Triphosgene–Amine Base Promoted Chlorination of Unactivated Aliphatic Alcohols

Villalpando, Andres; Ayala, Caitlan E.; Watson, Christopher B.; Kartika, Rendy

doi:10.1021/jo400341n

Cited by 28 publications

(3 citation statements)

References 32 publications

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“…This may be reasoned by the slightly acidic reaction medium. With triphosgene and pyridine tertiary chlorides are not amenable due to rivalling olefin formation [21c,d] …”

Section: Resultsmentioning

confidence: 99%

Lewis Base Catalysis Enables the Activation of Alcohols by means of Chloroformates as Phosgene Substitutes

2020

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Nucleophilic substitutions (S N) are typically promoted by acid chlorides as sacrificial reagents to improve the thermodynamic driving force and lower kinetic barriers. However, the cheapest acid chloride phosgene (COCl 2) is a highly toxic gas. Against this background, phenyl chloroformate (PCF) was discovered as inherently safer phosgene substitute for the S N-type formation of CÀ Cl and CÀ Br bonds using alcohols. Thereby, application of the Lewis bases 1-formylpyrroldine (FPyr) and diethylcyclopropenone (DEC) as catalysts turned out to be pivotal to shift the chemoselectivity in favor of halo alkane generation. Primary, secondary and tertiary, benzylic, allylic and aliphatic alcohols are appropriate starting materials. A variety of functional groups are tolerated, which includes even acid labile moieties such as tert-butyl esters and acetals. Since the by-product phenol can be isolated, a recycling to PCF with inexpensive phosgene would be feasible on a technical scale. Eventually, a thorough competitive study demonstrated that PCF is indeed superior to phosgene and other substitutes.

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“…This may be reasoned by the slightly acidic reaction medium. With triphosgene and pyridine tertiary chlorides are not amenable due to rivalling olefin formation [21c,d] …”

Section: Resultsmentioning

confidence: 99%

Lewis Base Catalysis Enables the Activation of Alcohols by means of Chloroformates as Phosgene Substitutes

2020

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“…R f (SiO 2 , cyclohexane) = 0.51; 1 H NMR (300 MHz, CDCl 3 , 25 °C): δ = 3.14 (t, J = 7.5 Hz, 2H), 3.79 (t, J = 7.5 Hz, 2H), 7.29−7.44 (m, 5H) ppm; 13 1-Chloro-2,2-diphenylethane (2d). 44 According to GP2, 2,2diphenylethanol (1d, 198 mg, 1.00 mmol), benzotrichloride (977 mg, 5.00 mmol), phenylsilane (108 mg, 1.00 mmol), and tri-noctylphosphane (37 mg, 0.10 mmol) were reacted and after purification by column chromatography (SiO 2 , cyclohexane), 2d (182 mg, 0.840 mmol, 84%) was obtained as yellow oil. R f (SiO 2 , cyclohexane) = 0.34; 1-Chloro-2-(4-bromophenyl)ethane (2e).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Organocatalytic Chlorination of Alcohols by P(III)/P(V) Redox Cycling

2019

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A catalytic system for the chlorination of alcohols under Appel conditions was developed. Benzotrichloride is used as a cheap and readily available chlorinating agent in combination with trioctylphosphane as the catalyst and phenylsilane as the terminal reductant. The reaction has several advantages over other variants of the Appel reaction, e.g., no additional solvent is required and the phosphane reagent is used only in catalytic amounts. In total, 27 different primary, secondary, and tertiary alkyl chlorides were synthesized in yields up to 95%. Under optimized conditions, it was also possible to convert epoxides and an oxetane to the dichlorinated products.

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“…However, activation of the strong sp 3 hybridized C–O bond toward chloride ion attack is necessary and is achieved by conversion of alkyl alcohols, for instance, into the corresponding sulfonate esters . Chlorodehydration of alcohols by in situ activation of the C–O bond has been studied extensively (Scheme a), providing a range of transformations best exemplified by the Appel reaction. ,, Catalytic variants of the Appel reaction, and other innovative catalytic chlorodehydrations, have recently been reported . However, despite the progress made, limitations remain such as the formation of side products, narrow substrate scope, reactivity issues, and the use of multiple reagents.…”

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confidence: 99%

Desulfurative Chlorination of Alkyl Phenyl Sulfides

et al. 2017

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The chlorination of readily available secondary and tertiary alkyl phenyl sulfides using (dichloroiodo)benzene (PhICl) is reported. This mild and rapid nucleophilic chlorination is extended to sulfa-Michael derived sulfides, affording elimination-sensitive β-chloro carbonyl and nitro compounds in good yields. The chlorination of enantioenriched benzylic sulfides to the corresponding inverted chlorides proceeds with high stereospecificity, thus providing a formal entry into enantioenriched chloro-Michael adducts. A mechanism implying the formation of a dichloro-λ-sulfurane intermediate is proposed.

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Triphosgene–Amine Base Promoted Chlorination of Unactivated Aliphatic Alcohols

Cited by 28 publications

References 32 publications

Lewis Base Catalysis Enables the Activation of Alcohols by means of Chloroformates as Phosgene Substitutes

Lewis Base Catalysis Enables the Activation of Alcohols by means of Chloroformates as Phosgene Substitutes

Organocatalytic Chlorination of Alcohols by P(III)/P(V) Redox Cycling

Desulfurative Chlorination of Alkyl Phenyl Sulfides

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