A Carbohydrate Approach to the Enantioselective Synthesis of 1,3-Polyols

Abstract

Treatment of per-O-benzoyl-D-glycero-D-gulo-heptono-1,4-lactone (2) with tertiary amines afforded selectively and with good yields the (5H)-furan-2-one derivatives 3, 4, and 5, formed by controlled elimination of one, two, or three molecules of benzoic acid, respectively. The stereochemistry for the exocyclic double bonds of 4 and 5 was determined by means of NMR techniques. Particularly, the furanone 4 was obtained from 2 ( approximately 90% yield) as a mixture of the E and Z diastereoisomers, which were separated by column chromatography or, more efficiently, by HPLC. The catalytic hydrogenation of compounds 4-E and 4-Z took place diastereoselectively, due to the chiral induction of the stereocenter located in the lateral chain. Thus, hydrogenation of 4-E led to a mixture of the 4,5-dihydro-(3H)-furan-2-ones having 3R,5S,2'S (D-xylo, 6) and 3S,5R,2'S (D-arabino, 7) configurations, with 6 as the major product; whereas the 4-Z isomer gave the same mixture, but being 7 preponderant. On hydrogenation of the original 4-E/Z mixture, compound 6 was obtained pure after recrystallization. O-Debenzoylation of 6gave 9, which was reduced with NaBH(4) to the 3,5-dideoxy-meso-xylo-heptitol (11). The peracetate (12) and perbenzoate (13) of the latter were prepared, and the 1-(tert-butyldiphenylsilyl)oxy derivative (16) was also synthesized via the 3'-(silyloxy)-4,5-dihydro-(3H)-furan-2-one 14. Chemoselective reduction of the lactone function of 6 with diisoamylborane gave the 2,5,6-tri-O-benzoyl-3,6-dideoxy-D-xylo-heptofuranose (17). The 3,5-dideoxy-D-arabino-heptitol (18), a diastereoisomer of 11, was also isolated and characterized.

Enantioselective Synthesis of (2R,4S)- and (2S,4R)-4-Hydroxypipecolic Acid from d-Glucoheptono-1,4-lactone

“…The configuration of C-2 in 14 was established by 1 H NMR spectroscopy. As we have previously described , and in agreement with earlier studies on the elucidation of the geometry of 2,4-disubstituted butyrolactones 18 (4,5-dihydro-3,5-disubstituted-(3 H )-furan-2-ones), the large values for the coupling constants ( J ) between H-3,3‘ with H-2 and H-4 indicate a threo relationship for the substituents on C-2 and C-4. This situation is encountered in tosylate 13 ( J 2,3 = 8.4 Hz, J 2,3 ‘ = J 3 ‘ ,4 = 10.2 Hz, J 3,4 = 5.2 Hz), which bears a cis orientation for the ring substituents.…”

Synthesis of Optically Active 2-Alkoxy-2H-pyran-3(6H)-ones. Their Use as Dienophiles in Diels−Alder Cycloadditions

“…Carbohydrate-derived sugar enones have been employed for the synthesis of a variety of asymmetric molecules, and they constitute versatile building blocks for the construction of natural products . Due to the highly stereoselective nature of addition reactions to the enone system of these sugar derivatives, we have employed them for the enantioselective synthesis of natural products, in particular diamino tetradeoxy sugars found in antibiotics, and for the preparation of modified glycosides . Lichtenthaler and co-workers have described convenient procedures for the synthesis of 4-acyloxy-6-acyloxymethyl dihydropyranones (enolone esters) and their use as six-carbon synthons of non-carbohydrate natural products such as (−)-palythazine and (−)-bissetone .…”

The β-elimination route to stereodefined γ-alkylidenebutenolides

“…In a similar manner, the perbenzoate lk-21 of D-seduheptulonolactone and triethylamine undergo multiple b-eliminations (Scheme 7). [18][19][20] As in the case of Scheme 6, the second elimination lacks stereocontrol since the g-alkylidenebutenolide 23 forms as a 55+45 mixture of anti-elimination product Z-23 and syn-elimination product E-23. 19 By a 10-fold increase of the reaction time, a third elimination of benzoic acid ensued.…”

“…[18][19][20] As in the case of Scheme 6, the second elimination lacks stereocontrol since the g-alkylidenebutenolide 23 forms as a 55+45 mixture of anti-elimination product Z-23 and syn-elimination product E-23. 19 By a 10-fold increase of the reaction time, a third elimination of benzoic acid ensued. It 24 Reagents: i, HCl (12 M), CH 2 Cl 2 , MeOH, 78%; ii, same as (i), 73%; iii, same as (i), 65%; iv, same as (i), 71%; v, Bu t Me 2 SiCl, imidazole, molecular sieves 4 Å, DMF, 73%; vi, same as (v), 48%; vii, same as (v), 70%; viii, same as (v), 51%; ix, triflic anhydride, pyridine, CH 2 Cl 2 , 81% of a 99+1 Z-43+E-43 mixture; x, same as (ix), 69% of a 97+3 Z-44+E-44 mixture; xi, same as (ix), 63% of a 96+4 E-43+Z-43 mixture; xii, same as (ix), 73% of a 97+3 E-44+Z-44 mixture; xiii, HF•pyridine, THF, 96% of a 94+6 Z-45+E-45 mixture; xiv, same as (xiii), 92% of diastereopure Z-46; xv, same as (xiii), 86% of a 94+6 E-45+Z-45 mixture; xvi, same as (xiii), 96% of a 95+5 E-46+Z-46 mixture.…”