Iron-promoted C–C bond formation in the total synthesis of natural products and drugs

Abstract

Iron salts are inexpensive and almost innocuous; they are thus the promoters of choice, even in stoichiometric amounts, for the formation of carbon-carbon bonds in the backbone of complex molecules. This review encompasses the key role of iron complexes in the total synthesis of some natural products or pharmacologically important compounds.

Iron‐Catalyzed C−O Bond Activation: Opportunity for Sustainable Catalysis

“…[13][14][15][16] Seminals tudies by Fürstner et al on homogenous iron catalysis, reportedi n2 002, established the utility of oxygen-based electrophiles in C(sp 2 )ÀC(sp 3 )c ross-coupling (Scheme 2). [18,19] Moreover, in 2004, the same research group established the first examples of iron-Oxygen-based electrophiles have emerged as some of the most valuable cross-coupling partners in organic synthesis due to severalm ajor strategic and environmental benefits, such as abundance and potential to avoid toxic halide waste. The potential to chemoselectively cross-couple the CÀOb ond in the presence of an aryl halide has been elegantly exploited, including iterative iron-catalyzed cross-couplings in complex target synthesis (Scheme3).…”

An Iron‐Catalyzed Bond‐Making/Bond‐Breaking Cascade Merges Cycloisomerization and Cross‐Coupling Chemistry

“…[1][2][3][4][5][6] In this context, early work by our group has helped to demonstrate that this cheap,benign, readily available,a nd-for as urprisingly long time-underutilized element can serve as as ubstitute for palladium in various cross-coupling reactions. Not only does this new manifold lend itself to the extrusion of heteroelements (Z = O, NR), but it can even be used for the cleavage of activated C À Cbonds.The reaction likely proceeds via metallacyclic intermediates,t he iron center of whichg ains ate character before reductive elimination occurs.T he overall transformation represents ap reviously unknown merger of cycloisomerization and cross-coupling chemistry.I tp rovides ready access to highly functionalized1 ,3-dienes comprising astereodefined tetrasubstituted alkene unit, whichare difficult to make by conventional means.…”

“…[1][2][3][4][5][6] In this context, early work by our group has helped to demonstrate that this cheap,benign, readily available,a nd-for as urprisingly long time-underutilized element can serve as as ubstitute for palladium in various cross-coupling reactions. [1][2][3][4][5][6] In this context, early work by our group has helped to demonstrate that this cheap,benign, readily available,a nd-for as urprisingly long time-underutilized element can serve as as ubstitute for palladium in various cross-coupling reactions.…”

A Simple Synthesis of 1,3-Diphenylpropene

“…It is known that available iron(III) salts are effective catalysts in cross-coupling reactions of Grignard reagents with vinyl [9--12] and allyl halides [13,14]. Fe(acac) 3 the most commonly used in the synthesis of natural compounds [15,16] and drugs [17][18][19][20] is advantageously characterized by low hygroscopicity, good solubility, and ease of handling [21].The reaction of (E)-1,3-dichloropropene la with 3 equiv of PhMgBr in tetrahydrofuran in the presence of 3 mol % of Fe(acac) 3 afforded a mixture of (E)-and (Z)-isomers of 1,3-diphenylpropene 2a and 2b (E : Z = 92 : 8) in a 52% yield. The introduction of the most frequently used ligands like N,N,N,N-tetramethylethylenediamine (TMEDA) [22] or N-methylpyrrolidone (NMP) [10], the replacement of THF by diethyl ether and the use of FeCl 3 as the catalyst did not substantially increase the yield of the reaction product.…”

“…It is known that available iron(III) salts are effective catalysts in cross-coupling reactions of Grignard reagents with vinyl [9--12] and allyl halides [13,14]. Fe(acac) 3 the most commonly used in the synthesis of natural compounds [15,16] and drugs [17][18][19][20] is advantageously characterized by low hygroscopicity, good solubility, and ease of handling [21].…”