Regioselective eliminations in reactions of carbohydrate derivatives with superoxide, or with borohydride in 2-propanol

Abstract

Thispaper is dedicated to Prof. Raymond U . Lemieux on the occasion of his 60th birthday VANGA S. RAo and ARTHUR S. PERLIN. Can. J. Chem. 59,333 (1981).The reaction between 2,3,4,6-tetra-0-benzyl-1,5-di-O-mesyl-~-glucitol(2) and potassium superoxide resulted in the loss of H-4 and the 5-mesyloxy (as well as 1-mesyloxy) substituent, and an almost quantitative conversion into en01 ether 4, i.e., 1,3,4,5-tetra-O-benzyl-3-dehydro-2-deoxy-~-threo-hex-2-enitol. When the reaction was performed with 8, in which the 1-0-mesyl group (of 2) is replaced by 0-(methoxy)trityl, the outcome was wholly different: an olefin was formed through the removal of a primary (H-6) rather than a secondary (H-4) proton, and nucleophilic displacement also took place. Results similar to those for 8 were obtained with the 2-epimer of 2, i.e., 2,3,4,6-tetra-O-benzyl-1,5-di-O-mesyl-~-rnannitol (12). It is suggested that selective displacement of the 1-0-mesyl group of 2 by superoxide generates a 1-peroxy anion (6) that abstracts H-4 intramolecularly, promoting concomitant loss of the 5-mesyloxy group. The transition state for proton abstraction within anion 6 appears to be more stable than that of the corresponding anion in the manno series, accounting for the different reaction routes for 2 and 12. Elimination occurred also in the reduction of 2,3,4,6-tetra-0-benzyl-D-glucopyranose with sodium borohydride in 2-propanol, en route to 2, affording 2,4,6-tri-0-benzyl-2-dehydro-3-deoxy-~-threo-hex-2-enitol (21). The 'H nmr spectra of alditol derivatives 2, 8, and 12 show that these molecules depart substantially from extended zigzag conformations, in contrast to configurationally related peracetylated acyclic derivatives. 1,3,4,5 dehydro-3 deoxy-2 L-thrio-hexbne-2 itol. Si I'on effectue la meme reaction sur le compose 8qui correspond au remplacement du groupe 0-mesyl-1 (de 2) par un groupe 0-(methoxy)trityl, la reaction est tres differente. I1 se forme une olefine par I'intermediaire d'une elimination de I'hydrogeneprirnaire (H-6) plutBt que parcelle du proton (H-4) et il se produit ainsi un deplacement nucleophile. IAvec I'Cpimkre du compose 2, soit le tetra-0-benzyl-2,3,4,6 di-0-m6syl-1,5 D-mannitol (l2), on obtient des resultats semblables a I ceux que donne le compose 8. On suggere que le d6placement selectif du groupe 0-mesyl-1 du compos6 2 par le superoxyde, engendre un anion peroxy (6) qui enleve intramoleculairement H-4 en favorisant la perte concomitante du groupe mesyloxy en position 5. L'etat de transition lors de l'elimination du proton dans I'anion (6) semble itre plus stable que celui derivant de I'anion correspondant des series manno; ceci explique les reactions differentes de 2 et 12. Lors de la reduction du tetra-0-benzyl-2,3,4,6 D-gl~copyI'ano~e par le borohydrure de sodium dans le propanol-2, il se produit egalement une elimination qui conduit au tri-0-benzyl-2,4,6dChydro-2deoxy-3 D-thrio-hexene-2 it01 (21) plutBt qu'au compose 2 attendu. Les spectres rmn du 'H des derives alditol2,8, et 12 indiquent que ces molCcules s'eloignen...

New Access to Unsaturated Keto Carba Sugars (Gabosines) Using an Intramolecular Nozaki−Kishi Reaction as the Key Step

“…Starting from tetra- O -benzyl- d -glucose 2 , the silylated d -glucitol 8 was prepared, upon sodium borohydride reduction followed by silylation (Scheme ). Oxidation of 8 with either PCC in the presence of AcONa or with the Dess−Martin periodinane (DMP) gave the l -sorbose derivative 9 (90%).…”

Boron enolates in stereoselective syntheses of 2-enitols from O-benzyl aldoses by reaction with borohydride in 2-propanol. Configuration of E and Z enols from proton relaxation rates

“…Consequently, aside from the need for a strong base, it appeared that the borohydride was required, perhaps incorporated into a transient complex, to induce the selective production of 3. Therefore, instead of adding the borohydride to the solution of 1, as done originally, the aldose was added to a cold solution prepared previously by heating sodium borohydride under reflux in 2-propanol for 24 h. In this way, 1 was exposed from the outset to a strongly basic medium, as well as to an equilibrated mixture of alkoxyborohydrides from which the hypothetical boron complex could be generated. Under these circumstances, the yield of enediol 3 (isolated as diacetate 5) was increased from 50% to almost 100%.…”

“…1.5-Di-O -acetyl-2,4,6-tri-O -benzyl-2-dehydro-3-deoxy-Derytbro-hex-2(Z)-enitol (5). A suspension of sodium borohydride (1.0 g) in 2-propanol (lO mL), protected from moisture, was heated under reflux for 24 h and cooled to 5 °C, and 2.3.4.6tetra-O-benzyl-D-glucopyranose (1) (1.0 g) was introduced in one portion. The suspension was stirred at room temperature for 60 h and evaporated almost to dryness, water (60 mL) was introduced, followed by chloroform (50 mL), and the chloroform layer was washed successively with cold 5% hydrochloric acid, saturated sodium hydrogen carbonate, and water, dried (anhydrous sodium sulfate), and evaporated.…”

Synthesis of cycloprop[c]indol-5-ones from 4-diazo-3-[n-(2-propenyl)amido]cyclohexadien-1-ones. Exploration of copper(I) and copper(II) complexes as catalysts

“…Recrystallization from ethyl acetate/ether yielded 3.0 g (54%) of 12a: mp 165-167 °C; NMR (CDC13) 1.69 (s, 3 ), 2.17 (d, J = 0.9 Hz, 3 H), 3.64 (dd, J = 14.7, 7.5 Hz, 1 H), 4.52 (dd, J = 14. 6,5.7 Hz, 1 H), 4.84-4.92 (m, 2 ), 5.05 (dd, J = 17.9,12.1 Hz, 2 H), 5.55-5.67 (m, 1 ), 6.30 (s, 1 ), 7.07-7.12 (m, 2 ), 7.30-7.44 (m, 5 H), 7.56 (t, J = 7.4 Hz, 1 ), 7.71 (d, J = 7.6 Hz, 2 ), 7.81 (s, 1H). Homonuclear NOE irradiation of the C-3 methyl protons ( 2.17) resulted in a 17% enhancement in the Hc-2 signal at A pure sample of 12b was isolated from a reaction in which 12a and 12b were treated with BBr3.…”

“…The combined organic layers were dried (MgS04) and evaporated and the residue purified by flash column chromatography to yield 6.3 mg (54%) of 17. A spot that comigrated with a TLC standard of 2 was observed but could not be isolated on this small scale: *H NMR (DMSO) ó 2.14 (s, 3 H), 2.84 (s, 3 H), 3.38 (dd, «7 = 8, 10Hz, 1 H), 3.58 (dd,«7= 11,4 Hz, 1 H), 3.68 (m, 1 H), 3.85 (dd, «7= 11, 5 Hz, 1 ), 4.02 (dd, «7 = 10, 8 Hz, 1 ), 7.02 (s, 1 H), 7.73 (s, 1 ), 8.06 (s, 1 H). When 17 was treated with sodium hydride (2 equiv) in THF at 0 °C, it was cyclized to 2 in 90% yield.…”