A new chiral ligand for the asymmetric conjugate addition of organocopper reagents to enones

Abstract

cussions. The financial help of Rh6ne-Poulenc Company through a grant to S.M. is also greatly appreciated. 1r(13) Typical procedure: To a suspension of CUI (476 mg; 2.5 mmol) in T H F (40 mL) is added ligand 1 (3.4 mL of a 1.5 N solution in toluene; 5.1 mmol) at -30 OC. The temperature is allowed to rise, and solubilization is usually observed around IO OC. After stirring for 15 min, the solution is cooled to -40 OC and nBuLi (1.45 mL of a 1.6 M solution in hexane; 2.3 mmol) is added. The solution, which turns yellow, is warmed for IS min at -5 OC and then cooled again to 78 OC, and 2-cyclohexenone 7 (200 & 2 mmol) in T H F ( 5 mL) is introduced. The mixture is then slowly warmed to -30 OC (in 1 h) and stirred until the disappcarance of 7. Hydrolysis was carried out with 15 mL of 5 N HCI, and stirring is continued in the open air for 1 h in order to hydrolyze the ligand completely. The aqueous phase is extracted with two 1 0 0 " portions of ether, and the combined organic phases were then washed twice with NH,OH in order to remove the copper salts. The solvents were removed in vacuo, and the crude product was treated with (R,R)-2,3-butanediol in a Dean-Stark trap.* The final ketal 9 was purified by flash column chromatography and then by Kugelrohr distillation.

Asymmetric Organocopper Chemistry: Cu-Catalyzed Conjugate Addition and Allylic Substitution

“…5,6 Although other ligand types have been disclosed, the ones based on phosphorus are the most effective. Most ligands are monodentate, but some are bidentate, either P,P or P,N.…”

“…4 Later on, Alexakis introduced, in 1991, the use of chiral trivalent phosphorus ligands and demonstrated their efficiency. 5 For catalytic amount of copper salt, and therefore chiral ligand, the same authors showed that dialkylzinc reagents were more appropriate than the classical use of Grignard reagents. 6 It followed that in the last 6-7 years, a tremendous effort has been put, by more and more authors, in disclosing more and more efficient chiral ligands (>350 !…”

“…However, the early studies revealed that higher enantioselectivities were obtained with a 2:1 ratio of ligand to copper, 5,6 and most authors systematically used these conditions. In fact, we observed that the enantioselectivity remains roughly the same with as little as a 1.2:1 ratio.…”

Copper-mediated asymmetric transformations

“…Until 1993, all authors have relied upon the use of Grignard reagents, whereupon we introduced the idea of using diorganozinc reagents instead [4]. The needed chiral information was brought by a trivalent phosphorus ligand, a type of chiral ligand we also introduced in organocopper chemistry, in 1991 [5]. This combination of reagents has, since then, found a widespread use (Scheme 3).…”

Peptidic Amidomonophosphane Ligand for Copper‐Catalyzed Asymmetric Conjugate Addition of Diorganozincs to Cycloalkenones

“…[8] Further brilliant successes have also been continuously reported by using dialkylzinc reagents as sources of alkyl nucleophiles, which are characterized by the use of a phosphorus-based ligand for copper. [9,10] Since the development of a phosphoroamidite by Alexakis group, [11,12] binaphthol-based phosphorus ligands have been demonstrated to be really effective giving over 90 % ee by the endeavors of the Feringa [13] and Zhang [14] groups. Highly efficient phosphane ligands were also developed by Imamoto [15] and Hoveyda.…”