Alcohols stereochemical inversion

CU4S4] species in which the TADDOL-derived ligand was an unexpected sul-fur-monodentate and not a S/X-bidentate ligand. This hypothesis was confirmed by NOE NMR spectroscopy that suggested a different structure for the Cu complex of the alcohol ligand relative to the methylether and the dimethylamino ligands, which could explain the observed stereochemical inversion. 

The systematic study of nucleophilic substitutions of steroid alcohols and halides, pursued by Shoppee since 1946 [47], has yielded many examples of reactions which proceed with stereochemical inversion (Walden Inversion) [48] at the reaction centre. Acetolysis of the epimeric 3-chloro-5a- [4 ] and 3-chloro-5/ -cholestanes [4g] with potassium acetate in acetic acid gives 3-acetoxy derivatives of inverted configurations (Fig. 14) cholestenes, derived by elimination reactions, are... 

By applying a similar approach, Wu and coworkers [135] observed a highly double-stereoselective hetero Diels-Alder addition between diene 245 and ethyl glyoxylate. This reaction was catalyzed by the (salen)Co° complex 246 (Scheme 13.75). The major adduct 247 is hydroborated to give alcohol 248. Stereochemical inversion is achieved via oxidation and subsequent reduction to 249. Acid methanolysis followed by diol protection furnishes 250. Quenching of the lithium enolate of 250 with phenyl disulfide and subsequent oxidation with A-bromosuccinimide forms, after deprotection, (-f)-KDO (3-deoxy-D-mann6>-oct-2-ulosonic acid) [136a]. 

Upon treatment with BFj OEt2, stannane 265 is isomerized via an inter-molecular pathway, resulting in allylic transposition and stereochemical inversion of configuration to yield 266 (Scheme 5.2.57, bottom), and this process provides an efficient route to non-racemic y-(alkoxy)allylic stannanes. The reaction of stannane 267 is advanced with unsaturated aldehydes and achieves facial selectivity by the antiS mechanism giving mainly the syn product 268, containing an E-alkenyl ether. The anti-SE arrangement shown in 270 minimizes non-bonded interactions leading to the major product. Similarly, the chiral stannane 271 adds to aliphatic aldehydes to produce the E-iyn-alcohol 272 (Scheme 5.2.58). ... 

The first way uses chemistry you have already met. When a nucleophile opens an epoxide, it generates an alcohol. If the nucleophile is water, the product is the diol. The epoxide opening in an 5 2 reaction goes with stereochemical inversion, so in this example the two hydroxyl groups end up on opposite sides of the six-membered ring the product is an anti diol. The epoxide opening reaction can be done in acid or in base. 

One of the most important reasons for using tosylates in S j2 reactions is stereochemical. The S]s]2 reaction of an alcohol via an alkyl halide proceeds with hvo inversions of configuration—one to make the halide from the alcohol and one to substitute the halide—and yields a product with the same stereochemistry as the starting alcohol. The SN2 reaction of an alcohol via a tosylate, however, proceeds with only one inversion and yields a product of opposite stereochemistry to the starting alcohol. Figure 17.5 shows a series of reactions on the R enantiomer of 2-octanol that illustrates these stereochemical relationships. 

The Mitsunobu reaction offers a powerful stereochemical transformation. This reaction is very efficient for inverting the configuration of chiral secondary alcohols since a clean SN2 process is generally observed ( Mitsunobu inversion ). Considering the fact that Mitsunobu chemistry is typically carried out at or below room temperature, high-temperature Mitsunobu reactions performed under microwave con-... 

The isomer (Z,Z)-319 furnished under identical conditions, surprisingly, the (15, 2Z,7Z)-cyclonona-2,7-dienyl carbamate 323 with 88% ee, which could be converted to the free alcohol 324 (equation 86). The stereochemical outcome implies inversion of the configuration at the carbanionic centre in (S)-322. The method could also be successfully applied to 5-oxy-substituted dienes. ... 

Usually, to homologate an alcohol such as 1 to the corresponding nitrile 2 one would expect to first convert the alcohol into a leaving group. Nasser Iranpoor and Habib Firouzabadi of Shiraz University, Iran, have shown (J. Org. Chem. 2004, 69, 2562) that on exposure to a combination of Ph,P, Bu NCN and DDQ, 1 is converted directly to 2. The stereochemical outcome was not mentioned, but one would expect the reaction to proceed with net inversion, as illustrated. 

Scheme 6.11 Stereochemical course (retention versus inversion) for the synthesis of oxazolidin-2-ones from amino alcohol derivatives and C02 using DBU as the base and n-Bu3P/ DBAD as Mitsunobu s reactants, in CH3CN.

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