Yarovenko reagent

Several problems with Scheme 6 were identified. The Yarovenko reagent led to several percent of an impurity containing -CsCCH2C1, which proved difficult to remove, and the azide ring opening of the epoxide led to both possible hydroxyl azides. These problems and the need for a resolution step led to abandonment of Scheme 6. 

A C-11,12 double-bond rearranged product 24 was observed when 2, 7-deacetyl paclitaxel was treated with Yarovenko reagent (Et2NCF2CHFCl), which can be then transformed into 2 -Troc-10-deoxy paclitaxel (25) by catalytic hydrogenation, along with the formation of a small amount of 12-fluorinated 26. All taxoids, after deprotection, showed reduced cytotoxicity seven to eight times. 

The first reagent of this type, 2-chI()ro-A. .V-diethyl-l,l,2-trifIuoroclhylamine(l). was prepared by Pruett and co-workers in 1950. Yarovenko and Raksha utilized this reagent for the replacement of hydroxy groups by fluorine and, therefore, 1 is usually called the Yarovenko reagent". It is synthesized by the addition of diethylamine to chlorotrifluoroethene. ... 

If the substituent R is sterically hindered, the fluorination step is complicated and sometimes does not take place at all. For example, the hydroxy group of 5 cannot be substituted by fluorine with the Yarovenko reagent (1), instead the corresponding chlorofluoroacetate 6 is isolated as the sole product. ... 

Simple primary alcohols generally give high yields of the expected fluoro compounds when treated with the Yarovenko reagent, 2-chloro-Af,Af-diethyl-l,l,2-trifluorocthylamine (1). or the Ishikawa reagent, A, A-diethyl-l,l,2,3,3,3-hexafluoropropylamine (2) examples arc given in Tables 6 and 7. 

Tabic 6. Fluorinalion of Primary Alcohols with Yarovenko Reagents... 

In the aliphatic series there has been little work performed with fluoroalkylamine reagents (FAR). They do not seem to work well, since, for example, methyl 2-hydroxy-2-melhyl-propanoate and the Yarovenko reagent, 2-chloro-/V,/V-diethyl-l,1.2-trinuoroethylamine (1), give the desired methyl 2-fluoro-2-mclhylpropanoate in only 10% yield elimination is the main reaction. Good yields of fluorinated products are obtained from 2-aryl-2-hydroxy-acetates, where elimination cannot occur (sec Table 9). When alkyl substituents arc present in the a-position, elimination products arc again found. 

The fluorination of gibbcrellins - and kaurenoids with the Yarovenko reagent (1) has been investigated. Thus, the allylie 2/i-hydroxy group in esters of gibberellic acid reacts with... 

Fluorination of brefeldin A with an excess of the Yarovenko reagent (1) affords 4,7a-dilluoro-4,7-dideoxybrefeldin A (mp 86.5-88 C) in 12% yield. When substitution of the 10-hydroxy group of taxol was attempted with the Yarovenko reagent, an almost clean dehydration took place. No 10-fluoro compound was formed but a rearranged 12-nuorinated product was isolated as a byproduct in 13% yield. "... 

The early work in the steroid field was performed by Ayer14414- and Knox and co-workers.146147 Some of their work has been recently reinvestigated, i.e. the reaction of 3-hydroxy-5,6-unsaturated steroids with the Yarovenko reagent (1).14S In particular, 3/J-hydroxypregn-5-en-20-one (3) was reacted with the Yarovenko reagent in various solvents to give mixtures of the five isolated products 4-8.148... 

The fluoFoalkylamine reagent (FAR) 2-chloro-l,l,2-trifluorotriethylamine gives alkyl fluorides from alcohols in one step and is known as the Yarovenko reagent." This reagent is less reactive than DAST but was used intensively before the introduction of DAST. Rearrangement and elimination are similar with FAR and DAST (equations 39 and 40)." " This may be explained by the similar mechanism. Activation of the alcohol by intermediate formation of ester-type derivatives is followed by 5N2-type displacement by fluoride ion (Scheme 32). 

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