Protecting moieties allyl

We have also studied the effect that moving the double bond closer to the amino acid moiety has upon the reactivity of unsaturated a-amino acids [43]. To this end, the cross-metathesis reactions of similarly protected homoallyl-, allyl-and vinylglycine with oct-l-ene were investigated under identical conditions (Eq. 25) (Table 3). 

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-... 

The first synthesis, by method a, of amylostatin (XG) was reported by Kuzuhara and Sakairi. The synthon for the cyclohexene moiety was the benzylated allyl bromide 382, derived from D-glucose by the sequence 378 — 382 of the Perrier reaction. The coupling reaction of 382 using an excess of 4-amino-T,6 -anhydro-4,6-dideoxymaltose tetrabenzyl ether (383), and sodium iodide in DMF for 3 days produced a mixture of the epimeric monocarba-trisaccharide derivatives, separation of which gave the protected derivatives in 15% yield. 

Allylation and subsequent protection of the thus formed hydroxyl group furnishes compound 134, which bears the C-ring skeleton of baccatin HI. Removal of the C-9 silyl group, PhLi treatment of the resulting hydroxyl ketone, and in situ acetylation provides compound 135, which has the C-2 benzoate functionality. In the presence of a guanidinium base, equilibrium between the C-9 to C-10 carbonyl-acetate functional groups can be established. Thus, the desired C-9-carbonyl-C-10-acetate moiety 136 can be separated from the mixture. Compound 136 is then converted to aldehyde 137 via ozonolysis for further construction of the C-ring system (Scheme 7-40). 

The allylic HYCRAM derivative was subsequently modified by insertion of a standard amino acid between the aminomethyl resin and the hydroxy butenoic acid moiety. Using this allylic anchor, the resin-linked, glycosylated HIV peptide T-derivative 164 was synthesized by application of Fmoc amino protection and sidechain protection with lert-butyl groups. The lac-tosamine peptide T (165) could be released from the resin by application of the palladium(0)-catalyzed allyl-transfer reaction to V-methyl aniline as the allyl acceptor. 

A further eight steps were required to convert the cyclopentanone 52 into the sulfone 59 that was deprotonated and treated with an allylic bromide (60) to afford the alkylated sulfone 61 (Scheme 7). The sulfone moiety and the benzyl ether protecting group were reductively removed in a one-pot procedure to afford a mono-protected diol (62). 

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

Two consecutive enolate alkylations were utilized to generate the quaternary carbon atom (Scheme 38). Alcohol 238 was transformed into the protected hydroxy enone 244. Regioselective deprotonation at the a-position of the ketone 244 led to a cross-conjugated enolate that was alkylated with the allylic iodide 245. The vinyl silyl moiety in 245 represents a masked keto group [127]. The choice of the TBS protecting group for the hydroxyl group at of 244 was crucial in order to prevent the deprotonation at the y-posi-... 

Despite the use of protecting group strategies, compounds containing amino moieties are often plagued with poor reactivities in CM. For instance, the CM reactions of unsubstituted allylic carbamates typically proceed in low yields (Scheme The predominant side-products obtained in these reactions are alkene homodimerization and... 

Mori has reported the nickel-catalyzed cyclization/hydrosilylation of dienals to form protected alkenylcycloalk-anols." For example, reaction of 4-benzyloxymethyl-5,7-octadienal 48a and triethylsilane catalyzed by a 1 2 mixture of Ni(GOD)2 and PPhs in toluene at room temperature gave the silyloxycyclopentane 49a in 70% yield with exclusive formation of the m,//7 //i -diastereomer (Scheme 14). In a similar manner, the 6,8-nonadienal 48b underwent nickel-catalyzed reaction to form silyloxycyclohexane 49b in 71% yield with exclusive formation of the // /i ,// /i -diastereomer, and the 7,9-decadienal 48c underwent reaction to form silyloxycycloheptane 49c in 66% yield with undetermined stereochemistry (Scheme 14). On the basis of related stoichiometric experiments, Mori proposed a mechanism for the nickel-catalyzed cyclization/hydrosilylation of dienals involving initial insertion of the diene moiety into the Ni-H bond of a silylnickel hydride complex to form the (7r-allyl)nickel silyl complex li (Scheme 15). Intramolecular carbometallation followed by O-Si reductive elimination and H-Si oxidative addition would release the silyloxycycloalkane with regeneration of the active silylnickel hydride catalyst. 

The Pd(0)-catalyzed transfer of the allyl moiety to dimedone [23], morpholine [22], or N,N -dimethyl barbituric acid [27] resulted in the completely selective cleavage of the Aloe group, whereas the numerous other protecting groups and the glycosidic bonds,... 

In a different sequence of reactions, N-acetylation of 274 and exposure of the intermediate imide 275 to ethanolic KOH gave a mixture (about 2 1) of the desired carboxylic acid 276 together with the starting lactam 274 via the non-selective hydrolysis of the imide moiety of 275 (148a,c). When 276 was treated with /V-bromosuccinimide (NBS), an intermediate bromolactone was produced which was heated at reflux in pyridine in the presence of DBU to give 277. The conversion of the lactone 277 to the lactam 278 was effected by heating 277 in aqueous NaOH followed by protection of the resulting allylic alcohol function as a tetrahydropyranyl ether. 

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