Allylic alcohols Palladium-catalysed reaction

A procedure has been developed for the palladium-catalysed a-arylation of amides by aryl bromides using the zinc enolates of the amides. The reaction works well with bromoarenes carrying a variety of ring substituents and with bromopyridine. In addition, the reaction has been shown to be effective with morpholine amides to give products which are precursors for aldehydes and ketones.39 A new method has been reported for the allylation of aryl halides using homoallyl alcohols as the allyl source the palladium-catalysed reaction, which may be both stereo- and regio-sepecific, uses a retro-allylation reaction to form a a-allyl(aryl)palladium intermediate.40... 

The chemistry of allylic alcohols and their derivatives is remarkably rich. They can be used to add allyl groups to other molecules with good regio- and stereochemical control. The methods in this chapter, particularly the palladium-catalysed reactions and the sigmatropic rearrangements, should allow you to make many otherwise difficult target molecules. 

G-Allylic urethanes and carbonates are afforded from amines/alcohols, carbon dioxide and allylic chlorides by palladium catalysed reaction in the presence of an organobase. The choice of added base in the generation of carbamates/carbonates was critical for high yields... 

A combination of a Mizoroki-Heck reaction with an intramolecular aldol condensation is observed on treatment of aromatic aldehydes or ketones such as 184 with allylic alcohols 185 as described by Dyker and coworkers [102]. The palladium-catalysed reaction led to 187 via 186 in 55% yield (Scheme 8.48). 

The same group has successfully applied similar conditions to the Pd-cata-lysed asymmetric synthesis of allylic alcohols from unsymmetrical and symmetrical allylic carbonates and acetates, as shown in Scheme 2.57. Moreover, Trost et al. have demonstrated that the DYKAT palladium-catalysed reactions of conduritol B tetracarboxylates provided ready access to a variety of enan-tiomerically pure conduritol B derivatives. ... 

Bis(dibenzylideneacetonato)palladium in conjunction with l,2-bis(diphenyl-phosphino)ethane is a superior catalyst for the alkylation of lithium enolates with allylic acetates. Bis(pentan-2,4-dionato)palladium will catalyse the alkylation of pentan-2,4-dione by allylic alcohols, but the reaction is of limited value in its present form since the catalyst has been shown to cause rearrangements and disproportionation of allylic alcohols. ... 

The rate of the palladium-catalysed Heck-type phenylation of allylic alcohols has been found to be markedly enhanced by addition of tertiary amines454. Regioselectivity can be increased, in some cases, by adding E NCl or employing a Wilkinson Rh catalyst (rather than pd)455 456. Another Heck-type reaction involves addition of arenediazonium tetraflu-oroborates to a-silylstyrenes to give (Z )-PhCH=CHAr. A BF4 -mediated vyw-elimination of silicon and palladium has been suggested to account for the stereochemistry457. 

Palladium-monophosphine complexes catalyse trans-selective arylative, alkenyla-tive, and alkylative cyclization reactions of alkynals [e.g. (68)] and alkynones with organoboronic reagents. These reactions afford six-membered allylic alcohols (69) (g) and/or their five-membered counterparts (70), whose ratios are dramatically affected... 

Both routes actually use vanilly alcohol 34 (3-methoxy-4-hydroxybenzyl alcohol) as the starting material. Application of method (a) requires that 34 could be trimerized to C3-cyclotriguaiacylene, 5 (Table 1). However, as was said above, this reaction does not work, presumably because the phenolic group makes the molecule too reactive under the strong acidic conditions employed the allyl protected derivative 35 was thus used instead of 34 itself, and, on reaction with perchloric acid in methanol, gave the tris-allyl protected derivative 9 in 55% yield. Palladium catalysed cleavage of the allyl groups then led to the desired racemic triphenol 5. The latter could eventually be resolved by separation of its dia-stereoisomeric esters with co-camphanic acid [13]. 

Treatment of the diamide 77 with dibutyltin dichloride affords the 2,2-bis(2-[4(/ ),5(5)-diphenyl-1,3-oxazolinyl])propane 78, while successive reaction of 77 with mesyl chloride and aqueous ethanolic sodium hydroxide yields the diastereomer 79 <96TI3649>. The (+)- and (-)-forms of the chiral oxazoline 80 were used as ligands for palladium catalysed allylic amination reactions thus the acetate 81 and benzylamine gave the optically active amine 82 in excellent enantiomeric excess <97JOC55Q8>. The enantioselective catalytic alkylation of aldehydes RCHO (R = n-heptyl, Ph, cyclohexyl or PhCH=CH) with allyluibutyltin in the presence of chiral bis(oxazolinyl)zinc complexes, c.g., 83, leads to alcohols 84 in 40 6% enantiomeric excess <97TL145>. 

Reaction of the alkenyl iodide with a lithium organocuprate, or with an organometallic species in a palladium-catalysed coupling, gives the corresponding substituted allylic alcohol (in which the substituents originally present in the propargylic alcohol are trans to each other). This method is applicable to a variety of synthetic problems in which the stereoselective introduction of a trisubstituted carbon-carbon double bond is involved. For example, it formed a key step in a synthesis of juvenile hormone (2.64). 

Deoxymannojirimycin has been synthesized with excellent diastereoselec-tivity in a process based upon a palladium(II)-catalysed cyclization of an allylic alcohol 62 derived from D-mannitol. C-6 Homologues of 1-deoxynojirimycin and 1-deoxy-L-idonojirimycin (l,5,6-trideoxy-l,5-imino-D-gf/Mco- and -h-ido-heptitols) have also been prepared using palladium chemistry. In these reports the protected aminohex-l-enitol 63, derived from methyl a-D-glucopyranoside, was amino-carbonylated in the presence of palladium(II) chloride to afford a mixture of cyclized products whose composition was dependent upon the reaction conditions utilized. Two of these products, 64 and 65, were reductively transformed into the DNJ and 1-deoxy-L-idonojirimydn homolgues respectively 58,59... 

Berthiol, F, Doucet, H. and Santelli, M. (2006) S3mthesis of j8-aryl ketones by tetraphos-phine/palladium catalysed Heck reactions of 2- or 3-subslituted allylic alcohols with aryl bromides. Tetrahedron, 62,4372-83. 

Four reviews on allylic substitution reactions have been published. The first deals with the enantioselective allylic substitutions by carbon nucleophiles, in the presence of both palladium and non-palladium catalysts. The second reviews stere- 0 oselective allylic substitution reactions forming asymmetric C-C, C-N, and C-O bonds. The third review covers new developments in metal-catalysed asymmetric 0 allylic substitution reactions with heteroatom-centred nucleophiles. Several applications of this new methodology are included. Finally, the catalytic 5 2 and 5 2 reactions of allylic alcohols, most of which occur with a very high ee, have been reviewed. ... 

A similar Nicolas-Pauson-Khand combination was used in a synthesis of the ketone analogue of biotin 7.98, required for biochemical studies (Scheme 7.25). In this case, the Nicholas reaction was intermolecular, between allyl thiol as the nucleophile and carbocation 7.94 generated from alcohol 7.93. The Pauson-Khand reaction was then between the dicobalt complexed alkyne 7.95 and the double bond from the thiol moiety. The Pauson-Khand reaction proceeded with no stereoselectivity, and the diastereoisomers had to be chromatographically separated at a later stage. The synthesis was completed by reduction of the alkene of cyclopentenone 7.96, without using palladium-catalysed hydrogenation due to the sulfide moiety, and ester hydrolysis. 

Variously substituted allylic alcohols react with pyrazol-5-ones forming 4-substituted pyrazol-5-ones in yields ranging from 60 to 99% with 66 to 97% ee. The reactions are catalysed by a palladium complex with a chiral phosphoramidite ligand and a chiral phosphoric acid in THF (tetrahydrofuran) at 10 °C. 

The Pd(MeCN)4(BF4)2-catalysed conversion of allylic alcohols into allylic silanes and boronates has been investigated by product studies, kinetic studies, and H, B, F, and Si NMR (nuclear magnetic resonance) spectroscopy. The two reactions that occur by the same mechanism involve the formation of a palladium allylic alcohol [(a -allyl) palladium] complex after the alcohol is activated by BF3 formed from a BF4 ion of the catalyst. Then, a rate-determining, stereoselective transmetalation with Si(Me)2 and a reductive elimination of the palladium gives the linear silane. B2pin2 replaces Si(Me)2 in the borylation reaction. 

Negishi and his co-workers have developed several approaches to allylated arenes involving cross-coupling reactions. Preliminary studies established that aryl-aluminium, zirconium, or zinc compounds readily undergo palladium-catalysed cross-coupling with allylic halides or acetates (Scheme 19). Later in the year it was shown that allylic alcohol derivatives containing OAlR2,... 

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