Carbonyl diol activation

An alternative strategy for promoting Diels-Alder reaction by proton involves the activation of dienophile by hydrogen bonding [93]. Biphenylene diol 143 (Scheme 4.26) forms doubly hydrogen-bonded complexes with a,j]-unsaturated carbonyl compounds, which strongly accelerate the Diels-Alder... 

Another well-known transformation of carbonyl derivatives is their conversion to pinacols (1,2-diols) via an initial one-electron reduction with highly active metals (such as sodium, magnesium, aluminum, samarium iodide, cerium(III)/ I2, yttrium, low-valent titanium reagents (McMurry coupling), etc.), amines, and electron-rich olefins and aromatics as one-electron donors (D).43 Ketyl formation is rapidly followed by dimerization44 (equation 22). 

The enantioselective hetero-Diels-Alder (HDA) reaction of carbonyl compounds with 1,3-dienes represents an elegant access to optically active six-membered oxo-heterocycles. Since the pioneering work of Rawal et al. in 2003 [55], the enantioselective HDA reaction catalyzed by diols (such as TADDOLs) has become a flourishing field of research [56]. 

Tetrahydrofuran itself can be opened using either the stoichiometric or the catalytic version of arene-promoted lithiation, but both cases need the activation by boron trifluoride. The catalytic reaction was performed by treating the solvent THF 324 with the complex boron trifluoride-etherate and a catalytic amount (4%) of naphthalene. The intermediate 325 was formed. Further reaction with carbonyl compounds and flnal hydrolysis yielded the expected 1,5-diols 326 (Scheme 95), which could be easily cyclized to the corresponding substituted tetrahydropyrans under acidic conditions (concentrated FlCl). 

Both unsymmetrical diols and alkenes can be prepared by applying these methods to mixtures of two different carbonyl compounds. An excess of one component can be used to achieve a high conversion of the more valuable reactant. A mixed reductive deoxygenation using TiCl4/Zn has been used to prepare 4-hydroxytamoxifen, the active antiestrogenic metabolite of tamoxifen. 

In the reaction of ethyl 2,4-difluoro-3-oxobutanoate (18) with potassium borohydride the carbonyl group is reduced and, in parallel, the most activated a-C-F bond is hydrogenolyzed to give ethyl 4-fluoro-3-hydroxybutanote (19).124 At higher temperatures the diol 20 is formed. 

The oxidation of 1,4- and 1,5-diols with many oxidants leads to intermediate hydroxycarbonyl compounds that equilibrate with lactols, which are transformed in situ into lactones. This side reaction is very uncommon during Swern oxidations, due to the sequential nature of alcohol activation versus base-induced transformation of the activated alcohol into a carbonyl compound. Thus, during the oxidation of a diol, normally when the first alcohol is transformed into an aldehyde or ketone, the second alcohol is already protected by activation, resulting in the impossibility of formation of a lactol that could lead to a lactone. 

During selective oxidations of 1,4- and 1,5-diols with active Mn02, sometimes the unreacting alcohol forms a lactol by interaction with the carbonyl group resulting from the oxidation of an unsaturated alcohol. This lactol can be further oxidized to a lactone.70... 

The catalytic performance of Nafion SAC-13 in the formation of 1,1-diacetates,677 in turn, is very similar to that of HBF4-silica. In the acetalization of carbonyl compounds with ethane-1,2-diol and propane-1,3-diol, products are isolated in good to excellent yields. The formation of THP ethers of alcohols is fast and protected alcohols are isolated in high yields [Eq. (5.238)]. Nafion SAC-13 can also be used in the removal of the THP ether group677 although the transformation requires somewhat longer reaction times (30 min-6 h, 81-97% yield). Furthermore, the catalyst could be recycled in all three processes with practically no loss of activity. 

Allyl boronates react very slowly with carbonyl compounds as compared to the corresponding allyldialkylboranes, due to the presence of two oxygen atoms on boron which diminish the Lewis acidity of boron. However, the activity of the allyl boronates can be enhanced by the addition of Lewis acid catalysts. There have been two complementary approaches described for the stereoselective allylation with allyl boronates, one involving the use of chiral Lewis acid, and the other involving chiral allyl boronates in conjunction with achiral Lewis acid catalyst. Several chiral fVsymmetric-based 1,2-diols 197 have been employed in combination with SnCLj as a Lewis acid and excellent level of enantioselectivity has been observed for the allylation to furnish homoallylic alcohols 198 with high ee (Equation 8) <2006AGE2426>. 

The hydroxy group in the a-position to a carbonyl group is a common feature of many natural and biologically active compounds. Furthermore, this functionality is an obvious precursor in the synthesis of other important building blocks such as diols. 

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