Hydroxymethyl side chain

The rhodium-catalyzed borylation of alkanes is applied to regiospecific functionalization of polyolefines.165,165a The reaction of polypropylenes (atactic, isotactic, and syndiotactic) with B2pin2 in the presence of Cp Rh( 74-C6Me6) catalyst at 200 °G affords the borylated polymers, which are treated with basic hydrogen peroxide in a mixture of THF and H20 to oxidize the boronate esters to the corresponding alcohols (Scheme 20). The hydroxylated polymers contain 0.2-1.5% hydroxymethyl side-chains. 

The hydroxymethyl side chain of 3-(2-benzofuranyl)-5-(hydroxymethyl)[l,2,4]triazolo[3,4-A][l,3,4]thiadiazole-6(5//)-thione 41 can be converted to chloromethyl derivative upon treatment with thionyl chloride amines can displace this chloride to provide the corresponding aminal 43 (Scheme 2) <1992IJB167>. 

The next residues were attached successively by dicyclohexylcarbodiimide-mediated coupling of Boc-amino acids with the free amino groups. The use of excess Boc-amino acid eliminated the need for capping after coupling. The last Boc-group and the benzyl-based side chain and carboxy-terminal protectors were removed at the end of the synthesis by acidolysis with hydrogen bromide in trifluoroacetic acid the latter was used instead of acetic acid to avoid acetylation of hydroxymethyl side chains (see Section 6.6). Catalytic hydrogenolysis of the peptide removed the nitro... 

The synthesis of l,5-dideoxy-l,5-imino-L-arabinitol (13), a derivative of (5) lacking the hydroxymethyl side chain at C-5 was reported [49]. This compound did not exhibit any appreciable activity with imspecified galactosidases. 

The composition of solutions of the 2-heptuloses has been determined, and discussed, by Angyal and Tran.92 These ketoses are different from other reducing sugars inasmuch as there are two hydroxymethyl side chains attached to the pyranose ring. In the a-pyranose form, they are cis to each other and will therefore both be equatorial in the preponderant chair form. In the / -pyranose, however, one or other of the hydroxymethyl groups has to be axial and, in consequence, the / anomers are disfavored in only one solution (that of the altro isomer) was the yS-pyra-nose detected in the 13C-n.m.r. spectrum.92... 

Table III presents the rotational analysis for compounds 3-7, in the three staggered orientations for the hydroxymethyl side chain to give conformers of types a, b, and c. The ranges in rotation expected for certain conformations results from the above-mentioned uncertainty in the value for OH/Or (exo).

A direct route to 5,8-disubstituted indolizidines and 1,4-disubstituted quinolizidines was reported by Barluenga and co-workers <02OL1971> (Scheme 30). Hetero-Diels-Alder reaction followed by reduction and desilylation gave good yields of the key piperidine core 51. Further elaboration of the hydroxymethyl side chain followed by RCM and hydrogenation gave the targets in moderate yields. 

A useful reagent has been introduced by Paulsen et al for the introduction of hydroxymethyl side chains. The dianion (10) formed by reactions of tributyl-stannyl-methanol with two equivalents of butyl lithium reacts with keto-groups, even in the presence of epoxide functions, to give the hydroxymethyl branch. For example, it reacted with the ulosides (11) and (12) to give the indicated products (Scheme 3). 

In cases where a 2-C-(hydroxymethyl)aldose is easily available via base-catalyzed aldolization of a 2,3-0-alkylidene-aldofuranose with formaldehyde, the carbon-skeleton rearrangement operating in the Bilik reaction can also be conveniently exploited for preparation of 2-ketoses. The method is especially advantageous for synthesis of heptuloses and octuloses as (1) in special cases the 2-C-hydroxymethyl side chain construction is simpler than the classical aldose chain elongations, and (2) the equilibrium of a 2-C-(hydroxymethyl)aldose and its corresponding 2-ketose in the Bilik interconversion is much more favorably shifted to the side of the latter sugar (always > 85%) than the LdB-AvE transformation of the pertinent unbranched aldose. 

FIGURE 7.71 Expansions of the ring proton resonances from the 300-MHz H NMR spectrum of furfuryl alcohol. The resonances from the hydroxymethyl side chain are not shown. 

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