Intermolecular cycloaddition of N-boranonitrone with alkenes
Nobuyoshi Morita1, Kenji Fukui, Jinshi Irikuchi
1Showa Pharmaceutical University, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan.
The Journal of Organic Chemistry
|August 30, 2008
Summary
A novel N-boranonitrone cycloaddition reaction efficiently synthesizes isoxazolidines. This method provides a valuable route to 1,3-anti aminoalcohol derivatives, crucial building blocks in organic synthesis.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Medicinal Chemistry
Background:
- The synthesis of complex organic molecules often relies on efficient cycloaddition reactions.
- Isoxazolidines are important heterocyclic compounds with diverse applications in pharmaceuticals and organic synthesis.
- Developing new synthetic methodologies for isoxazolidine construction is an active area of research.
Purpose of the Study:
- To develop a novel synthetic route to isoxazolidines using N-boranonitrone intermediates.
- To investigate the stereochemical outcomes of intermolecular cycloaddition reactions with various alkenes.
- To explore the utility of the synthesized isoxazolidines for the preparation of valuable aminoalcohol derivatives.
Main Methods:
- Generation of N-boranonitrone E from ethyl glyoxylate O-tert-butyldimethylsilyloxime using BF3 x OEt2.
- Intermolecular [3+2] cycloaddition of N-boranonitrone E with a range of alkenes.
- Analysis of reaction products, including stereochemical determination of isoxazolidines.
- Reductive cleavage of the N-O bond in isoxazolidines to yield aminoalcohols.
Main Results:
- The N-boranonitrone cycloaddition reaction afforded isoxazolidines in moderate to high yields.
- Concerted cycloaddition predominantly yielded 3,5-trans isoxazolidines with most alkenes.
- 1-Methylated cyclic alkenes unexpectedly produced 3,3a-cis-cycloadducts, suggesting a stepwise mechanism.
- Terminal alkenes yielded products amenable to conversion into 1,3-anti aminoalcohol derivatives.
Conclusions:
- A new and efficient method for synthesizing isoxazolidines via N-boranonitrone cycloaddition has been established.
- The reaction exhibits tunable stereoselectivity based on the alkene substrate, with a mechanistic shift observed for methylated cyclic alkenes.
- This methodology offers a practical pathway for accessing valuable 1,3-anti aminoalcohol derivatives, expanding synthetic capabilities in organic chemistry.
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One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
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02:46Halogenation of Alkenes
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02:15Preparation of Alcohols via Addition Reactions
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The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation...
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02:38Electrophilic Addition to Alkynes: Halogenation
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