Synthetic Routes towards Multifunctional Cyclopentadienes

Abstract

Cyclopentadiene, and more importantly its functionalized derivatives, are a cornerstone of synthetic chemistry. Nowadays, they find applications in (chiral) catalysis, as ligands for organometallic complexes with potential diagnostic and therapeutic applications, and many more. This Minireview highlights the progress that has been made in the development of flexible and robust synthetic routes towards multifunctional cyclopentadienes in the last 20 years.

Theoretical Studies on the Mechanism of the Formation of Cyclopentadienes and Dihydropyridazines

“…Cyclopentadienes (Cps) are important, as synthetic intermediates, in the field of organic and organometallic chemistry. [1][2][3][4][5] Cps are well-known as precursors to build transition-metal complexes with Cp-type ligands in the field of coordination chemistry [6][7][8][9][10] and also as diene units to form cyclic heterocycles with the help of inter-and intramolecular Diels-Alder (DA) reactions. [11][12][13][14] Despite their importance, it is very difficult to synthesise substituted Cps, due to the instability of the parent Cp and the easy migration of the endocyclic double bonds.…”

“…As a result, there is no straightforward method for the functionalisation of Cps. [15][16][17][18][19][20][21][22][23][24] Although the synthesis of various Cps remains challenging, considerable efforts were devoted towards the functionalised Cps, [1,[25][26][27][28][29][30][31][32][33][34][35][36] particularly by 4π-electrocyclisation. [27,28] Substituted Cps can also be formed directly by nickel catalysed [3 + 2] cycloaddition reaction.…”

Convenient Cyclopentadiene Modifications for Building Versatile (Radio‐)Metal Cyclopentadienyl Frameworks

“…Some Cp structures are prone to undergo Diels-Alder dimerization. Functionalization of cyclopentadiene depends frequently on the use of different starting materials from multi-step syntheses, [6] rendering them costly and time consuming. All these reasons make the synthesis and biological evaluation of new 99m Tc cytectrenes not very attractive, which hinders the development of new radiopharmaceutical compounds of this class.…”

“…Based on the work of Hatanaka et al and previous work of our group, [6,8] Cp 1 was synthesized from the α-bromoketone 2 and the Wittig salt 3 under alkaline conditions in 76 % yield. Bromoketone 2 was synthesized in 65 % yield by treating 4 with Br 2 at low temperatures.…”

Two is better than one: difunctional high-affinity PSMA probes based on a [CpM(CO)3] (M = Re/99mTc) scaffold

“…Cyclopentadiene (Cp) ligands are ideal chelators for the Re/ 99m Tc(I) tricarbonyl system due to their small size, high stability of the formed complexes, and the possibility to functionalize them with one or more targeting units. [10] By using a multifunctional Cp as both the metal-coordinating moiety and as the linker to the two PSMA-ligands the usually large and bulky chelating part of the compound can be minimized to only a fraction of the resulting complex. The two ester-groups of 1 are sufficiently different in reactivity on the free Cp to allow for step-wise hydrolysis and functionalization with amine-bearing functionalities.…”