearing Imidazolidinones and Dihydroimidazolones Using Aza‐Heck Cyclizations

“…Recently, Heck-type cyclizations of nitrogen electrophiles have emerged as a powerful and flexible strategy for preparing nitrogen-containing heterocycles, [10],[11] and we have shown that unsaturated lactams bearing free N–H groups can be prepared via the palladium-catalyzed cyclization of O -phenyl hydroxamates onto pendant alkenes. [12] We hypothesized that the synthesis of N–H bearing imidazolidinones from N -phenoxyureas might also be possible, which would allow for the direct synthesis of unprotected imidazolidinone scaffolds bearing unsaturation vicinal to one of the nitrogen centers.…”

“…Thes cope of reaction was next investigated (Scheme 2). Themodel substrate 4 was isolated in 84 %yield, and closely related derivatives were prepared with similar efficiency (6)(7)(8)(9)(10)(11). More substituted alkenes,i ncluding tetrasubstituted alkene,also participate well in the reaction (12)(13)(14).…”