Related Experiment Video
Updated: Jul 12, 2026
10:17
Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Synthesis, resolution, and absolute stereochemistry of (1R, 2S)-(+)-cis-1-methoxycarbonyl-2-methylcyclobutane
The Journal of Organic Chemistry
|October 14, 2000
Summary
Efficient synthesis of cis-1-methoxycarbonyl-2-methylcyclobutane was achieved. Subsequent separation of amides led to a revised absolute stereochemistry determination via X-ray crystallography for this cyclobutane derivative.
Area of Science:
- Organic Chemistry
- Stereochemistry
- Crystallography
Background:
- Accurate determination of stereochemistry is crucial in organic synthesis.
- Cyclobutane derivatives present unique synthetic challenges.
- Chiral auxiliaries are often employed for stereochemical resolution.
Purpose of the Study:
- To efficiently synthesize a stereochemically pure cis-1-methoxycarbonyl-2-methylcyclobutane.
- To resolve the racemic mixture into its enantiomers using chiral amides.
- To revise the absolute stereochemistry of the cyclobutane derivative.
Main Methods:
- Multi-step synthesis of racemic cis-1-methoxycarbonyl-2-methylcyclobutane.
- Formation and separation of diastereomeric amides using (R)-(-)-phenylglycinol.
- X-ray crystallographic structure determination of a resolved amide.
Main Results:
- Efficient five-step synthesis of the target cyclobutane ester.
- Successful separation of the diastereomeric amides.
- X-ray crystallography revealed the absolute stereochemistry as (1R,2S), revising previous assignments.
Conclusions:
- A robust synthetic route to enantiomerically enriched cis-1-methoxycarbonyl-2-methylcyclobutane was established.
- The study successfully revised the absolute stereochemistry of the cyclobutane derivative.
- This work highlights the importance of crystallographic confirmation in stereochemical assignments.
Related Concept Videos
02:30Stability of Substituted Cyclohexanes
This lesson discusses the stability of substituted cyclohexanes with a focus on energies of various conformers and the effect of 1,3-diaxial interactions.
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...
02:37Disubstituted Cyclohexanes: cis-trans Isomerism
Depending upon the different spatial orientation of the substituents, the disubstituted cycloalkanes exhibit two types of stereoisomers. The cis isomers have the substituents on the same side of the ring, whereas the trans isomers have the substituents on the opposite sides. These stereoisomers exhibit different physical properties and cannot be interconverted without breaking the carbon-carbon bonds.
In cyclohexane, the substituents can occupy different positions generating distinct isomers.
In cyclohexane, the substituents can occupy different positions generating distinct isomers.
02:32Stereoisomers
On the basis of mirror symmetry, stereoisomers of an organic molecule can be further classified into diastereomers and enantiomers. Diastereomers are stereoisomers that are not mirror images of each other. Substituted alkenes, such as the cis and trans isomers of 2-butene, are diastereomers, as these molecules exhibit different spatial orientations of their constituent atoms, are not mirror images of each other, and do not interconvert. Here, the interconversion is suppressed due to restricted...
02:33Stereoisomerism of Cyclic Compounds
In this lesson, we delve into the role of ring conformation and its stability, which determines the spatial arrangement and, consequently, the molecular symmetry and stereoisomerism of cyclic compounds. 1,2-Dimethylcyclohexane is used as a case study to evaluate the possible number of stereoisomers. Here, given the multiple (n = 2) chiral centers, there are 2n = 4 possible configurations that lack a plane of symmetry, as the ring skeleton exists in a non-planar chair conformation. In addition,...
02:05Prochirality
The concept of prochirality leads to the nomenclature of the individual faces of a molecule and plays a crucial role in the enantioselective reaction. It is a concept where two or more achiral molecules react to produce chiral products. A typical process is the reaction of an achiral ketone to generate a chiral alcohol. Here, the achiral reactant reacts with an achiral reducing agent, sodium borohydride, to generate an equimolar mixture of the chiral enantiomers of the product. For example, an...
01:28Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
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.