AUyl alcohols arylation

The impact of silver(l) and thaUium(I) salts [221] on Pd-catalyzed reactions extends beyond just increasing regioselectivities and enhancing reaction rates [202]. Without these additives, the arylation of aUyl alcohols 27 afforded aldehydes and ketones 30, rather than the fS-arylaUyl alcohols 33 (Scheme 8.7). Apparently, the P-hydride ehmination in the intermediate 28 is faster in the direction leading to enol 31. Alternatively, p-hydride ehmination to give the allyl alcohol 33 followed by readdition of the hydridopalladium species to the double bond and subsequent P-hydride ehmination to give the more stable enol 31 would explain the facts. This... 

Unfortunately, attempts to perform this substitution reaction on cyclohexenol and geraniol led to the exclusive formation of the corresponding silyl ethers. It thus would seem that one requirement for effective carbon-carbon bond formation is that allylic alcohols be secondary and have possess y,y-disubstitution. Pearson, however, discovered a method with less restriction on the natiue of the substrate he used allylic acetates with y-mono-substitution or primary alcohols [96]. Not only ketene silyl acetals but also a diverse set of nucleophiles including aUyl silane, indoles, MOM vinyl ether, trimethylsilyl azide, trimethylsilyl cyanide, and propargyl silane participate in the substitution of y-aryl allylic alcohol 90 to give allylated 91 (Sch. 45). Further experimental evidence suggests that these reactions proceed via ionization to allylic carboca-tions—alcohols 90 and 92 both afforded the identical product 93. 

The C-4 acids (183 and 184) have also been subjected to borane reduction conditions to afford alcohol 195 in 23-50% yield or 64% yield as the C-8 epimeric mixture (195 and 196, Scheme 29) [34, 49, 64]. The C-8 alcohol epimers 195 and 196 have been treated separately as a common intermediate for a number of C-4 derivatives including esters, ethers, and amines [34,49, 64]. Alcohols 195 and 196 was subjected to DCC, DMAP, and desired acid chloride or carboxylic acid in CH2CI2 affording ester analogs in 50-92% yield [64]. Esters prepared include alkyl, aryl, and fluorenylmethyloxycarbonyl (Fmoc) protected amino acid derivatives (197 and 198) [64]. Ethers were prepared with various alkyl halides and Ag20 in CH3CN at 40 °C. Alkyl, aUyl, and benzyl ethers were prepared in 45-80% yield (199 and 200) [34,64]. Alcohols 195 and 196 were then activated to the trifiates and displaced by a variety of amines by treatment with trifiuoromethanesulfonic anhydride and desired amine in 22% - quantitative yield over two steps (201 and 202)... 

AUylaniline, 22 Allyl aryl ethers, 2 AUylbromide, 111 AUyl ethyl ethers, 112 AUylic acetates, 120-121 Allylic alcohols, 116 AUylic amination, 316-317 Allylic chlorides, 225 Allylic hydroperoxidation, 26 3 AUyUc oxidation, 37-38... 

Danishefsky et al. developed a stereospedfic route for the synthesis of deoxy analog of mitomycin via an aromatic Claisen rearrangement [84]. The aUyl aryl ether 112 was prepared from allylic alcohols and phenol derivative via the Mitsu-nobu reaction. The aromatic Claisen rearrangement of 1,3-disubstituted aUyhc ether 112 proceeded under thermal conditions (N,N-dimethylaniline reflux) to afford the ortho rearrangement product 113 in 80% yield. 

Nucleophilic Displacement. PhTMS-BF3 0Et2 system has been shown to be useful in the transformation of allylic alcohols to allylic sulfides (eq IS). Preparation of unsymmetrical diaryl sulfides can be achieved by reaction of arenediazonium tetraflu-oroborates with PhSTMS (eq 19). In some cases, addition of cupric sulfide increases the yield of the diaryl sulfides. The use of (phenylthio)trimethylsilane as a coupling partner in palladium catalyzed reactions with aUyl carbonates (eq 20) and aryl iodide (eq 21) has been explored. ... 

---