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Published on: June 21, 2017
Efficient organocatalytic cross-aldol reaction between aliphatic aldehydes through their functional differentiation
Taichi Kano1, Hisashi Sugimoto, Keiji Maruoka
1Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
Journal of the American Chemical Society
|October 18, 2011
Summary
A new asymmetric direct cross-aldol reaction enables precise control over stereochemistry in synthesizing complex molecules. This method efficiently creates specific anti- or syn-aldol adducts using chiral catalysts.
Area of Science:
- Organic Chemistry
- Asymmetric Synthesis
- Catalysis
Background:
- The aldol reaction is a fundamental carbon-carbon bond-forming reaction in organic synthesis.
- Achieving high levels of chemo-, stereo-, and diastereoselectivity in cross-aldol reactions remains a significant challenge.
- Direct asymmetric cross-aldol reactions offer a more efficient route to complex aldol adducts compared to traditional methods.
Purpose of the Study:
- To develop a chemo- and stereoselective asymmetric direct cross-aldol reaction.
- To achieve enantio- and diastereocontrol in the formation of cross-aldol adducts between aliphatic aldehydes and α-chloroaldehydes.
- To demonstrate the ability to selectively obtain either anti- or syn-aldol adducts.
Main Methods:
- Employing proline as an organocatalyst.
- Utilizing a novel axially chiral amino sulfonamide as a catalyst.
- Investigating the reaction between aliphatic aldehydes and α-chloroaldehydes.
Main Results:
- The developed method exclusively forms the cross-aldol adduct.
- High levels of enantioselectivity and diastereoselectivity were achieved.
- Both anti- and syn-aldol adducts were obtained with good to excellent stereoselectivities by judicious choice of catalyst.
Conclusions:
- A versatile and highly selective asymmetric direct cross-aldol reaction has been established.
- The use of proline or a novel chiral amino sulfonamide catalyst allows for controlled synthesis of specific aldol adducts.
- This methodology provides a powerful tool for the stereoselective synthesis of valuable organic compounds.
Related Concept Videos
01:04Crossed Aldol Reactions: Overview
Crossed aldol addition is the reaction between two different carbonyl compounds under acidic or basic conditions. Here, both the carbonyl compounds function as nucleophiles and electrophiles. As shown in Figure 1, such a reaction yields a mixture of products, two of which are formed via self-condensation, while the remaining two are formed via crossed-condensation. Without adjustment, the reaction's usefulness in organic chemistry is decreased.
00:56Crossed Aldol Reaction Using Strong Bases: Directed Aldol Reaction
The reaction between two different carbonyl compounds comprising α hydrogen in the presence of a strong base like lithium diisopropylamide (LDA) to form a crossed aldol product is known as a directed aldol reaction. The directed aldol reaction is depicted in Figure 1.
01:10C–C Bond Formation: Aldol Condensation Overview
Aldol condensation is an important route in synthetic organic chemistry used to generate a new carbon–carbon bond under basic or acidic conditions. The aldol condensation reaction presented in Figure 1 constitutes an aldol addition reaction followed by the dehydration process.
01:14Crossed Aldol Reaction Using Weak Bases
This lesson deals with the crossed aldol reaction using weak bases. The self-condensation of an aldehyde having α hydrogen is prevented by adding it slowly to a mixture of formaldehyde and weak bases like hydroxide and alkoxide. Upon slow addition of the aldehyde, the base deprotonates the α carbon of the aldehyde to form the corresponding enolate. The enolate subsequently attacks the formaldehyde to form a single crossed product. Figure 1 depicts the aforementioned reaction.
01:08Base-Catalyzed Aldol Addition Reaction
As depicted in Figure 1, base-catalyzed aldol addition involves adding two carbonyl compounds in aqueous sodium hydroxide to form a β-hydroxy carbonyl compound.
01:15Acid-Catalyzed Aldol Addition Reaction
The aldol reaction of a ketone under acidic conditions successfully forms an unsaturated carbonyl as the final product instead of an aldol. The acid-catalyzed aldol reaction is depicted in Figure 1.