1.1- Diols hemiketals

Accordingly, 14 was converted under standard dihydroxylation conditions to hemiketal 45 in 80% yield. Selective benzylation of 45 provided benzyl ether 46, which was transformed to the diketone 47, over two steps ketone reduction, and subsequent reoxidation of the resultant diol. Treatment of 47 under our standard reductive amination conditions (1.2 equivalents NH4HCO2, NaCNBH3, dry MeOH, 4A MS, 2h) provided the aza-p-C-galactoside 12 in 72% yield. The structure of 12 was confirmed by HCOSY, 13CNMR and MS analysis. No diastereomeric products were observed within the limits of NMR detection (Scheme 7). 

A pronounced difference in reactivity between fluorinatcd and nonfluorinated compounds is observed when diols (e. g., 13) react with an oxo compound. Under acidic conditions condensation with acetone with 13 yields the dioxolanc. Without further activation, hexafluoroaceione reacts with 13 to give a hemiketal that readily reacts with diazomethane, and the monohydroxy compound 14 is isolated. 

Hvoslef suggests that the hemiketal form of DHA is converted slowly to the open side-chain form in water. Ward (33) shows that the presumed open side-chain form is actually DKG, which has NMR shifts as shown in Table III. In the NMR spectra of DKG the shifts of C2 and C3 are characteristic of gem-diols and thus the principal form of DKG in aqueous solution is with fully hydrated carbonyls on C2 and C3. 

A novel one-pot Dess-Martin oxidation was developed for the construction of the y-hydroxy lactone moiety of the CP-molecules in the laboratory of K.C. Nicolaou. Bicyclic 1,4-diol was treated with 10 equivalents of DMP in dichloromethane for 16h to promote a tandem reaction first, the bridgehead secondary alcohol was selectively oxidized to the ketone, followed by a ring closure to afford the isolable hemiketal, which was further oxidized by DMP to give a keto aldehyde. Trace amounts of water terminated the cascade to give a stable diol, which was not further oxidized with DMP. Subsequent TEMPO oxidation furnished the desired y-hydroxy lactone. 

When this reaction is conducted on ketones, instead of aldehydes, the equivalent species to the hemiacetal and acetal are now called hemiketal and ketal respectively. However, when simple ketones are reacted with normal monofunctional alcohols, the reaction rarely goes to completion, unlike the situation with aldehydes where the reaction proceeds smoothly. Yet, when a 1,2-diol is reacted with a ketone, then the reaction goes to completion much more readily. Write the complete reaction sequence for the formation of the cyclic ketal starting from propanone and 1,2-ethandiol, under acidic conditions. Also, suggest why the product between one molecule of each reagent is favoured over the alternative product that would result from the reaction between two molecules of the diol and one of the ketone. 

Thermal decomposition of diethyl 1-ethoxycarbonyl-l-diazomethylphosphonate catalyzed by Rh2(OAc)4 in the presence of propylene oxide gives diethyl 1 -ethoxycarbonyl- 1-oxomethyIphos-phonate.5 Although stable under anhydrous conditions, this compound hydrates quantitatively in H2O, giving the gem-diol, whereas MeOH adds quantitatively to form the hemiketal. ... 

In this reaction they form hemiketals with the serine present at the active site of the enzyme two possible reaction mechanisms are enzyme addition to the carbonyl (30) or condensation with the geminal diol (31) (enhanced by the hydrophobic aliphatic chain in the molecule) (Equation 3). 

Another synthetic strategy for partially or completely inhibiting intramolecular cyclization of erythromycin to hemiketal (8) and spiroketal (9) is modification of the functional groups that participate in the cyclization reactions. These groups include the C-9 ketone, C-6 hydroxyl, and C-8 proton in addition to the 11,12-diol discussed above. These approaches have led to a variety of semi-synthetic derivatives of erythromycin, some of which have been recently approved by regulatory agencies or are in late stages of clinical trials [12-17],... 

The unique oxidizing properties of DMP are best illustrated by its numerous applications in the total synthesis of the CP-molecules, lead structures for cardiovascular and anticancer drugs, published by Nicolaou and coworkers in 2002 [1273-1275]. For example, in the course of this synthetic study, a hindered secondary alcohol 884 was oxidized with DMP to give stable diol 886 via intermediate formation of hemiketal 885 (Scheme 3.356) [1274]. 

Alcohols add reversibly to aldehydes and ketones to give a transient hemiacetal or hemiketal, which then reacts with more alcohol to give an acetal or a ketal. Acetal and ketal formation is reversible. An excess of alcohol drives the reaction toward the acetal or ketal, but an excess of water will convert the acetal or ketal back to the aldehyde or ketone. 1,2-Diols react with aldehydes and ketones to give 1,3-dioxolane derivatives and 1,3-diols react to give 1,3-dioxane derivatives. 

The formation of hemiketals and ketals from alcohols and ketones is exactly analogous (with somewhat more difficulty as ketones are generally less reactive than aldehydes Chapter 9). In the reaction of a ketone, such as cyclohexanone (Table 8.6, item 12) with a 1,2-diol, such as 1,2-dihydroxyethane (ethylene glycol [HOCH2CH2OH]) (Scheme 8.52), the second equivalent of alcohol is part of the initial alcohol substrate and the cyclic product results. 

TTie first item in Table 9.3 is simply the familiar hydration (see, e.g., Rgure 8.4) of aldehydes and ketones. As previously discussed, these geminal diols are normally in equilibrium with the corresponding carbonyl (C=0) compound and, with few exceptions (e.g., methanal [formaldehyde, H2CO] 2,2,2-trichloroacetaldehyde [chloral, CI3CCHO], see Chapter 8), the equilibrium lies far on the side of the aldehyde or ketone. The same general ideas obtain with regard to the next three items in Table 9.3, except that hemiacetals and hemiketals in cyclic systems (e.g., carbohydrates, Chapter 11), are more common than their open chain forms. 

Pimpifolidine (hemiketal) 22,26-Epimino- 16P.23-epoxy-5a,22ot//, 25aff-cholestan-3P3 -diol, Fig, 7.23 (deriv.) S. pimpinellifolium JussL. sub nom. L. pimpinellifolium (JussL.) Mill. (3)... 

Reaction is acid catalyzed and proceeds by way of a hemiacetal or hemiketal as an intermediate. Equilibrium constant normally favorable for aldehydes, unfavorable for ketones. Cyclic acetals from vicinal diols form readily. 

Thus, far, Kdo phosphite glycosyl donors have found only very limited interest The dihenzylphosphite Kdo donor 172 had heen prepared hy Ichiyanagi et al. by reaction of the hemiketal 42 with diben l N,N-diisopropylphosphoramidite and l//-tetrazole in 56% yield. Subsequent glycosylation reactions with diol 47, to produce disaccharide 48, were catalyzed either by TMSOTf or equimolar BF3 Et20 but gave poor yields and anomeric selectivities (Scheme 26). 

An abnormal unidirectional Claisen reaction has been reported for the addition of deprotonated cyclohexyl [l- C]acetate (58) to the carbonyl group of the a-N-Boc-substituted lactone 59, providing hemiketal 60 (Figure 6.24). The competitive condensation of the enolate anion of 59 with 58 is probably hindered for steric reasons by the deprotonated A-Boc group or because of its negative charge. Subsequent catalytic reduction furnished a mixture of the A-Boc-amino diol 61 and its epimer. Deprotection of the desired epimer followed by base-catalyzed cyclization provided lactam 62, the key intermediate in the synthesis of [3- C]castanospermine 63. ... 

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