Glyceraldehyde acetonides

An allylcadmium reagent was reported to add to D-glyceraldehyde acetonide with high Cram selectivity and moderate regioselectivity58. 

Higher degrees of induced stereoselectivity emerge from the reactions of (/ )-glyceraldehyde acetonide with several enolates. For example, a single diastereomeric adduct results from the reaction of the acetonide with the lithium enolate of pinacolone4. 

Reactions of nitro compounds with chiral imines have only recently been described. Either chiral 1-phenylethylamine (auxiliary) or the glyceraldehyde acetonide aldehyde was used as the chiral precursors of the imines 66 and 68, which reacted with 3-mesyloxynitropropane to give the 3-nitropyrrolidines dl)-67 and 69, respectively, with good diastereoselectivity. In fact, both products were obtained (almost) exclusively as trans diastereomers with high level of asymmetric induction, but the configurations of the newly formed stereocenters were not determined [44] (Scheme 13). N-Boc imines can be formed... 

Optically pure glyceraldehyde acetonides are widely used in the synthesis of enantiomerically pure compounds (EPC synthesis).1 2 3 4 5 Whereas D-(R)-glyceraldehyde acetonide is easily obtained from the inexpensive D-mannitol,6 7 there are only a limited number of practical syntheses of the enantiomeric L-(S)-glyceraldehyde acetonide.8 9 Difficulties arise from different sources 1) availability of the starting material diisopropylidene-L-mannitol 2) length of the synthesis 10 3) nature of the reactants used mercury acetate, mercaptans, lead tetraacetate, ozone at -78°C, 4) moderate yields.11 14... 

GLC analysis of a sample of the crude, aqueous solution Indicates the presence of 95% of the theoretical amount of glyceraldehyde acetonide. This crude, aqueous solution can be used for further chemical transformations,2 but was not stored for more than 6 hr at 0°C. GLC analysis of the aqueous layer after dlchloromethane extraction still Indicates the presence of about 30% of the total amount of glyceraldehyde acetonide in the aqueous solution. 

S)-Glyceraldehyde acetonide is an unstable liquid that starts to polymerize... 

L-(S)-Glyceraldehyde acetonide 1,3-Dioxolane-4-carboxaldehyde, 2,2-dimethyl-, L- (8) 1,3-Dioxolane-4-carboxaldehyde, 2,2-dimethyl-, (S)- (9) (22323-80-4) Sodium (meta)periodate Periodic acid, sodium salt (8,9) (7790-28-5) 5,6-0-lsopropylidene-L-gulono-1,4-lactone L-Gulonic add, 5,6-0-(1-methylethylidene)-, y-lactone (11) (94697-68-4)... 

Dimethoxybenzylamine was purchased from Aldrich Chemical Company, Inc., and used without any purification. It is air sensitive and decomposes on standing into a white solid (3,4-dimethoxybenzoic acid). The success of the Cycloaddition depends on having stoichiometric quantities of reagents. The quantity of 3,4-dimethoxybenzylamine added (less than one equivalent) is related to the average quantity of glyceraldehyde acetonide present in the crude aqueous solution. 

DIASTEREOSELECTIVE HOMOLOGATION OF D-(R)-GLYCERALDEHYDE ACETONIDE USING 2-(TRlMETHYLSILYL)THI AZOLE 2-0-BENZYL-3,4-IS0PR0PYLIDENE-D-ERYTHR0SE (1,3-Dloxolane-4-acetaldehyde, 2,2-dimethyl-a-(phenylmethoxy)-, [R-(R, R )]-)... 

Figure 10. Reactions of allyl- and crotylboronates with D-glyceraldehyde acetonide (23).

Figure 13. Reaction of D-glyceraldehyde acetonide with tartrate allylboronate 36.

The increased enantioselectivity of 88 is also apparent in reactions with chiral aldehydes (Figure 28). p-Alkoxypropionaldehydes 90 were relatively poor substrates when 36 was used.3 The best selectivity ever obtained for syn diastereomer 91 in the matched double asymmetric reactions was 89 11 [(S,S)-36 and 90a], whereas the best selectivity for anti diastereomer 92 was 87 13 [reaction of 90b and (R,R)-36. In contrast, the allylborations of 90a,b with the new reagent 88 now proceed with up to 97 3 selectivity for either product diastereomer. Even more impressive results were obtained with glyceraldehyde acetonide (23) the matched double asymmetric reaction leading to 29 now proceeds with 300 1 diastereoselectivity, while the mismatched combination leading to 30 proceeds with 50 1 selectivity. 

Fluorofuranose precursors are prepared via Horner-Emmons reaction on L-glyceraldehyde acetonide (Figure 6.11). Due to the allylic position of the base, these compounds are much more unstable than the related saturated molecules (cf. Figure 3.17, Chapter 3). The presence of the fluorine atom enhances the hydrolytic stability of these compounds. Some of these molecules have good antiviral activities on infected cells. 

The reaction protocol was further extended to the concise synthesis of poly-oxamic acid, the unique polyhydroxyamino acid side-chain moiety of the antifungal polyoxin antibiotics (63). Treatment of the template 205 under standard thermal cycloaddition conditions with (5)-glyceraldehyde acetonide led to the formation of a single diastereoisomer 208 in 53% yield. Subsequent template removal released polyoxamic acid 209 in essentially quantitative yield. This represents a matched system, with the mismatched system leading to more complex reaction mixtures (Scheme 3.70). 

Adduct 33 has been exploited in the synthesis of the antiretroviral agent 34100 (equation 24), while ent-33, obtained from D-glyceraldehyde acetonide (ent-32), was converted into 35, a fluoro analogue of 2-deoxyribonolactone, a DNA lesion product101 (equation 25). 

A. Dondoni and P. Merino, Diastereoselective homologation of D-(ft)-glyceraldehyde acetonide using 2-(trimethylsilyl)thiazole 2-0-benzyl-3,4,-0-isopropylidene-D-erythrose, Org. Synth. 72 21 (1993) The procedure has been checked by A. I. Meyers and G. P. Brengel, Colorado State University, USA. 

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