Asymmetric addition of alkenylmetals to aldehydes

Asymmetric addition of alkenylmetals to aldehydes

(a) Asymmetric addition of alkenylzinc to aldehyde in the total synthesis of muscone. (b) Detailed steps for the reaction. Structure of the ligand and the proposed transition state for the key addition reaction are shown..png

Asymmetric addition of alkenylmetals to aldehydes

The asymmetric addition of alkenylmetals to aldehydes is a significant reaction in organic chemistry that involves the addition of an alkenylmetal compound to an aldehyde to form a chiral allylic alcohol. This reaction is particularly important in the synthesis of complex natural products and pharmaceuticals due to its ability to create stereocenters with high enantioselectivity.

Mechanism

The reaction mechanism typically involves the coordination of the alkenylmetal to the carbonyl group of the aldehyde, followed by a nucleophilic addition to form the allylic alcohol. The choice of metal and the presence of chiral ligands are crucial for achieving high enantioselectivity. Common metals used in this reaction include zinc, titanium, and boron.

Chiral Ligands

Chiral ligands play a pivotal role in the asymmetric addition of alkenylmetals to aldehydes. These ligands create a chiral environment around the metal center, which influences the approach of the aldehyde and the alkenylmetal, leading to the formation of a chiral product. Examples of chiral ligands used in this reaction include BINAP, TADDOL, and chiral phosphine ligands.

Applications

The asymmetric addition of alkenylmetals to aldehydes is widely used in the synthesis of natural products and pharmaceuticals. For instance, this reaction has been employed in the synthesis of vitamin E, prostaglandins, and various antibiotics. The ability to form chiral centers with high enantioselectivity makes this reaction a valuable tool in asymmetric synthesis.

Examples

1. Synthesis of Vitamin E: The asymmetric addition of an alkenylzinc reagent to an aldehyde intermediate is a key step in the synthesis of vitamin E. 2. Prostaglandin Synthesis: The formation of chiral centers in prostaglandin synthesis often involves the asymmetric addition of alkenylmetals to aldehydes. 3. Antibiotic Synthesis: Several antibiotics with complex chiral structures are synthesized using this reaction to ensure the correct stereochemistry.

See Also

• Asymmetric synthesis
• Chiral ligand
• Enantioselectivity
• Allylic alcohol
• Organometallic chemistry