Propargylic acetals reduction

The unsaturated c.vo-enol lactone 17 is obtained by the coupling of propargylic acetate with 4-pentynoic acid in the presence of KBr using tri(2-furyl)-phosphine (TFP) as a ligand. The reaction is explained by the oxypalladation of the triple bond of 4-pentynoic acid with the ailenyipailadium and the carbox-ylate as shown by 16, followed by reductive elimination to afford the lactone 17. The ( -alkene bond is formed because the oxypalladation is tnins addition[8]. 

Scheme 2.14 Synthesis of allenes 38 and 40 by reduction of propargyl acetates with lithium dimethylcuprate. THP = tetrahydropyranyl.

Scheme 2.15 Reduction of propargyl acetates to terminal allenes with Stryker s reagent.

Scheme 2.58 Palladium-catalyzed reduction of propargylic acetates with samarium diiodide.

Palladium-catalyzed reduction of propargyl acetates is possible with Sml2 in the presence of a proton source (Scheme 3.17) [51]. The allene/alkyne selectivity is greatly influenced by the choice of the proton source. Propargyl phosphates were also converted into hydridoallenes by Pd-catalyzed reduction with Sml2 [52],... 

Reduction of propargylic compounds with Sml2 is possible in the presence of Pd catalysts. Propargylic acetates 233 are converted mainly to the allene 236 by Pd-catalysed reaction with Sml2 in the presence of a proton source [51]. In this reaction, the allenylpalladium 234 is reduced with Sm(II) to the allenyl anion 235, which is protonated to give allene 236. The alkyne 237 is a byproduct. 2,3-Naphthoquinodi-methane (240) as a reactive intermediate, can be generated by applying this reaction. 

Reduction of alkynes to cis-alkenes.1 This relatively stable copper hydride (1) reduces terminal alkynes at 25° internal alkynes are reduced at 80° to cis-alkenes exclusively. These reductions require 2 hydride equivalents of the complex, and 5-10 equiv. of H20 is necessary for satisfactory yields. Under these conditions, a tertiary propargyl acetate was converted to an allene (equation I). 

Another, albeit less-frequently employed option for a copper-mediated reduction of propargylic electrophiles to allenes relies upon the use of a copper hydride, for example, Stryker s reagent [(Ph3P)CuH]6. This reagent was applied by Brummond and Lu147 to the synthesis of the structurally complex precursor 197 for a potent antitumor agent, ( )-hydroxymethylacylfulvalene, from propargyl acetate 196 (Equation (11)). 

The most popular methods of preparing optically active l-octyn-3-ol involve asymmetric reduction of l-octyn-3-one with optlcally-active alcohol complexes of lithium aluminum hydride or aluminum hydride. These methods give optical purities and chemical yields similar to the method reported above. A disadvantage of these metal-hydride methods is that some require exotic chiral alcohols that are not readily available in both enantiomeric forms. Other methods include optical resolution of the racemic propargyl alcohol (100 ee) (and Note 11) and microbial asymmetric hydrolysis of the propargyl acetates (-15% ee for l-heptyn-3-ol)... 

Reduction of Cp2TiCl2 with Mg in the presence of propargyl acetates gives allenyl Ti intermediates which react with nucleophilic reagents such as aldehydes, ketones, acetonitrile, and allyl bromide to give carbon-carbon bondforming products in moderate yields.1149... 

Propargyl acetates undergo reductive isomerization to give terminal allenes. Conjugate additions. Interesting preparations pertain to the synthesis of 3-tri-fluoromethyl-3-hydroxyalkanoic acids, 3-aminomethylcycloalkanones, and 4-vinyl-2-acetoxy-2-cyclobutenones. Compounds of the last type give catechol derivatives on thermolysis. 

The Pd(II) species on an allenylpalladium complex A has ample Lewis acidity to activate a triple bond, on which a suitably arranged carboxylate anion attacks intramolecularly. Reductive elimination of Pd(0) species completes the formation of exo-enol lactones (Scheme The Pd-catalyzed coupling of the propargylic acetates with 4-pentynoic acids proceeds very smoothly in the presence of potassium bromide using tris(2-furyOphosphine (TFP) as the ligand (Scheme 10). 

Similar to alkynes, allenes can be converted to alkenes without over-reduction of the olefin. Thus, good yield of terminal olefin 18 was obtained from aUene 17 (Scheme 8). Allene 20 could in turn be prepared from propargyl cabonate 19 under slightly modified reaction conditions. For comparison, reactions using the corresponding propargyl acetates were much less satisfactory (Scheme 9). 

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