Efficient Large-Scale Radical Deoxygenation in Alcoholic Solvents Using Sodium Hypophosphite and a Phase-Transfer Agent:  Application to Erythromycins

Graham, Alexandra E.; Thomas, and Albert V.; Yang, Rachel

doi:10.1021/jo991645o

Cited by 30 publications

(5 citation statements)

References 10 publications

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“…An immediate problem with NaH 2 PO 2 is its insolubility in most organic solvents. A recent report from the Abbott Laboratories addressed this problem, by describing the use of a phase-transfer agent in alcoholic solvents for the large scale deoxygenation of an erythromycin derivative, and demonstrated the usefulness of NaH 2 PO 2 in radical reductions . However, investigations aimed at the preparation of organophosphorus compounds from hypophosphites under radical conditions have apparently not been conducted since Nifant'ev's studies.…”

Section: Resultsmentioning

confidence: 99%

Triethylborane-Initiated Room Temperature Radical Addition of Hypophosphites to Olefins: Synthesis of Monosubstituted Phosphinic Acids and Esters

2001

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A novel and practical approach to monosubstituted phosphinic acid (alkylphosphonous acid) derivatives from hypophosphite salts or esters is described. Phosphorus-centered radical formation is initiated with Et(3)B/O(2), and the reaction is conveniently conducted at room temperature in an open flask. In contrast to previously reported conditions for the radical reaction of hypophosphorous acid and sodium hypophosphite (peroxide initiators, acid catalysis, heat), the method proceeds under neutral conditions and therefore tolerates a wide range of functional groups. Previously inaccessible phosphinic acids can be prepared in a single step from cheap starting materials. Excellent selectivity is observed for monoaddition, and symmetrical dialkyl phosphinates do not form in significant amounts. Monosubstituted phosphinic acids are usually obtained in better than 90% purity by a simple extractive workup; however, isolated yields are diminished if the substituent is polar. Because radicals derived from hypophosphites are electrophilic, the reaction is limited to the use of electron-rich olefins. The reaction conditions can also be employed in the room temperature radical reduction of alkyl halides and provide an exceptionally mild and environmentally friendly alternative to the use of tributyltin hydride. The remarkable mild nature of the reaction conditions allows for the radical reaction of sensitive alkyl hypophosphites to occur, in which case, a catalytic amount of Et(3)B suffices to deliver alkyl phosphinate esters in reasonable yield.

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Section: Resultsmentioning

confidence: 99%

Triethylborane-Initiated Room Temperature Radical Addition of Hypophosphites to Olefins: Synthesis of Monosubstituted Phosphinic Acids and Esters

2001

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“…108 A similar deoxygenation has also been conducted in alcoholic solvents using NaH 2 PO 2 as the reagent and a water soluble AIBN analogue as initiator (large scale, up to 15 g). 109 The Murphy first showed that hypophosphorous acid salts can also be used as reducing reagents in radical C-C-bond forming reactions. 111 For example, allyl ether 58 was cyclized to benzofuran derivative 59 (Scheme 20).…”

Section: Scheme 18mentioning

confidence: 99%

Tin Hydride Substitutes in Reductive Radical Chain Reactions

Studer¹,

Amrein²

2002

Synthesis

233

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The substitution of a functional group for a hydrogen atom is a very important transformation in synthetic organic chemistry. Reactions such as deoxygenations, deselenations, deaminations, dehalogenations, and decarboxylations fall into this category. Such reactions can be conducted efficiently using free radical chemistry. These defunctionalizations can be combined with C-C-bond forming processes. Radical reactions are generally conducted under very mild conditions. Various sensitive functional groups are tolerated under free radical conditions. Tin hydrides (Bu 3 SnH, Ph 3 SnH, Me 3 SnH) have been successfully employed in radical chemistry over the last 40 years, however there are drawbacks associated with tin-based chemistry. Organotin compounds are toxic and very often problems occur with product purification. Therefore, various attempts have been made to overcome these problems. In the present review article, we summarize the achievements on the development of tin hydride substitutes in reductive radical chain reactions.

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“…We started our studies with the radical reduction of p -bromobenzyl bromide, using 2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (VA-044) as the radical initiator and sodium hypophosphite monohydrate as the hydrogen atom donor (Scheme a). − We thought that using a low-temperature water-soluble initiator and a water-soluble hydrogen atom donor would allow the ability to develop isolation conditions where we could isolate our potential products via a water wash. Upon milling for extended periods of time at 45 °C in the presence of our water-soluble initiator, we observed only unreacted starting materials.…”

Section: Resultsmentioning

confidence: 99%

Radical Reduction of Alkyl and Aryl Halides under Mechanochemical Conditions

Silva,

Hellmann,

Mack

2023

ACS Sustainable Chem. Eng.

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Herein, we report a novel method for solvent-free reduction of alkyl and aryl halides under mechanochemical conditions. Reduction reactions were performed by using various alkyl and aryl halides in the presence of different radical initiators and hydrogen atom donors at elevated temperatures. Although we think the mechanism for the reaction under mechanochemical conditions is similar to that observed in solution, we observed a few differences. We found that tris(trimethylsilyl)silane-mediated reductions using AIBN as an initiator gave the highest yields. To the best of our knowledge, this reports the first use of mechanochemistry as a benign tool to perform reduction reactions of alkyl and aryl halides.

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Efficient Large-Scale Radical Deoxygenation in Alcoholic Solvents Using Sodium Hypophosphite and a Phase-Transfer Agent: Application to Erythromycins

Cited by 30 publications

References 10 publications

Triethylborane-Initiated Room Temperature Radical Addition of Hypophosphites to Olefins: Synthesis of Monosubstituted Phosphinic Acids and Esters

Triethylborane-Initiated Room Temperature Radical Addition of Hypophosphites to Olefins: Synthesis of Monosubstituted Phosphinic Acids and Esters

Tin Hydride Substitutes in Reductive Radical Chain Reactions

Radical Reduction of Alkyl and Aryl Halides under Mechanochemical Conditions

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