25618-01-3Relevant academic research and scientific papers
Hydroxy-directed regio- and diastereoselective ene reaction of singlet oxygen with chiral allylic alcohols
Adam, Waldemar,Nestler, Bernd
, p. 5041 - 5049 (1993)
The photooxygenation of chiral allylic alcohols 1a, (Z)-1f-k, ethers 1b-d, and acetate 1e gave the corresponding hydroperoxy homoallylic alcohols and derivatives 2 through the ene reaction with singlet oxygen. While the reaction of the acetate le proceeded eryrthro-diastereoselectively as a result of the classical cis effect, for the allylic alcohols la and (Z)-1f-k, in which an alkyl group is located cis to the hydroxy-bearing substituent, high threo selectivity was observed. This finding is explained in terms of coordination of the nucleophilic hydroxy functionality of the stereogenic center with the incoming electrophilic singlet oxygen enophile. The stereodifferentiation is a consequence of the preferred conformation of the allylic alcohol for oxygen transfer, which is mainly determined by 1,3-allylic strain, while the influence of 1,2-allylic strain is small. A similar sensitivity toward both types of allylic strain is observed in epoxidations with m-CPBA, for which stereocontrol by cooperation of hydroxy-coordination and allylic strain is established. These similarities were convincingly demonstrated for the chiral allylic alcohol (Z)-1g as a novel stereochemical probe. Moreover, from these results it can be concluded that the optimal C=C-C-O dihedral angle of the allylic alcohol in the transition state for the singlet oxygen ene reaction lies between 90° and 130°. In addition to the threo selectivity with which the hydroperoxy moiety is introduced, the newly formed allylic double bond in the hydroperoxide is exclusively formed in the E configuration, as exemplified for the chiral allylic alcohol (Z)-1k; again, allylic strain in the 1O2 ene reaction is responsible.
Highly diastereoselective synthesis of 2-substituted-1,3-diols catalyzed by ketoreductases
Kalaitzakis, Dimitris,Smonou, Ioulia
experimental part, p. 9431 - 9439 (2011/01/12)
The stereoselective reduction of α-substituted-β-hydroxy ketones for the preparation of the corresponding optically pure 2-monosubstituted or 2-disubstituted-1,3-diols is described. These transformations proceed in high optical purities and yields. Ketoreductases were able to catalyze the formation of either the syn or the anti diol, depending on the enzyme. By replacing the α-alkyl substituent for an OAc moiety, in low conversion time (≤24 h), ketoreductases catalyzed the formation of the OAc-protected 1,2,3-triol, in high yield and with high optical purity (>99% de, >99% ee). This is a simple and highly stereoselective method for the synthesis of different diastereomers of chiral diols.
Synthesis of valuable chiral intermediates by isolated ketoreductases: Application in the synthesis of α-alkyl-β-hydroxy ketones and 1,3-diols
Kalaitzakis, Dimitris,Rozzell, J. David,Smonou, Ioulia,Kambourakis, Spiros
, p. 1958 - 1969 (2007/10/03)
Regio- and stereoselective reductions of α-substituted 1,3-diketones to the corresponding β-keto alcohols or 1,3-diols by using commercially available ketoreductases (KREDs) are described. A number of α-monoalkyl- or dialkyl-substituted symmetrical as well as non-symmetrical diketones were reduced in high optical purities and chemical yields, in one or two enzymatic reduction steps. In most cases, two or even three out of the four possible diastereomers of α-alkyl-β-keto alcohols were synthesized by using different enzymes, and in two examples both ketones were reduced to the 1,3-diol. By replacing the α-alkyl substituent with the OAc group, 1-keto-2,3-diols, as well as 1,2,3-triols were synthesized in high optical purities. These enzymatic reactions provide a simple, highly stereoselective and quantitative method for the synthesis of different diastereomers of valuable chiral synthons from non-chiral, easily accessible 1,3-diketones.
