Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones

BINOL: A Versatile Chiral Reagent

Catalytic enantioselective allylation of carbonyl compounds and imines.

Chiral tertiary alcohols and R-tertiary amines are important building blocks of naturally occurring and artificial biologically active molecules. Although there are catalytic asymmetric oxidation and amination reactions to access these chiral building blocks, the catalytic asymmetric addition of carbon nucleophiles to ketones and ketimines, which can simultaneously construct a carbon skeleton and tetrasubstituted stereogenic center, is synthetically more efficient (Scheme 1). Realizing the catalytic asymmetric addition to ketones and ketimines (tetrasubstituted carbon synthesis), however, is generally more challenging than addition to aldehydes or aldimines (trisubstituted carbon synthesis) for two main reasons: (1) ketones and ketimines are significantly less reactive than aldehydes and aldimines; (2) enantio-face differentiation of ketones and ketimines is more difficult due to the smaller steric and electronic differences between the two substituents on prochiral carbons. Therefore, asymmetric catalysts that promote C-C bond-formation to ketones and ketimines should have high catalyst activity and enantioselectivity.

Asymmetric Synthesis of Tertiary Alcohols and α-Tertiary Amines via Cu-Catalyzed C−C Bond Formation to Ketones and Ketimines

There is a need for the preparation of enantiomerically pure compounds for various applications. An efficient approach to achieve this goal is asymmetric catalysis. The chiral catalyst is usually prepared from a chiral auxiliary, which itself is derived from a natural product or by resolution of a racemic precursor. The use of non-enantiopure chiral auxiliaries in asymmetric catalysis seems unattractive to preparative chemists, since the anticipated enantiomeric excess (ee) of the reaction product should be proportional to the ee value of the chiral auxiliary (linearity). In fact, some deviation from linearity may arise. Such nonlinear effects can be rich in mechanistic information and can be synthetically useful (asymmetric amplification). This Review documents the advances made during the last decade in the use of nonlinear effects in the area of organometallic and organic catalysis.

Nonlinear Effects in Asymmetric Catalysis

A simple procedure is reported for the catalytic asymmetric allylation of ketones, utilizing titanium tetraisopropoxide, BINOL, 2-propanol additive, and tetraallylstannane as allylating agent. A variety of ketone substrates, including acetophenone derivatives and alpha,beta-unsaturated cyclic enones, reacted to form tertiary homoallylic alcohols in good yields (67-99%) and with high levels of enantioselectivity (generally >80%). A novel one-pot enantioselective allylation/diastereoselective epoxidation has also been introduced. Thus, upon completion of the allyl addition to conjugated cyclic enones, 1 equiv of tert-butyl hydroperoxide is added and the directed epoxidation of the allylic double bond ensues to afford the epoxy alcohol with high diastereoselectivity.

Catalytic Asymmetric Allylation of Ketones and a Tandem Asymmetric Allylation/Diastereoselective Epoxidation of Cyclic Enones

A simple, reliable, catalytic asymmetric allylation of ketones.

Solid State Structures and Solution Behavior of Titanium(IV) Octahydrobinaphtholate Complexes. Examination of Nonlinear Behavior in the Asymmetric Addition of Ethyl Groups to Benzaldehyde

Karen M. Waltz

Papers

Catalytic Asymmetric Allylation of Ketones and a Tandem Asymmetric Allylation/Diastereoselective Epoxidation of Cyclic Enones

A simple, reliable, catalytic asymmetric allylation of ketones.

Solid State Structures and Solution Behavior of Titanium(IV) Octahydrobinaphtholate Complexes. Examination of Nonlinear Behavior in the Asymmetric Addition of Ethyl Groups to Benzaldehyde

Atropisomeric amides: Achiral ligands with chiral conformations.

Catalytic Asymmetric Allylation of Ketones and a Tandem Asymmetric Allylation/Diastereoselective Epoxidation of Cyclic Enones.