Benzyloxy compounds

Turning our attention to disubstituted benzyloxy compounds, we found that they in general were weaker except for the 2,6-02 and 2,6-F2 compounds. The activity-lowering effects of the meta or para substituents are seen in the 2,4- and 3,4 -disubstituted compounds. 

Both benzyl-oxygen and nitrogen-oxygen bonds are present in N-benzyloxy compounds and can be hydrogenolyzed. Because of the greater reactivity of benzylic compounds, the benzyl-oxygen bond can usually be made to cleave selectively on Pd/C in MeOH (Scheme 4) [44]. 

The method was applied to the synthesis of evodionol (Table 12.1) by the reaction of the methyl ether of phloroacetophenone shown, to give the chromene in 65% yield (95% on the intermediate used). In the much longer synthesis of evodionol (ref. 39), at the initial step by the Hoesch reaction on 2,2-dimethyl-5,7-dihydroxychroman, the desired 6-acetyl product was the minor one and following benzylation to give the 7-benzyloxy compound, methylation, hydrogenolysis and DDQ oxidation were the required remaining steps. 

Benzylthio or 2-benzyloxy derivatives of A-2-thiazoline-5-one (224) are readily opened by amines to give the amide derivatives (225) (Scheme 115) (459. 471). Compound 225 can be cyclized thermally to the corresponding thiohydantoins (459). Similarly, treatment of 4-substituted-2-phenylthiazol-5(4H)-ones (226) with amino acids, peptides, or hydrazine affords the corresponding Nfcti-thiobenzamidoacetylated derivatives (227) (Scheme 116) (455). 

In the area of medicinal chemistry, Haemers and coworkers synthesized a series of 4 -hydroxy-3-methoxyflavones that exhibited antiviral activity against poliomyelitis and rhinoviruses. A representative number of compounds is shown below. First, O-hydroxyacetophenones 61 were converted to the corresponding flavones 64 using standard conditions in yields of 74-92%. Cleavage of the benzyloxy groups of 64 was then achieved under acidic conditions to deliver the requisite flavones 65. 

Electrochemically generated nickel is very selective for the reduction of ai compounds into anilines, in which alkenyl, alkyhyl, halo, cytino, formyl, ind benzyloxy groups are not affected. Sodium snlfide has been used for the selective reduction of at group in the presence of aliphatic nitro groups (Tq. 6.44. ... 

Our journey begins with the photo-induced union of 3,4-dimethylfuran (19) and / -(benzyloxy)-propanal (18) (see Scheme 5). Irradiation of a solution of these two simple, achiral compounds in benzene with a 450 W Hanovia lamp equipped with a vycor filter results in the exclusive formation of head-to-head, exo photoadduct 17 in 63% yield. As a cw-fused dioxabicyclo[3.2.0]heptene system, intermediate 17 possesses a folded molecular framework to which access is obstructed on the concave face. In the presence of mCPBA, the less hindered convex face of the enol ether double bond is oxidized in a completely diastereoselective fashion, affording intermediate 16 in 80% yield after regioselective opening of... 

In the ( )-series, e.g., ( )-5-benzyloxy-3-hexen-2-one, the ano-compound 3a was the major isomer. This can be rationalized based on the Felkin model ... 

Chiral tricyclic compounds have been prepared by thermal and Eu(fod)j-catalyzed cycloadditions of furanosidic a,-unsaturated aldehydes 26-29 (Figure 3.4) with cyclopentadiene (18) [31]. The diastereofacial selectivity depends markedly on the stereochemistry of the anomeric benzyloxy and methoxy groups. 

J ,3J ,4J ,5J )-2,5-bis(benzyloxy)-3,4-dihydroxy-Nd -bis (lS)-2-methyl-l-[(methylamino)carbonyl]propyl hexanediamide is a C2-symmetric HIV-1 protease inhibitor [29]. Derivatization in the para positions of the benzyl-oxy groups via microwave-assisted Stille reaction on the corresponding di-brominated inhibitor smoothly yielded the desired heteroarylated derivatives (Scheme 10). Interestingly, the 1,3-thiazole derivative showed a higher antiviral activity on the wild type virus than the lead compound. The activity remained at the same level in the presence of seriun. Unfortimately, a low activity was observed on mutants. 

This effect is seen in the case of ketone 4, where the stereoselectivity of the benzyloxy derivative is much higher than the compound lacking the benzyloxy group.110... 

Both benzyl-oxygen and N-O bonds can undergo hydrogenolysis in the compounds containing benzyloxy-nitrogen bonds,... 

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