Alkenes hydroxy group effect

Bis [(trifluoromethyl)thio] acetaldehyde (83a) has been prepared from an enam-ine precursor (84), although refluxing in aqueous ethanolic HCl is required to effect this reaction.The aldehyde is less stable than its enol tautomer (83b), and many reactions typical of aldehydes fail. For example, addition of aqueous silver nitrate immediately yields the silver salt of (83b), rather than giving precipitation of (elemental) silver. The (trifluoromethyl)thio substituent has pseudohalogenic character and, together with the hydroxy group, stabilizes the alkene tautomer in the manner of a push-pull alkene. The enol-aldehyde equilibrium mixture in acetonitrile shows an apparent of 2.6 when titrated with aqueous hydroxide. 

CEJ1358> and the ruthenium mediated isomerization of double bonds (cf. Scheme 89, Section 8.11.7) <2007TL137> are recent examples of transition metal catalyzed manipulations at the side chain carbon atoms of 1,3-heterocycles. A novel side-chain addition reaction of aldehydes to 6-alkylidene-l,3-dioxin-4-ones was used for the construction of intermediates of lophotoxin <2006CJC1226>. An acid-catalyzed intramolecular cycloaddition of a hydroxy group to an alkene has been effected by the presence of an adjacent 1,3-dithiane moiety <2006TL4549>. 

Thus good yields of p-alkoxy alcdiols can be obtained, albeit as diastereomeric mixtures, but unfortunately hydtoxymercurated alkenes unda similar conditions do not lead to useful products. Despite this iqrparent limitation, alkoxymercuration-oxidative demercuration has been very effective in a number of systems described below, and there is no doubt it is a procedure worth consi ration for hydroxy group introduction. 

The reaction is effective with electron-rich carbonyls such as trimethylsilyl esters and thioesters, as Table 20 indicates. Lactones are substrates for alkylidenation however, hydroxy ketones are formed as side products, and yields are lower than with alkyl esters. - Amides are also effective, but form the ( )-isomer predominantly. This method has been applied to the synthesis of precursors to spiroacetals (4W) by Kocienski (equation 115). The reaction was found to be compatible with THP-protected hydroxy groups, aromatic and branched substituents, and alkene functionality, although complex substitution leads to varying rates of reaction for alkylidenation. Kocienski and cowoikers found the intramolecular reaction to be problematic. As with the CrCb chemistry, this reaction cannot be used with a disubstituted dibromoalkane to form the tetrasubstituted enol ether. Attempts were nuide to apply this reaction to alkene formation by reaction with aldehydes and ketones, but unfortunately the (Z) ( )-ratio of the alkenes formed is virtually 1 1. ... 

Another often used chiral ligand is l,F-binaphthyl-2,2 -diyl-bis(phosphine), or binap.It can be built into ruthenium catalysts, which display high activities and enantio-selectivities for the hydrogenation of alkenes, amines, allylalcohols, and unsaturated carbonyls. A directing effect is observed for an a-hydroxy group in these cases. 

Fig. 1 Effect of the nature of the substituent group and of the substitution degree of the cyclodextrin on 2-ketone yields. The value in bracket indicates the number of functionalized hydroxy group. PdS04 (0.86 mmol), CuS04 (10 mmol), H9PV6Mo6O40 (10 mmol), DMCD (1 mmol), water (30 ml ), 1-alkene (40 mmol), 6 hours, T 80°C, P02 1 bar.

The Simmons-Smith reaction is influenced by a suitably situated hydroxy group in the alkene substrate. With allylic and homoallylic alcohols or ethers, the rate of the reaction is greatly increased and, in five- and six-membered cyclic allylic alcohols, the product in which the cyclopropane ring is cis to the hydroxy group is formed stereoselectively (4.89). These effects are ascribed to co-ordination of the oxygen atom to the zinc, followed by transfer of methylene to the same face of the adjacent double bond. 

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