Catalytic asymmetric carbon–carbon bond formation using alkenes as alkylmetal equivalents

Abstract

Catalytic asymmetric conjugate addition reactions with organometallic reagents are powerful reactions in synthetic chemistry. Procedures that use non-stabilized carbanions have been developed extensively, but these suffer from a number of limitations that prevent their use in many situations. Here, we report that alkylmetal species generated in situ from alkenes can be used in highly enantioselective 1,4-addition initiated by a copper catalyst. Using alkenes as starting materials is desirable because they are readily available and have favourable properties when compared to pre-made organometallics. High levels of enantioselectivity are observed at room temperature in a range of solvents, and the reaction tolerates functional groups that are not compatible with comparable methods-a necessary prerequisite for efficient and protecting-group-free strategies for synthesis.

Asymmetric Conjugate Additions and Allylic Alkylations Using Nucleophiles Generated by Hydro‐ or Carbometallation

“…[61,62] This generally gives high enantioselectivity in additions to cyclic enones at room temperature, and as shown in Scheme 24, tolerates ar ange of functional groups.T he procedure is generally compatible with different solvents and additives, and can be used on ag ram scale with no loss of enantioselectivity or yield. [61,62] This generally gives high enantioselectivity in additions to cyclic enones at room temperature, and as shown in Scheme 24, tolerates ar ange of functional groups.T he procedure is generally compatible with different solvents and additives, and can be used on ag ram scale with no loss of enantioselectivity or yield.…”

Development of Axially Chiral Cyclo‐Biaryldiol Ligands with Adjustable Dihedral Angles

“…Given that phosphoramidites of axially chiral biaryldiols are privileged ligandsi na symmetric catalysis, [15] we prepared twenty phosphoramidite ligands (Table 4) according to the previous procedures (see the Supporting Information for details). [16] An interesting reaction, copper-catalyzeda symmetric carbon-carbon bond formation using alkenes as alkylmetal equivalents, developedb yF letcher and co-workers [16] was selected as the modelt oe valuatet he effects of the known ligands ando ur newly developed biaryldiol phosphoramidites. As shown in Table 4, treatment of phosphoramidite ligand with (CuOTf) 2 PhH led to the formationo ft heir respective complex (ligand-Cu) at room temperature under argon atmosphere;m eanwhile, reaction of alkene 16 a with Cp 2 ZrHCl gave addition product 17 a in another flask under the similar conditions.…”

Acyclic quaternary centers from asymmetric conjugate addition of alkylzirconium reagents to linear trisubstituted enones

“…13 Reacting an alkene with the Schwartz reagent (Cp 2 ZrHCl) forms alkylzirconium species in situ which can undergo ACA without the need for cryogenic conditions. These methods allow introduction of reasonably complex alkyl nucleophiles that are normally incompatible with premade organometallic nucleophiles.…”

“…We reported building tertiary 13 and quaternary centers 15 by addition to cyclic α,β-unsaturated ketones. 16 In acyclic substrates, it is much more difficult to obtain high enantioselectivity, presumably due to interconversion between s- cis and s- trans conformers.…”