Catalytic Asymmetric Conjugate Reduction

Abstract

Enantioselective reduction reactions are privileged transformations for the construction of trisubstituted stereogenic centers. While these include established synthetic strategies, such as asymmetric hydrogenation, methods based on the enantioselective addition of hydridic reagents to electrophilic prochiral substrates have also gained importance. In this context, the asymmetric conjugate reduction (ACR) of α,β-unsaturated compounds has become a convenient approach for the synthesis of chiral compounds with trisubstituted stereocenters in α-, β-, or γ-position to electron-withdrawing functional groups. Because such activating groups are diverse and amenable of further derivatizations, ACRs provide a general and powerful synthetic entry towards a variety of valuable chiral building blocks. This Review provides a comprehensive collection of catalytic ACR methods involving transition-metal, organic, and enzymatic catalysis since its first versions dating back to the late 1970s.

Biocatalytic approaches for a more sustainable synthesis of sandalwood fragrances

“…Besides the stereoselective reduction of prochiral enones or enals ( 4–5 ), 35 OYE2 has demonstrated its superiority in terms of chemoselectivity compared to other catalytic procedures. 5 b Indeed, in the synthesis of substrate 5c (Sandalore® precursor) we faced the problem of hydrogenating the α,β-unsaturated ketone 6 to ketone 8 preserving the campholenic double bond.…”

“…Indeed, to our knowledge, these catalysts have never been combined in a one-pot two hydrogenations-step capable of stereoselectively reducing enals or enones into the corresponding alcohols. 35 Lastly, the bioreduction is undoubtedly a safer process, as clearly indicated by the higher number of hazards and risks typically associated with the hydrogenations and the hydridebased reductions.…”

Co(Salox)‐Catalyzed Enantioselective Reduction of α,β‐Unsaturated Esters

“…Asymmetric Conjugate Reductions (ACRs) are convenient synthetic tools for controlling the formation of stereocenters in β-position with respect to a variety of electron-withdrawing groups. [1][2][3][4][5][6] These have become a suitable alternative to hydrogenations with pressurized H 2 gas or conjugate additions with organometallic reagents due to their operational simplicity and high efficiency. Among other transition metals, Cu plays a major role in this context, with LCuÀ H complexes of chiral phosphines being the state of the art for the ACR of esters, [7][8][9][10][11][12] amides, [13] ketones, [14][15][16][17] nitriles, [18][19][20][21] and many other EWGs.…”

“…Asymmetric Conjugate Reductions (ACRs) are convenient synthetic tools for controlling the formation of stereocenters in β‐position with respect to a variety of electron‐withdrawing groups [1–6] . These have become a suitable alternative to hydrogenations with pressurized H 2 gas or conjugate additions with organometallic reagents due to their operational simplicity and high efficiency.…”

Unexpected rapid P-stereomutation of phosphine oxides catalysed by chlorophosphonium salts

“…Enantioselectivity is considered as one of the key goals in synthetic chemistry and often requires careful adjustment of conditions. Stereoselective reactions and novel approaches to chiral materials attract immense attention from the organic, 1 inorganic 2 and supramolecular 3 communities. Rapid stereomutation of an intermediate can be critical to many successful stereoselective strategies 4 but must be avoided for the product as it leads to loss of chiral information.…”