Size-Programmable Matteson-Type Annulation: Construction of Spirocycles from Simple Cyclic Ketones
Woohyun Jo1, Juliane K Scholz1, Hairong Lyu1
1Department of Chemistry, University of Chicago, Chicago, IL, 60637, USA.
Angewandte Chemie (International Ed. in English)
|March 13, 2025
Summary
This study introduces an iterative boron-homologation method for synthesizing carbocycles and spirocycles. The novel approach enables diastereoselective and enantioselective ring formation from simple precursors.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Methodology Development
Background:
- Matteson-type reactions traditionally yield linear molecules.
- A need exists for efficient carbocycle and spirocycle synthesis.
Purpose of the Study:
- To develop a novel iterative boron-homologation strategy.
- To enable the construction of diverse carbocyclic and spirocyclic frameworks.
- To achieve diastereoselective and enantioselective ring formation.
Main Methods:
- Utilizing an electron-withdrawing group (EWG) as a handle for intramolecular Matteson-type couplings.
- Employing an iterative boron-homologation sequence.
- Investigating the role of Lewis acid additives.
Main Results:
- Successful synthesis of various carbocycles with different ring sizes and stereocenters.
- Demonstration of scalable annulation processes.
- Extension of the method to synthesize spirocyclic and double spirocyclic compounds from cyclic ketones.
Conclusions:
- The developed method provides a versatile route to complex carbocycles and spirocycles.
- The approach offers control over stereochemistry and is applicable to diverse substrates.
- This work expands the synthetic utility of Matteson-type reactions.
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
Related Concept Videos
01:27Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
2.1K
Robinson annulation is a base-catalyzed reaction for the synthesis of 2-cyclohexenone derivatives from 1,3-dicarbonyl donors (such as cyclic diketones, β-ketoesters, or β-diketones) and α,β-unsaturated carbonyl acceptors. Named after Sir Robert Robinson, who discovered it, this reaction yields a six-membered ring with three new C–C bonds (two σ bonds and one π bond).
2.1K
![[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2Ffiles%2Fmedia%2Fscience-education%2Fscience-education-thumbs%2F12417.jpg&w=3840&q=75)
01:16[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
9.9K
The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
9.9K
![[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2Ffiles%2Fmedia%2Fscience-education%2Fscience-education-thumbs%2F12422.jpg&w=3840&q=75)
01:21[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement
2.6K
The Cope rearrangement is classified as a [3,3] sigmatropic shift in 1,5-dienes, leading to a more stable, isomeric 1,5-diene. The reaction involves a concerted movement of six electrons, four from two π bonds and two from a σ bond, via an energetically favorable chair-like transition state.
2.6K
01:28Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
3.7K
The Diels–Alder reaction is one of the robust methods for synthesizing unsaturated six-membered rings. The reaction involves a concerted cyclic movement of six π electrons: four π electrons from the diene and two π electrons from the dienophile.
3.7K
01:01Ketones with Nonenolizable Aromatic Aldehydes: Claisen–Schmidt Condensation
3.6K
Benzaldehyde, like formaldehyde, lacks an α hydrogen and cannot enolize to form an enolate. Hence, the reaction of benzaldehyde with a ketone in the presence of an aqueous base forms a single crossed product. This reaction is referred to as Claisen–Schmidt condensation.
As the self-condensation of ketones is generally not favored in basic conditions, the self-condensed products do not form in the reaction between ketones and benzaldehyde. The general reaction of Claisen–Schmidt...
As the self-condensation of ketones is generally not favored in basic conditions, the self-condensed products do not form in the reaction between ketones and benzaldehyde. The general reaction of Claisen–Schmidt...
3.6K
01:16Cycloaddition Reactions: Overview
2.5K
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
2.5K