Enantioselective Iridium‐Catalyzed Hydrogenation of β,γ‐Unsaturated Carboxylic Acids: An Efficient Approach to Chiral 4‐Alkyl‐4‐aryl Butanoic Acids

Abstract

Sättigungsgefühle: Ein hoch enantioselektive Iridium‐katalysierte Hydrierung von β,γ‐ungesättigten Carbonsäuren liefert chirale 4‐Alkyl‐4‐arylbutansäuren (siehe Schema). Kurze Synthesen dreier natürlicher Sesquiterpene ausgehend von chiralen 4‐Alkyl‐4‐arylbutansäuren belegen das große Potenzial dieser neuen katalytischen asymmetrischen Reaktion.

Cobalt‐Catalyzed Enantioselective Negishi Cross‐Coupling of Racemic α‐Bromo Esters with Arylzincs

“…After coupling with vinylmagnesium bromide, hydroboration with 9‐BBN and oxidation with basic H 2 O 2 furnished primary alcohol ( R )‐ 9 (92 % ee , 75 % yield over 2 steps) . Finally, Dess–Martin oxidation and Wittig olefination with iso ‐propyltriphenylphosphonium iodide, followed by cleavage of the methyl ether with 2‐diethylaminoethanethiol and NaH gave ( R )‐xanthorrhizol with 92 % ee …”

Enantioselective Copper‐Catalyzed Conjugate Addition of Trimethylaluminum to β,γ‐Unsaturated α‐Ketoamides: Efficient Access to γ‐Methyl‐Substituted Carbonyl Compounds

“…In the end, we envisioned derivatization of A17 as we identified a m-methoxy-p-methylphenyl moiety in several natural products like (À)-mutisianthol, [19] (À)-7-hydroxycalamanene, [6b] (S)-xanthorrizol, [4] (S)-aristelegon A, [4] and (+)-heritol, [20] for example. These natural products could be obtained from A17 by using the synthetic route described in…”

“…For example, 1,4-adducts obtained by ACA to b,g-unsaturated a-ketoamides could be transformed into 4-aryl-4methylbutanoic acid, an important scaffold for the preparation of numerous acyclic and cyclic natural products ( Figure 2). [4] Indeed, our methodology would provide a new route to this chiral building block as only four asymmetric methods have been reported for its synthesis (hydrogenation of unsaturated carboxylic acid, [4] hydrovinylation of alkene, [5] isomerization of allylic alcohol [6] and enzymatic procedures [7] ).…”

Enantioselective Copper‐Catalyzed Conjugate Addition of Trimethylaluminum to β,γ‐Unsaturated α‐Ketoamides: Efficient Access to γ‐Methyl‐Substituted Carbonyl Compounds

“…For example, 1,4‐adducts obtained by ACA to β,γ‐unsaturated α‐ketoamides could be transformed into 4‐aryl‐4‐methylbutanoic acid, an important scaffold for the preparation of numerous acyclic and cyclic natural products (Figure 2). 4 Indeed, our methodology would provide a new route to this chiral building block as only four asymmetric methods have been reported for its synthesis (hydrogenation of unsaturated carboxylic acid,4 hydrovinylation of alkene,5 isomerization of allylic alcohol6 and enzymatic procedures7).…”

“…In the end, we envisioned derivatization of A17 as we identified a m ‐methoxy‐ p ‐methylphenyl moiety in several natural products like (−)‐mutisianthol,19 (−)‐7‐hydroxycalamanene,6b ( S )‐xanthorrizol,4 ( S )‐aristelegon A,4 and (+)‐heritol,20 for example. These natural products could be obtained from A17 by using the synthetic route described in Scheme .…”