1.3- diol acetonide

D.A. Evans, D.L. Rieger, J.R. Gage, NMR chemical shift correlations in 1,3-diol acetonides. Implications for the stereochemical assignment of propionate-derived polyols. Tetrahedron Lett. 31 (1990) 7099. 

Rychnovsky, S.D., and D.J. Skautzky Stereochemistry of Alternating Polyol Chains NMR Analysis of 1,3-Diol Acetonides. Tetrahedron, 31, 945 (1990). 

Analysis of literature NMR data for hundreds of 1,3-diol acetonides have proven this method reliable. Only a few types of substituents (fi and/or are problematic. The chemical shift correlations shown in Figure 8.27 only become unreliable when the substituents in the 4 and/or 6 position of the dioxolane ring are an 5p-hybridized carbon (alkyne or nitrile). Use of the acetal carbon chemical shift correlation is not quite as reliable, but of the hundreds of acetonides examined, fewer than 10% of iyn-l,3-diol acetonides and 5% of antt-l,3-diol acetonides would be misassigned based on the chemical shift of the acetal carbon alone—and practially none will be misassigned if the acetal chemical shift is considered in conjunction with the acetonide methyl chemical shifts. The only... 

FIGURE 8.27 NMR chemical shift correlations for 1,3-diol acetonides. (From Rychnovsky, S. D., B. N. Rogers, and T. I. Richardson, Accounts of Chemical Research 31 (1998) 9-17.)... 

Polyfunctional fluoronitro alcohois are provided by tlie SRNl reaction of a perfluoroalkyl iodide or alkylene diiodides with the anhydrous lithium salt of 2-nitropropane l,3-diol acetonide. Hydrolysis of the resulting perfluoroalkyl-... 

The syn-l,3-diol acetonide is ultimately established by reductive decyanation. These reactions proceed with exceptionally high selectivity. The selectivity observed in reductive decyanations could in principle have two origins ... 

A recently developed method for acyclic 1,3-diols rests on acetonide formation and 13C-NMR spectroscopic investigation of the acetonides. The conformational difference between the syn (chair) and anti (twist) diol acetonides results in significantly different 13C chemical shifts of the acetone derived carbons25°. This is a highly useful method in the context of the synthesis of polypropanoate-derived natural products260. 

Reductive decyanation. This reaction is a key step in a route to syn-l,3-diol acetonides from P-trimethylsilyloxy aldehydes (1). Reaction of 1 with trimethylsilyl cyanide followed by acetonation gives a 1 1 mixture of a protected cyanohydrin (2). This mixture is converted into a single isomer (3) on alkylation of the anion of the cyanohydrin acetonide. Reductive decyanation with Na-NH3 at -78° produces a syn-diol acetonide (4). The apparent retention of configuration in the reduction results from preferential formation of an intermediate axial anion. 

Compounds 80 and 93 were reisolated by Sawa and his cowoikers from C. cordata along with a new biaryl type macrocyclic diarylheptanoid (84) containing an unusual diol acetonide function. 

Rychnovsky has employed highly stereoselective reductive decyanations of cyanohydrin acetonides in the synthesis of vy -l,3-diols [9, 10]. In the reduction of a 52 48 mixture of cyanohydrin acetonides by lithium in ammonia at —78°C, the stereochemistry of the reduction is set during the rapid and non-selective electron transfer to the intermediate axial radical, which generates the configurationally stable axial alkyllithium. Subsequent protonation from the axial direction gives the yy -l,3-diol acetonide with >100 1 stereoselectivity (Scheme 4). The same syn-... 

An alkylation/reductive decyanation method was developed for the efficient synthesis of xjn-l,3-diols [9, 10]. Cyanohydrin acetonides are rapidly deprotonated by amide bases and alkylated with suitably reactive electrophiles to yield diaste-reomerically pure coupled products. Subsequent exposure to Li/NHa affords exclusively xy -l,3-diol acetonides (see above). Although the alkylation itself is stereoselective, it is noteworthy that the, 2>-syn stereochemistry is ultimately set in the reductive decyanation by virtue of the anomeric axial radical intermediate. This methodology was effectively applied in the total synthesis of the polyene macrolide roflamycoin (Scheme 15) [23]. Noteworthy is the formation of the entire protected polyol segment of roflamycoin by treatment of a late-stage intermediate with Li/ NHa to effect a simultaneous decyanation/debenzylation. 

OH/Br exchange (aq. HBr/PBr3), 303 porphyrin synthesis with, 255, 349 Hydrobromination of alkynes with Zr, 132, 325 Hydrochlorothiazide, 310 Hydrofluoric acid aq. HF) deblocking with of diol acetonides, 277 of silyl ethers, 277, 329 of silyl thioethers, 169 Hydroformylation of alkenes, 46-48 Hydrogenation, 96-105 See also Hydrogenolysis) of alkenes, 41, 96-97, 101-103, 278, 283 of alkynes to (Z)-alkenes, 40, 64,100-101... 

Scheme 4, Conversion ofbromobenzene into a trimethylsilyl cyclohexadiene-1,2-cis-diol acetonide.

Figure 2. Diels-Alder cycloadduct dimers of dimethylphenylsilane cis-diol acetonide (5a) and dimethylvinylphenylsilane cis-diol acetonide (5b). 

Epoxidation of a cn>diol acetonide bearing a hydrosilane functionality... 

Rychnovsky SD, Zeller S, Skalitzky DJ, Griesgraber G. Stereoselective synthesis of syn-l,3-diol acetonides by reductive decyanation of cyanohydrins. J. Org. Chem. 1990 55 5550-5551. 

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