Benzyl tetramates

The Painter group developed another approach to tetramates (e.g., 320) that involved the reductive amination of y-oxobutenoates (e.g., 319) in the presence of primary amines (Scheme 81 2002S869). Unsaturated dicarbonyl 319 was prepared in three steps by the phosphine-catalyzed Michael addition of benzyl alcohol to butynoate 318, desilylation, and oxidation of the resulting primary alcohol with 2-iodoxybenzoic acid (IBX). Treatment of 319 with tert-butylamine followed by sodium borohydride gives the O-benzyl tetramate 320 via a reductive amination—lactamization. 

In our group, several dendrimers based on ( R)-3-hydroxybutanoic acid (HB) have been prepared [56-58]. The dendrimers were synthesized by the convergent strategy. Trimesic acid has been used as core unit and the benzyl esters of the dimer and the tetramer of HB as elongation units. In such a way dendrimers of 1st and 2nd generation (27-30) have been constructed (Fig. 13). Since poly(.R)-3-hydroxybutanoic acid (PHB) is known to be biodegradable [59, 60] the stability of the dendrimers 27-30 was tested in the presence of PHB-de-... 

Arylalkenes can undergo various reactions when treated with sodium, since compounds such as a-methylstyrene are both olefins with allylic hydrogens and styrenes, both of which are reactive. The reaction of a-methylstyrene with sodium has been reported by Bergmann et al. (6i) to yield tetramers. More recent work by Kolobielski and Pines (56) has shown that dimers and products derived from dimers are formed when this compound is heated with a sodium-benzyl-sodium catalyst. Some of the major products were cumene (VII), p-terphenyl (VIII), and 1-methyl-1,3-diphenyl-cyclopentane (IX). 

In solution lithium alkyls are extensively associated especially in non-polar solvents. Ethyllithium in benzene solution exists largely as a hexamer (9, 43) in the concentration range down to 0.1 molar and there is no evidence for a trend with concentration so presumably the hexamers persist to even lower concentrations. Indeed even in the gas phase at high dilution it exists as hexamer and tetramer in almost equal amounts (3). In a similar way n-butyllithium in benzene or cyclohexane is predominantly hexameric (62, 122). t-Butyl-lithium however is mostly tetrameric in benzene or hexane (115). In ether solution both lithium phenyl and lithium benzyl exist as dimers (122) and it has been suggested that butyllithium behaves similarly in ether (15) although this does not agree with earlier cryoscopic measurements (122). It is however certain that more strongly basic ethers cause extensive breakdown of the structure. 

There is again an obvious correlation between reaction order and degree of association. The one quarter order for methyllithium could be explained satisfactorily by the usual assumption that the reactive species is methyllithium monomer in equilibrium with its tetramer. For phenyllithium a partial dissociation would lead to an order between one half and unity, as observed, if the dissociated product only were active. Other schemes involving some reactivity of both species would be equally plausible [101]. The first order behaviour with benzyllithium would require that the major reactive species is the ion-pair and not the free benzyl anion which must be present in small concentration. 

Oligomerization of a 7-amino-2,6-anhydro-7-deoxy-heptonic acid results in mimetics of (1 6)-linked sugars with a three-atom instead of a two-atom linker. The sulfated tetramer 24 (O Scheme 7) turned out to exhibit /x-molar activity in the protection of MT2 cells from HIV infection [33], and was also shown to provide heparanase inhibitory activity [34]. With different location of the amide bond, a still benzyl protected /3(1 6)-linked octamer of glucosyl-uronic acid-methyl amine (Gum [35]) 25 was synthesized [36]. 

These compounds are less aggregated in solution. For instance, 2,2-dibutyl-l,3,2-dioxastannolane, a polymer in the solid state, has been shown, by variable temperature Sn NMR spectroscopy, to be a mixture of dimers, trimers, and tetramers in solution, with dimers predominating at room temperature and above. This technique has also indicated that most carbohydrate-derived stannylene acetals are present predominantly as dimers in solution." " " Supporting evidence has been obtained from mass spectral studies and by comparison of solid-state NMR spectra with those of solutions." Some dibutylstannylene acetals derived from cw-diols contain an observable proportion of higher oligomers benzyl 4,6-0-benzylidene-2,3-0-dibutylstannylene-o -D-mannopyranoside is present as a mixture of a dimer and a trimer in chloroform-d at -60 °C but, in the less polar solvent toluene-dg, is mainly present as a tetramer at that temperature. ... 

Wessel later used solid phase synthesis to prepare a tetramer of amido-linked 2-amino-2-deoxyglucuronic acids [50]. In that disclosure, benzyl 2-fiuoren-9-ylme-... 

Some unusual reactions for preparation of peraza-crowns need to be mentioned. Aziridine molecules readily polymerize and, in some cases, macrocycles can be isolated. For example, 1-benzylaziridine reacted to give good yields of the tetra-A -benzyl-substituted peraza-12-crown-4 (Ham, 1980 Hansen and Burg, 1968 Kossai et al., 1980). These cyclic tetramers were formed... 

Fleming and Ghosh synthesised nonactin by cyclisation of the linear tetramer 335 assembled from methyl (+)-nonactate and benzyl (-)-nonactate (Scheme 44) (75). The O-protected (+)-nonactic... 

Fleming and Ghosh also synthesised nonactin by cyclodimerisation of the acid derived from the benzyl ester 343 (=334) using Yamaguchi conditions (Scheme 47) (75). Nonactin was isolated in lower yield than by the linear tetramer method, presumably because of the problem of "dimer" and oligomer formation. 

The stereochemical outcome of the alkylation process also depends on the nature of the base used to generate the carbanion. Use of the substrates 297 (R = NPr 2, = Me or PhCH2) with Ida-thf-R X gave 86-94% of the meso compound 301. On the other hand, the benzylation of 298 (R = NPr 2, R = PhCH2) gave only 302 when lithium tetram-ethylpiperidide was used, but mixtures of299 and 302 in the ratio 18 82 (Ida used) or 80 20 (BuLi used). ... 

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