Triphosgene–pyridine mediated stereoselective chlorination of acyclic aliphatic 1,3-diols

Villalpando, Andres; Saputra, Mirza A.; Tugwell, Thomas H.; Kartika, Rendy

doi:10.1039/c5cc06365e

Cited by 12 publications

(2 citation statements)

References 29 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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“…Deoxychlorination proved challenging in the face of facile competing elimination processes that generated conjugated dienes. Kartika’s conditions were uniquely effective, and provided chloride 12 with minimal loss of enantiopurity …”

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confidence: 99%

A Chlorine-Atom-Controlled Terminal-Epoxide-Initiated Bicyclization Cascade Enables a Synthesis of the Potent Cytotoxins Haterumaimides J and K

et al. 2019

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Haterumaimide J (hatJ) is reportedly the most cytotoxic member of the lissoclimide family of labdane diterpenoids. The unusual functional group arrangement of hatJ-C18 oxygenation and C2 chlorination-resisted our efforts at synthesis until we adopted an approach based on rarely studied terminal epoxide-based cation-π bicyclizations that is described herein. Using the C2chlorine atom as a key stereocontrol element and a furan as a nucleophilic terminator, the key structural features of hatJ were rapidly constructed. The 18-step stereoselective synthesis features applications of chiral pool starting materials, and catalyst-, substrate-, and auxiliary-based stereocontrol. Access to hatJ and its acetylated congener hatK permitted their biological evaluation against aggressive human cancer cell lines. Our laboratory has been investigating the chemistry and biology of the potently cytotoxic labdane diterpenoids in the lissoclimide family. 1-3 Nearly two dozen such natural products were isolated from sea squirts as described by the groups of Malochet-Grivois/Roussakis, 4 Ueda/Uemura, 5 and Schmitz. 6 Among these compounds, many of which were named haterumaimides, several showed potent cytotoxicity against the P388 murine leukemia cell line (Figure 1); dichlorolissoclimide (1) and chlorolissoclimide (2) were also very active against KB cells and non-small-cell lung cancer, 4b,c and were later shown by Pelletier and co-workers to be inhibitors of eukaryotic translation. 7 With the Alexanian group, we completed semisyntheses of haterumaimide Q (3) and chlorolissoclimide from sclareolide, featuring in the latter case a selective radical C-H chlorination reaction to install the salient C2-halogen atom. 1,8 In a separate report focused more on the biological properties of these *

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Applications of Pictet–Spengler reaction in the total synthesis of alkaloids

Heravi

Zadsirjan

2021

Recent Applications of Selected Name Reactions in the Total Synthesis of Alkaloids

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Triphosgene–pyridine mediated stereoselective chlorination of acyclic aliphatic 1,3-diols

Cited by 12 publications

References 29 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

A Chlorine-Atom-Controlled Terminal-Epoxide-Initiated Bicyclization Cascade Enables a Synthesis of the Potent Cytotoxins Haterumaimides J and K

Applications of Pictet–Spengler reaction in the total synthesis of alkaloids

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