Modern Synthetic Methods for the Stereoselective Construction of 1,3-Dienes

Abstract

The 1,3-butadiene motif is widely found in many natural products and drug candidates with relevant biological activities. Moreover, dienes are important targets for synthetic chemists, due to their ability to give access to a wide range of functional group transformations, including a broad range of C-C bond-forming processes. Therefore, the stereoselective preparation of dienes have attracted much attention over the past decades, and the search for new synthetic protocols continues unabated. The aim of this review is to give an overview of the diverse methodologies that have emerged in the last decade, with a focus on the synthetic processes that meet the requirements of efficiency and sustainability of modern organic chemistry.

A Dual CuH- and Pd-Catalyzed Stereoselective Synthesis of Highly Substituted 1,3-Dienes

“…8 The utility of conjugated dienes has been demonstrated in a variety of critical synthetic processes, including: cycloadditions, 9-10 hydrofunctionalizations, [11][12][13] and difunctionalizations. [14][15][16] The stereochemical outcome of these methods is typically influenced by the olefin geometry of the 1,3-diene substrate. 10,14,15 Accordingly, methods to access substituted 1,3-dienes in a stereoselective manner are paramount for their use in fine chemical synthesis.…”

“…10,14,15 Accordingly, methods to access substituted 1,3-dienes in a stereoselective manner are paramount for their use in fine chemical synthesis. 8,16 While various methods exist for the synthesis of E,Edienes, [16][17][18] a general, highly stereoselective process to produce Zdienes is desirable.…”

“…Due to the utility of 1,3-dienes in organic synthesis, a variety of strategies to access these compounds have been developed. 8,16 Olefination of carbonyl compounds with stoichiometric allyl nucleophiles has been widely employed in the synthesis of conjugated dienes, [19][20][21][22][23][24][25][26] however, the products are generally obtained as inseparable E/Z-mixtures (Figure 1A). [26][27] Although considerable advances have been made towards stereoselective olefination of carbonyl substrates, most methods to access 1,3-dienes result in the E,E-isomer.…”

Photoinduced Copper‐Catalyzed Asymmetric Three‐Component Coupling of 1,3‐Dienes: An Alternative to Kharasch–Sosnovsky Reaction

“…1,3-Dienes and derivatives have been extensively investigated as allyl sources in organic synthesis owing to their readily availability and ambivalent regioselectivity involving either a1,2-or 1,4-difunctionalization pattern. [6] In addition to their broad applications in numerous ionic reactions acting on the carbon-carbon double bonds, [7] their unique structural properties render 1,3-dienes to be competent radical trapping reagents. [8] Theg roups of Zhang, [9] Glorius, [10,11] Gevorgyan, [12] and Shi [13] have made seminal contributions to this area.…”

Stereospecific Synthesis of Conjugated Dienes by Carbenoid Eliminative Cross‐Coupling Using Lithiated Allylic Carbamates

“…Conjugated diene motifs are encountered in all manner of useful compounds, including many biologically significant molecules. [1] For example, the potent cytotoxic agent callystatin A (1), a representative polyketide of marine origin, [2] contains two conjugated diene domains: an (E,Z)-configured diene from C6-C9 and an (E,E)-configured diene from C12-C15 (Figure 1). In each case, one of the double bonds comprising the conjugated diene unit is 1,2-disubstituted, but the adjacent alkene is trisubstituted, which makes addressing the stereocontrolled synthesis of such dienes, which are actually quite common, [3] challenging.…”