Aminoalcohols lactones

Saponification of the ester provided 39 as a cyclohexylamine salt. The functionalization at C4 and C5 to install the necessary vicinal aminoalcohol begins with a selective halolactonization reaction of 39 to give lactone 40, bearing the incorrect alcohol stereochemistry at C4, and a rather challenging stereochemistry at C5, which would require the amino group be installed with retention at the C5-Br bond. Both issues are remedied by treatment of 40 with lithium hydroxide to generate an intermediate epoxide with inversion at C5, which, upon acidification, opens with inversion at C4 to give the y-lactone 41.37... 

In a subsequent communication, Takano et al. (276) reported an alternative synthesis of (+)-quebrachamine from the lactone 433, together with a synthesis of (-)-quebrachamine (5) from the same lactone, which was achieved by reversing the roles of C-2 and C-4. The new synthesis of (+)-quebrachamine essentially involved an alternative route for the conversion of the tetracyclic lactam 436 into the familiar tetracyclic aminoalcohols... 

Pete and coworkers [996,997,998] have generated prochiral dienols 4.12 by photoreactions of a,P-unsaturated esters and lactones bearing a proton in the y-position. Asymmetric protonation of 4.12 is performed at -45°C with catalytic amounts of aminoalcohols such as 1.9 (R = NHi-Pr or NHCH2Ph) (Figure 4.7). Good selectivities are observed only if the a,P-unsaturated ester bears a tertiary carbon in the y-positioa... 

The percentage of ee does not depend on the conversion yield and the aminoalcohols can be recovered unchanged in the photodeconjugation of esters and lactones. A study of the dependence of the enantioselectivity of the photodeconjugation of esters in nonpolar solvents as a function of concentration of the chiral inductor (Fig. 2), indicated that very small amounts of the inductor are needed. 

Enantioselective photodeconjugation occurs with lactones, esters, and conjugated enones [33]. In principle, as soon as a prochiral photodienol can be produced, an enantioselective protonation is expected in the presence of a chiral -aminoalcohol. However, the corresponding acids and amides are unsuitable starting materials for enantioselective photodeconjugation. 

Scheme 4. Unsaturated lactones, esters, enones and -aminoalcohols considered in enantioselective photodeconjugation reactions.

A collection of results obtained with the most effective catalyst systems is summarized in Figure 6.4. Noteworthy examples include the oxidation of a-aminoalcohols with no loss in enantiopurity and the oxidation of cis-allyhc alcohols without Z E isomerization. Stahl also demonstrated the chemoselective oxidation of primary diols to form lactones [22]. While ABNO provides efficient oxidation of symmetric diols, TEMPO discriminates between subtle steric differences in nonsymmetrical substituted diols. Cu/nitroxyl catalysts have also been applied to a variety of tandem reactions [23], perhaps the most noteworthy of which is the conversion of primary alcohols to nitriles via in situ condensation of ammonia with the aldehyde and subsequent dehydrogenation of the primary imine to the nitrile (Figure 6.5) [24]. 

The a-aminoalcohol hydroxy group attacks the other ester, forming a lactone. 

Optically active allylboronates bearing chiral auxiliary located at the boron atom found widespread applications in asymmetric synthesis. Enantiomerically enriched a-alkylidene-y-lactones and lactams can also be synthesized following such a synthetic approach. VUlieras et al. (41, 45] demonstrated the potential of chiral allylboronates derived from 2-phenyl-2,3-bomanediol, ephedrine, or norephedrine for this purpose. Chiral allylboronates 46a,b were obtained in a sequence of reactions involving transformation of achiral precursors 32 into the corresponding boronic acids 44 followed by their esterification with enantiomerically pure diol or 1,2-aminoalcohol 45 (Scheme 4.10). In the case of methyl-substituted derivatives 32b (R = Me), initial composition of E- and Z-isomers was transferred to the target allylboronates 46b. Importantly, the isomeric mixture was separated by means of the column chromatography. 

Novel functionalized peroxides which may be used as UPR curing agents as well as initiators for polymerization reactions and as monomers for polymerizations to form peroxy-containing polymers were elaborated [162]. Initiators may be prepared by reacting hydroxy-containing tertiary hydroperoxides with diacid halides, dichloroformates, phosgene, diisocyanates, acid anhydrides and lactones to form the functionalized peroxides. These reaction products may be further reacted, if desired, with dialcohols, diamines, aminoalcohols, epoxides, epoxy alcohols, epoxy amines, diacid halides, dichloroformates and diisocyanates to form additional fimctionalized peroxides. The use of monoperoxyoxalates of the structure (Scheme 24) as initiators... 

Diethyl zinc in combination with a chiral aminoalcohol and oxygen as oxidant afforded lactone 46 with up to 32% ee in good yield from 3-phenylcyclobutanone (50) [Eq. (17)] [344]. Applying the Sharpless/Katsuki titanium-based epoxidation system to related substrates gave products with both moderate enantioselectivities and yields [345]. 

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