A new method for the radical deoxygenation of tertiary alcohols

Barton, Derek H. R.; Crich, David

doi:10.1039/c39840000774

Cited by 36 publications

(8 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To explore methods for the preparation of the required selenium-containing ring systems (e.g., 1f ), we first turned our attention to the preparation of 2,2-dibutylselanane ( 7 ), a model compound. Barton, Crich, and co-workers reported some time ago a convenient way to generate radicals from tertiary alcohols by the use of PTOC oxalates (anhydrides of an oxalic acid monoester and N -hydroxypyridine-2-thione) . It was envisaged that free-radical homolytic substitution chemistry involving an appropriately substituted tertiary radical would produce the desired selenacycle.…”

Section: Resultsmentioning

confidence: 99%

Intramolecular Homolytic Substitution at Selenium: Synthesis of Novel Selenium-Containing Vitamin E Analogues

et al. 2001

View full text Add to dashboard Cite

Treatment of 1-(benzylselenenyl)-5-butyl-5-nonanol (10) with oxalyl chloride followed by the sodium salt of N-hydroxypyridine-2-thione afforded the corresponding pyridine-2-thione-N-oxycarbonyl (PTOC) oxalate ester which was not isolated but immediately heated to provide 2,2-dibutylselenane (7). This transformation presumably involves a tertiary alkyl radical that undergoes intramolecular homolytic substitution at selenium with loss of the benzyl radical to provide the selenium-containing ring system (7). A similar protocol, when applied to 1-(2-benzylselenenyl-5-methoxyphenyl)-3-methyl-3-heptanol (18) and 1-(2-benzylselenenyl-5-methoxyphenyl)-3,7,11,15-tetramethyl-3-hexadecanol (19), followed by deprotection, afforded the selenium-containing alpha-tocopherol analogues 4 and 1f, respectively, in moderate yields. To the best of our knowledge, these transformations represent the first examples of tertiary radicals involved in homolytic substitution chemistry at selenium.

show abstract

Section: Resultsmentioning

confidence: 99%

Intramolecular Homolytic Substitution at Selenium: Synthesis of Novel Selenium-Containing Vitamin E Analogues

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Addition of vinylcerium , to 11 gave the exo alcohol, which upon treatment with 9-BBN gave the corresponding 4-hydroxythiane . The six-membered ring is obtained, as the addition of thiyl radicals to olefins is reversible and the thiane results from formation of the more stable secondary radical. − Attempts to prepare the half oxalate chloride of 14 for subsequent radical deoxygenation , were unsuccessful as treatment with oxalyl chloride resulted in elimination to give 15 instead. The unsaturated thiane was reduced to the thiane 16 by hydrogenation, but a mixture of inseparable products were obtained.…”

Section: Resultsmentioning

confidence: 99%

Catalytic Asymmetric Epoxidation of Aldehydes. Optimization, Mechanism, and Discovery of Stereoelectronic Control Involving a Combination of Anomeric and Cieplak Effects in Sulfur Ylide Epoxidations with Chiral 1,3-Oxathianes

et al. 1998

View full text Add to dashboard Cite

A range of 1,3-oxathianes based on camphorsulfonic acid have been prepared and tested in the catalytic asymmetric epoxidation of carbonyl compounds. It was found that the 1,3-oxathiane derived from acetaldehyde 5b gave the highest yield and enantioselectivity in the epoxidation process. The enantioselectivity was independent of the solvent and metal catalyst used (although yields were dependent on both). The optimum conditions were applied to a range of aldehydes, and good enantioselectivities and diastereoselectivities were observed. The origin of the enantioselectivity was probed, and in particular the role of the oxygen of the 1,3-oxathiane was investigated. Thus, the sulfur and carbon analogues of the camphorsulfonic acid based 1,3-oxathiane (derived from formaldehyde) were prepared (i.e., 1,3-dithiane and thiane analogues). With this series of analogues the steric effects are minimized so that the electronic effects can be investigated. The series of compounds was reacted in the catalytic cycle with benzaldehyde and gave stilbene oxides with 44% ee (sulfur analogue), 41% ee (1,3-oxathiane), and 20% ee (carbon analogue). Thus, it was concluded that the oxygen of the 1,3-oxathiane exerted a significant electronic effect in controlling the face selectivity of the ylide reactions. This electronic effect was a result of combined anomeric (higher with the sulfur analogue, not present with the carbon analogue) and Cieplak effects. A strong anomeric effect was observed in the X-ray structures of one of the 1,3-oxathianes, and an even greater one was observed in the corresponding sulfoxide (this was used as an electronic analogue of the ylide). The face selectivity of the ylide was believed to be complete in reactions with 5b. The minor enantiomer resulted from reaction of the minor conformer of the ylide, reacting again with high face selectivity. This was proven by using a more substituted diazo compound, which was expected to give much less of the minor conformer. Indeed, reaction with mesityldiazomethane gave the corresponding epoxide in essentially enantiomerically pure form.

show abstract

“…Attempted xanthate formation also failed. Protocols for the radical deoxygenation of tertiary alcohols and hindered secondary alcohols are reported by Barton, which involve formation of mixed oxalates,21 thioformates22 and phenylselenocarbonates 23. These too were ineffective.…”

Section: Resultsmentioning

confidence: 99%

Concise Stereocontrolled Formal Synthesis of (±)-Quinine and Total Synthesis of (±)-7- Hydroxyquinine via Merged Morita−Baylis−Hillman−Tsuji−Trost Cyclization

Webber

Krische

2008

J. Org. Chem.

View full text Add to dashboard Cite

Concise stereoselective syntheses of (±)-quinine and (±)-7-hydroxyquinine are achieved using a catalytic enone cycloallylation that combines the nucleophilic features of the Morita-Baylis-Hillman reaction and the electrophilic features of the Tsuji-Trost reaction. Cyclization of enone-allyl carbonate 11 delivers the product of cycloallylation 13 in 68% yield. Diastereoselective conjugate reduction of the enone 13 (>20:1 dr) followed by exchange of N-protecting groups provides the saturated N-Boc-protected methyl ketone 19, which upon aldol dehydration provides quinoline containing enone 15, possessing all carbon atoms of quinine. Exposure of ketone 15 to L-selectride enables diastereoselective carbonyl reduction (>20:1 dr) to furnish the allylic alcohol 16. Stereoselective hydroxyl-directed epoxidation using an oxovanadium catalyst modified by Nhydroxy-N-Me-pivalamide delivers epoxide 17 (17:1 dr). Cyclization of the resulting amine-epoxide 17 provides (±)-7-hydroxyquinine in 13 steps and 11% overall yield from aminoacetaldehyde diethyl acetal. Notably, highly stereoselective formation of five contiguous stereocenters is achieved through a series of 1,2-asymmetric induction events. A formal synthesis of (±)-quinine is achieved upon deoxygenation of the N-Cbz-protected allylic acetate 22 to provide olefin 23, which previously has been converted to quinine. Thus, (±)-quinine is accessible in 16 steps and 4% overall yield from commercial aminoacetaldehyde diethyl acetal, making this route the most concise approach to quinine, to date.

show abstract

A new method for the radical deoxygenation of tertiary alcohols

Abstract: Tertiary alcohols can be deoxygenated in a radical chain reaction based on their mixed oxalate esters with N-hydroxy-2-thiopyridone, these esters being obtained directly from the alcohols and oxalyl chloride etc. or via their trimethylsilyl derivatives.

Cited by 36 publications

References 3 publications

Intramolecular Homolytic Substitution at Selenium: Synthesis of Novel Selenium-Containing Vitamin E Analogues

Intramolecular Homolytic Substitution at Selenium: Synthesis of Novel Selenium-Containing Vitamin E Analogues

Catalytic Asymmetric Epoxidation of Aldehydes. Optimization, Mechanism, and Discovery of Stereoelectronic Control Involving a Combination of Anomeric and Cieplak Effects in Sulfur Ylide Epoxidations with Chiral 1,3-Oxathianes

Concise Stereocontrolled Formal Synthesis of (±)-Quinine and Total Synthesis of (±)-7- Hydroxyquinine via Merged Morita−Baylis−Hillman−Tsuji−Trost Cyclization

Contact Info

Product

Resources

About