Boc protected amino alcohol

Study of the Pd(0Ac)2/DMS0/02 system by van Benthem and co-workers t i f has opened a route to oxazolidine derivatives from alkenes bearing A-Boc-protected amino alcohols (Scheme 16). The oxazolidines obtained can readily be converted into A-Boc-protected /3-amino alcohols through anodic oxidation and hydrolysis. 

The synthesis of ( )-preussin has been achieved using a similar type of carboamination reaction strategy in six steps with 15% overall yield. After the ozonolysis and addition of Li-vinyl cuprate, two diastereomers of O-TBS and A-Boc-protected amino alcohol were obtained, (-l-)-preussin was synthesized from the anti diastereomer, and the 5y -diaster-eomer was used for the synthesis of ( )-3-epf-preussin (Scheme 40.22). 

Gallagher et al. reported on various IV-heterocycle construction via cyclic sulfamides. Using this strategy, they synthesized enantiopure 1,4-benzoxazine 311, which was the precursor of the blockbuster antibiotic levolloxacin 312 (Scheme 40.67). Starting from Boc-protected amino alcohol 305, sulfamidate 306 was prepared using RuCU and NaI04. 306 was treated with halo phenol 308 followed by acidic hydrolysis to afford amino ether 310. The compound 310 underwent Pd-catalyzed C—N alkylative cyclization to produce benzoxazine 311, which was the potential precursor from which Levolloxacin 312 can be synthesized. 

Good to excellent diastereoselectivities have been reported when 2-(trimethylsilyl)thiazole (3), an effective equivalent of an aldehyde group, is used as nucleophile24,27. Thus, addition to TV-Boc-protected amino aldehydes in dichloromethane at — 30 C afforded mixtures of amino alcohols in comparatively good yields with reasonable syn selectivity. However, the stereoselectivity decreased substantially when the reaction was carried out in tetrahydrofuran at 25 °C. 

The first step in the overall synthetic scheme (Scheme 6) is the condensation of an appropriate carboxylic acid with trifluoroacetaldehyde. The carboxylic acid is chosen to impart specificity for the target enzyme. In one example,[28 the dianion of cyclohexanepropanoic acid (29) was formed by the addition of LDA and then quickly condensed with trifluoroacetaldehyde to form the p-hydroxy acid 30 as a racemic mixture of erythro- and threo-isomers. The p-hydroxy acid 30 is then protected with TBDMSOTf forming 31. Diphenyl phosphorazidate, TEA, and benzyl alcohol were then utilized in a Curtius rearrangement of the protected alcohol 31, which proceeds through an isocyanate intermediate that yields the protected amino alcohol 32 upon reaction with benzyl alcohol. In order for this step to occur at an appreciable rate, a second equivalent of triethylamine had to be added. The amino alcohol 32 was then deprotected and coupled with Boc-Phe-Leu-OH to give the trifluoromethyl alcohol 33, which was oxidized to the corresponding trifluoromethyl ketone 34 as a 1 1.2 mixture of diastereomers using the Dess-Martin periodinane procedure. Thus far, the compound shown in Scheme 6 is the only compound that has been synthesized by this method, but it is reasonable to assume that many other similar fluoro ketones can be produced by this scheme. 

Although more rare, the ring opening of A-acyl (3-lactams has also been realized by using hydrides, giving rise to the corresponding reduction products. In this context, Scheme 40, Lee and Pak [107] have described the treatment of A-Boc (3-lactam 119 with lithium aluminium hydride to give A-protected amino alcohol 120. Compound 120 could serve as potential intermediate for the synthesis of various hydroxylated indolizidine alkaloids. 

In an alternative route,2 Boc-protected amino acids are reduced to the protected amino alcohol with borane-THF (45-95% yield) and pyridinium dichromate is used for oxidation to the aldehyde (75-90% yield). The optical rotations of the aldehydes obtained by these two procedures differ considerably, presumably owing to racemization encountered in the PDC oxidation. 

Due to the easy removal of the byproducts, B0C2O (65) can also be used for the acylation of amino acids (Scheme 29) or peptide esters in organic solvents.Amino acid esters or their respective hydrochlorides react sluggishly when the reaction is performed in alcohols with sodium hydrogen carbonate as a solid, poorly soluble base. Sonication increases reaction rates leading to Boc-protected amino acid esters in good to quantitative yields within few hours instead of more than 24 hours. 

Dias et al. reported that the oxidation of Al-Boc-protected homoallylic alcohols with OsOq as a catalyst in the presence of NalOq efficiently occurred in Et20 H20 (1 1) to provide 4-N-Boc-amino-3-hydroxy ketones in high yields (eq 73). ... 

Simple sensors such as 3,3 -dibenzoyl-BINOL 22 and its dimethylated analog (Fig. 6) were recently reported to give enantioselective quenching by a variety of molecules, namely Boc-protected amino acids, hydroxy acids, and amino alcohols, with a maximum selectivity K IK of 7.72 for Boc-Phe [62]. A PET process was also proposed in this case, in analogy with previous studies on anion binding. 

BINAP-Ru is effective for the diastereoselective hydrogenation of some chiral yS-keto esters (Fig. 32.13). Reaction of N-Boc-protected (S)-y-amino / -keto esters 13A catalyzed by the (R)-BINAP-Ru complex results in the syn alcohols 13B exclusively [52]. The stereocenter at the / -position is controlled by the chirality of the catalyst therefore, use of the S catalyst affords the anti isomer, as predicted. Derivatives of statine, a key component of the aspartic proteinase inhibitor pep-... 

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