Absolute stereochemical

Absolute Stereochemistry Absolute stereochemical assignment of each stereocenter (R vs S) Cahn-Ingold-Prelog Convention (sequence rules)... 

Scheme 4 outlines the synthesis of key intermediate 7 in its correct absolute stereochemical form from readily available (S)-(-)-malic acid (15). Simultaneous protection of the contiguous carboxyl and secondary hydroxyl groups in the form of an acetonide proceeds smoothly with 2,2 -dimethoxypropane and para-toluene-sulfonic acid and provides intermediate 26 as a crystalline solid in 75-85 % yield. Chemoselective reduction of the terminal carboxyl group in 26 with borane-tetrahydrofuran complex (B H3 THF) affords a primary hydroxyl group that attacks the proximal carbonyl group, upon acidification, to give a hydroxybutyrolactone. Treat-... 

WIN 64821 (10) and (—)-ditryptophenaline (11) syntheses [7], not only effectively differentiated the two amide moieties but also most importantly marked the first in a series of stereochemical transfer steps in which the stereochemistry of the constituent L-amino acids was relayed to ultimately define each of the relative and absolute stereochemical configurations at all eight stereogenic centers found in the target compound. Finally, /V-methylation of the base-sensitive amide in 77 % yield using methyl iodide and potassium carbonate in acetone completed the 5-step synthesis of our key tetracyclic bromide monomer starting from commercially available amino acid derivatives. 

Where possible, absolute stereochemical relationships in the reaction product are shown, although several papers do not have this data available. In those cases, stereochemistry has not been assigned. 

The enantiomeric purity of vinylsilane (S)-3a and (R)-3c are determined to be >95% ee by 1H-NMR (400 MHz) on the derived mandelate ester, obtained by a DCC-promoted coupling to (R)-O-acetylmandelic acid, and absolute stereochemical assignment is accomplished by 1H NMR analysis of the derived (R)-O-acetyl-mandelate esters. For details of this procedure see the published method of Trost.3... 

The absolute stereochemical assignments associated with Fi and are as illustrated in structures 159 and 160, respectively. 

The syn-configuration of the resulting aldols 4i and 42 can be deduced from the coupling constants in the H-NMR spectra (4.5 Hz), and the absolute stereochemical assignments were made by degradative removal of the hydroxyl group and correlation of the resulting a-substituted carboxylic acids. 

Jayasuriya H, Salituro GM, Smith SK, Heck JV, Gould SJ, Singh SB, Homnick CF, Holloway MK, Pitzenberger SM, Patane MA (1998) Complestatin to Chloropeptin I via a Quantitative Acid Catalyzed Rearrangement. Absolute Stereochemical Determination of Complestatin. Tetrahedron Lett 39 2247... 

Diels-Alder reaction of 2-bromoacrolein and cyclopentadiene using 10 mol% of titanium catalyst 74 gave the synthetically versatile (R)-bromoaldehyde adduct 75 in 94% yield, 67 1 exo. endo diastereoselectivity, and 93% ee. The absolute stereochemical outcome of the reaction is consistent with the proposed transition state assembly 76 in which the dienophile coordinates at the axial site of the metal, proximal to the indane moiety through Ji-attractive interactions. In this complex, the 7t-basic indole and the Ji-acidic dienophile can assume a parallel orientation facilitated by the octahedral geometry of the transition metal. The aldehyde would then react through a preferential s-cis conformation (Scheme 17.27).54... 

Chen, C., Chang, V., Cai, X., Duesler, E., and Mariano, P.S. (2001) A general strategy for absolute stereochemical control in enone-olefin [2 + 2] photocycloaddition reactions. Journal of the American Chemical Society, 123, 6433-6434. 

The same loss of absolute stereochemical information (but retention of relative stereochemistry) occurs in another reaction that you met at the start of this chapter. We then emphasized two features the acceleration in rate and the retention of stereochemistry. 

Standardized and consistent representations of stereoisomers and stereoisomeric mixtures are similarly important for the unique representations of distinct compounds. Recent file formats such as SDF v3000 and ChemAxon Extended SMILES provide clear definition and representation of complex relative and absolute stereochemical configurations. In practice these are not widely used because many commercially available files are represented by established v2000 or SMILES formats and also because HTS compounds are mostly relatively simple low molecular weight structures. 

This is mainly due to the fact that by means of chiral ligands it is comparatively facile to transfer absolute stereochemical information to a cat-alytically active metal center. However, the success of some of these reactions (e.g. the Sharpless asymmetric epoxidation or the Noyori hydrogenation) must not hide the fact that the number of powerful transition metal-catalyzed C-C coupling reactions, which proceed reliably with high enantioselectivity, is still rather small. 

Absolute stereochemical control has been observed in the ene reaction of the a-chloroni-troso carbohydrate derivative 2, although only in the case of 1-methylcyclohexene was it possible to determine the level of asymmetric induction (>4 1)35. 

A recent report details absolute stereochemical control at levels of up to 75 25 in ene reactions, although typical levels are lower35. This selenium reagent has two identical, chiral sulfur atoms and it is these stereogenic centers that provide for reagent-based control of absolute stereochemistry. 

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