Pd -catalyzed allyl transfer

As has already been detailed for the allyloxycarbonyl (Aloe) moiety, allyl esters also proved to be very versatile and useful carboxy-protecting groups. They can be easily constructed by azeotropic esterification or nucleophilic displacement on allylic halides. For the cleavage of these esters lithium di-methylcuprate can be used. However, a much milder method is found in the Rh -catalyzed isomerization of the allyl moiety to a propenyl ester which immediately hydrolyzes under the reaction conditions (Scheme 67). Even milder is the Pd°-catalyzed allyl transfer to morpholine as an accepting nucleophile. The removal of allyl ester protection has earlier been used in particular in -lactam anti-... 

An allyl carbonate linker 2k has been used [122] to synthesize pseu-doargipinine III on a 4-methylbenzhydrylamine base resin (to which alanine had been attached as a spacer and internal standard). The nitrophenylallyl carbonate was prepared from the allyl alcohol and used to anchor mono-protected diamines. During further synthetic steps the anchoring group was shown to be stable toward concentrated TEA solutions and piperidine but could be efficiently cleaved by Pd-catalyzed allyl transfer. 

The regiochemical control of Pd-catalyzed hydnde transfer reacdon is much more effeedve than that of the radical denitradon, as Shown in Eq 7 98 The base-catalyzed reacdon of nitroolefins with aldehydes followed by denitradon provides a new syntbedc method of homoallyl aicohols fEq 7 99 Exomethylene compounds are obtined by denitradon of cyclic allylic nino compounds with PdfO, HGO-,H and Et- N fEq 7 100 ... 

The regiochemical control of Pd-catalyzed hydride transfer reaction is much more effective than that of the radical denitration, as shown in Eq. 7.98. The base-catalyzed reaction of nitroolefins with aldehydes followed by denitration provides a new synthetic method of homoallyl alcohols (Eq. 7.99).140 Exomethylene compounds are obtained by denitration of cyclic allylic nitro compounds with Pd(0), HC02H and Et3N (Eq. 7.100).140b... 

The alternative selective cleavage of the allyl ester was achieved by Pd(0)-catalyzed allyl transfer. Because the Fmoc group is sensitive to morpholine, a very weak base must be used as the allyl-trapping nucleophile. IV-Methyl aniline was favorable, and its use as a scavenger nucleophile gave rise to the acid 29 in a high yield. 

Allyl-based N"-protection, stable to base and moderate acid, can be achieved with the allyl group itself,or with an allyloxymethyl (Alom) group (Scheme 7).P4,34,5S] githej- gagg cleavage by Pd(0)-catalyzed allyl transfer to A,A -dimethylbarbituric acid l (which probably also scavenges the formaldehyde released from the latter) proceeds well, provided care is taken over the integrity of the catalytic complex. 

Protection by the A "-allyloxycarbonyl (Aloe) group (Scheme 11) is completely orthogonal with A -Boc but not with A -Fmoc because A "-Aloc, like A "-Z (see Section 2.6.3.3), is cleaved by nucleophiles such as piperidine it is stable to trifluoroacetic acid but is cleaved by Pd(0)-catalyzed allyl transfer to methylaniline in tetrahydrofuran/dimethyl sulfoxide or piperidine/dimethylformamide (1 1 ).P 1... 

The reaction scheme for substrates 16 bearing different substituents at the two allylic termini is more complex (Scheme 12). In this case 16 and the enantiomer ent-l6 are converted to different allyl complexes 18 and 19 with opposite absolute configuration at the allyl C-atoms. NucleophiHc addition to 18 with soff nucleophiles leads to the regioisomers 20 and 21 whereas 19 affords the corresponding enantiomeric products ent-20 and ent-2l. The two allyl complexes 18 and 19 cannot interconvert by a K-O-K process which solely results in syn-anti isomerization. Isomerization of 18 to 19 would be possible by Pd(0)-catalyzed allyl transfer (see Sect. 2.2.3) or a mechanism proposed for allyUc acetates involving metal-centered addition of acetate to the allyl system with retention... 

Scheme 12.17 1,5-Chirality transfer in Pd-catalyzed allylations of chelated enolates [33].

Allylic metal compounds useful for further transformations can be prepared by Pd-catalyzed reactions of allylic compounds with bimetallic reagents. By this transformation, umpolung of nucleophilic 7r-allylpalladium complexes to electrophilic allylmetal species can be accomplished. Transfer of an allyl moiety from Pd to Sn is a typical umpolung. 

The protected nucleoside-3-phosphoramidite monomer units such as 671 are used in the solid-phase oligonucleotide synthesis. In the 60mer synthesis, 104 allylic protective groups are removed in almost 100% overall yield by the single Pd-catalyze reaction with formic acid and BuNH2[432], N,(9-protection of uridine derivatives was carried out under pha.se-transfer conditions[433]. 

Hydroxamic acids constitute an important class of siderophores, which play a major role in iron solubilization and transport. Some of them are important as therapeutic agents. The Michael addition of nitroacetyl proline esters to allyl acrylate followed by Pd(0)-catalyzed intramolecular allyl transfer and subsequent reduction of the nitro group yields a novel class of cyclic hydroxamic acids related to pyroglutamic acid (Scheme 5.9).85... 

Propargylic mesylates such as fluorine-substituted derivative 265 react with PhZnCl in the presence of Pd(PPh3)4 (5 mol%) in THF at 0°C within 2 h to provide the anti-Si 2 product in excellent yield and complete transfer of the stereochemistry leading to the allene 266 (Scheme 78). Copper(I) catalyzed allylic substitutions with functionalized diorganozincs proceed with high 8 2 selectivity. Thus, the reaction of the chiral allylic phosphate 267 with 3-carbethoxypropylzinc iodide in the presence of CuCN 2LiCl (2 equivalents) furnishes the awf/-Sjv2 substitution product 268 in 68% yield. By the addition of w-BuLi (1.2 equivalents) and TMSCl (1.5 equivalents), the bicyclic enone 269 is obtained in 75% yield and 93% ee (Scheme 79) . 

Another method for deallylation is the Pd-catalyzed transfer of the allyl group to reactive nucleophiles. Sodium 2-ethylhexanoate [141], morpholine [142], dimedone [143] and AA-dimethylbarbituric acid [144] are used as allyl scavengers. It is claimed that benzenesulfinic acid 331 or sodium toluenesulfinate are the best allyl scavengers [145]. 

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