Diastereoselective Synthesis of cis-2,6-Disubstituted Dihydropyrane Derivatives through a Competitive Silyl-Prins Cyclization versus Alternative Reaction Pathways
Abstract
:1. Introduction
- (a)
- Selective methodologies are needed to obtain exclusively allyl- or vinyl silylalcohols from a common allylsilane precursor (conditions A and B, Scheme 1).
- (b)
- Alternative reaction pathways may interfere in the silyl-Prins cyclization reaction outcome [19], generating complex mixtures due to the formation of highly reactive intermediates.
2. Results
2.1. Synthesis of Allyl- and Vinylsilyl Alcohols
2.2. Study of the Silyl-Prins Cyclization with Allylsilyl Alcohols 2
2.3. Silyl-Prins Cyclization Study of Vinylsilyl Alcohols 3
2.4. Reaction Mechanism Study
3. Materials and Methods
3.1. General Remarks
3.2. Synthesis of Allyl(diphenyl)silane 1
3.3. Synthesis of Allylsilyl Alcohols 2
3.4. Synthesis of Vinylsilyl Alcohols 3
3.5. TMSOTf-Promoted Cyclization Reaction to Afford Dihydropyranes 4
3.6. BF3·OEt2-Promoted Diels Alder Reaction to Afford Derivatives 5
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Entry | R1 | R2 | R3 | LA (1 equiv.) | T (°C) | NMR Analysis (Isolated Yield) |
---|---|---|---|---|---|---|
1 | CH3 | CH2CH2Ph | H | TMSOTf | −78 | 3 |
2 | CH3 | CH2CH2Ph | H | TMSOTf | 0 | Complex mixture |
3 a | CH3 | CH2CH2Ph | H | TMSOTf | −78 | Complex mixture |
4 | CH3 | CH2CH2Ph | H | BF3·OEt2 | −78 | Complex mixture |
5 | CH3 | CH=CHPh | H | TMSOTf | −20 | Aldehyde |
6 a | CH2Ph | CH3 | H | TMSOTf | −78 | 3a + 4a |
7 a | CH2Ph | CH2Ph | H | TMSOTf | −78 | 4i |
8 a | Ph | CH3 | H | TMSOTf | −78 | Complex mixture |
9 | Ph | CH2CH2Ph | H | TMSOTf | −78 | Complex mixture |
10 | CH3 | CH=CHPh | TMS | TMSOTf | −78 | 2a |
11 | CH3 | CH=CHPh | TMS | BF3·OEt2 | −78 | Complex mixture |
12 | CH3 | CH=CHPh | TMS | BF3·OEt2 | 0 | 5 (29%) |
Entry | LA (equiv.) | Temperature (°C) | Isolated Yield |
---|---|---|---|
1 a | BF3·OEt2 (1.0) | 0 | Complex mixture |
2 | BF3·OEt2 (1.2) | 0 | Complex mixture |
3 | BF3·OEt2 (0.5) | 0 | Complex mixture |
4 | TMSCl (1.5) | 0 to rt b | nr |
5 a | TMSOTf (1.0) | −78 | 35% |
6 | TMSOTf (1.0) | −78 | 48% |
7 | TMSOTf (0.5) | −78 | 25% |
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Peña, L.F.; López, E.; Sánchez-González, Á.; Barbero, A. Diastereoselective Synthesis of cis-2,6-Disubstituted Dihydropyrane Derivatives through a Competitive Silyl-Prins Cyclization versus Alternative Reaction Pathways. Molecules 2023, 28, 3080. https://doi.org/10.3390/molecules28073080
Peña LF, López E, Sánchez-González Á, Barbero A. Diastereoselective Synthesis of cis-2,6-Disubstituted Dihydropyrane Derivatives through a Competitive Silyl-Prins Cyclization versus Alternative Reaction Pathways. Molecules. 2023; 28(7):3080. https://doi.org/10.3390/molecules28073080
Chicago/Turabian StylePeña, Laura F., Enol López, Ángel Sánchez-González, and Asunción Barbero. 2023. "Diastereoselective Synthesis of cis-2,6-Disubstituted Dihydropyrane Derivatives through a Competitive Silyl-Prins Cyclization versus Alternative Reaction Pathways" Molecules 28, no. 7: 3080. https://doi.org/10.3390/molecules28073080