Enol tosylates

Replacement of carbonyl by sulphur is achieved via enol tosylate (4) and the rest is simply an adjustment... 

Evaluate use of the related enol tosylate- which should be accessible from cheaper and more readily available reagents... 

Enolizahon of cyanoketone rac-5 under the previously optimized conditions, followed by reaction with p-toluenesulfonic anhydride afforded a 90 10 ratio of the two expected enol tosylates in 90% yield. An immediate advantage of the tosylates compared to the triflate was seen on isolation, when the desired compound 32 was found to be a crystalline solid. In this way an 85% isolated yield of 32 as a single isomer could be achieved without the need for chromatography (Scheme 9.24). Use of p-toluenesulfonyl chloride in place of the anhydride led to a-chlorination... 

Use of the above conditions in conjunction with the enol tosylate 32, provided only low yields of 22, prompting an extensive screening of structurally diverse phosphine ligands/solvents and palladium sources to attempt to define suitable conditions. Quite quickly a number of conditions were found to be effective, with chelating diphosphines being superior to monodentate phosphines (Table 9.7). In... 

The reaction conditions were optimized to afford clean coupling of enol tosylate 32 using only a slight excess of amide 24 (1.05equiv) at 100 °C, 5mol% Pd2(dba)3/ dppb catalyst, and a toluene/tert-amyl alcohol solvent system. Even under the harsh reaction conditions required for complete conversion of the tosylate (100 °C, 20 h) no detectable E/Z isomerization was seen, providing further proof that the hindered nature of the enamide aids stability to isomerization. Treatment of the mixture with activated carbon (Darco KB-B) at the end of the reaction followed by isolation of the product by crystallization, afforded enamide 22 in 92% isolated yield. 

The use of the enol tosylate compared to the enol triflate for the above amidation offers the advantage of a cheaper reagent to prepare the substrate and generation of a crystalline intermediate. Based on these positive attributes the scope of this reaction was explored (Scheme 9.26) [25, 26]. 

Treatment of the enol tosylate obtained with amines led to the formation of / -amino-a-fluoro acrylaldehydes (Eq. 90) when bifunctional nitrogen nucleophiles were used, pyrazoles and pyrimidines were obtained [267]. More recently the reaction has been used to prepare the alkyl- or arylthio congeners [268]. 

For the use of enol tosylates of 1,2-diketoncs as substrates, see Charonnat Mitchell Keogh Tetrahedron Lett. 1990,3/, 315. 

One of the very rare cases where a triple bond is formed by a normal Grob fragmentation is described by Corey in the course of the synthesis of hybrida lactone (45), an eicosanoid, isolated fix)m the marine alga Laurencia hybrida. The strained enol tosylate (43) yields the ethynyl ketone (44) under very mild... 

Enantiomerically pure (+ )-64, available from the racemate by recrystallization of the diastereomeric bisulfite complexes with (-)-a-phenylethylamine, was converted to the (Z)-enol tosylate 65 (49%). This material was separated from the corresponding ( )-olefin (3%) and starting material 64 (19%) by chromatography. Condensation of 65 with optically active cw-2-ethylcyclopropyl lithium (66) afforded a single cyclobutanol 67 in 76% yield. Fragmentation to the desired rranj-disubstituted cyclopropane ring was induced by addition of tetrabutylammonium fluoride, which also served to equilibrate the initially formed cis compound to a mixture of 68b to 68a (9 1) in a combined yield of 86%. The less stable 68a could readily be equilibrated to the mixture (9 1) of 68a,b by treatment with carbonate in methanol. 

This reaction has been modified for preparing of-halogenated ketones via enol tosylate, enol ethers," and enol silyl ether. ... 

Enol tosylates from 1,2-ditosylates Yfith simultaneous formation of acoxy compds. from tosylates... 

Klapars reported the synthesis of enamides by the coupling of enol tosylates with amides [181], Here, an i-propyl-derivative of dppf was used as ligand together with the weak bases K3PO4 or K2CO3 in t-AmOH as solvent. Previously, XantPhos and CS2CO3 were used for the same purpose in 1,4-dioxane as solvent by Wallace [182],... 

Anion Chemistry. The fluorovinyl anion 3 (eq 1) is a versatile intermediate and can be reacted with a variety of electrophiles. When treated with ketones, the anion gives secondary alcohols which can be sequentially hydrolyzed, firstly to carboxy enol-tosylates under acidic conditions, and then under basic conditions to give synthetically useful a-keto carboxylic acids (eq 2). ... 

The above procedure does not work well with aliphatic carboxylic acids. In this case, aliphatic analogs of triflates from eq 4 are efficiently converted to l-(l-alkyn-l-yl)benzotriazoles by treatment with 10% NaOH (eq 6). In the following step, the aUcynyl derivatives are treated with p-toluenesulfonic acid monohydrate (in acetonitrile at 65 °C) to generate the corresponding enol tosylates, which are subsequently hydrolyzed with TBAF and 1 N HCl to furnish the desired acids (eq 7). The lowest yield (28%) is reported for R = PhCH2CH2, and all other yields fall into the range of 48-68%. ... 

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