Formal Synthesis of d-myo-Inositol 1,4,5-Tris(dihydrogen phosphate):  Cyclization by an Unusual Ene Reaction and Use of the Bu₂SnCl₂/Bu₂SnH₂ Reagent for Generating an Equatorial Alcohol

Abstract

D-Glucose was converted into the propargyl silane aldehyde 5, which, on treatment with camphorsulfonic acid, cyclized with retention of silicon. The allenic product (7) was elaborated via ketone 24 into 4, which had previously been converted into D-myo-inositol 1,4,5-tris(dihydrogen phosphate). Selective reduction of the advanced intermediate 24 was accomplished with Bu 2 SnCl 2 / Bu 2 SnH 2 , a reagent mixture that shows a very strong preference for generating equatorial alcohols. The cyclization step leading to allene 7 was studied by examining a number of model compounds; the unusual retention of silicon appears to be limited to highly oxygenated substrates, such as 5 and its all-benzyl analogue (27).

Stereoselectivity of Radical Reactions: Cyclic Systems

“…A related example has been reported by Clive during the synthesis of D-myo-inositol derivatives (Scheme 12, Eq. 12.2) [32]. Reduction of a polyoxygenated cyclohexanone derivative with CIBuZSnH was the only method to give exclusively the equatorial alcohol presumably via the pyramidalized ketyl radical 13.…”

Probing myo-inositol 1-phosphate synthase with multisubstrate adducts

“…17 The remaining free hydroxyl groups were then benzylated giving allyl-2,3,4-tri- O -benzyl-6- O -trityl-D-glucopyranoside ( 3 ) in excellent 92% yields. 18 After the removal of the allyl group, the reduction of the pyranose ring yielded 2,3,4-tri- O -benzyl-6- O -trityl-D-glucytol ( 4 ) almost quantitatively. tert -Butyldiphenylsilyl chloride was used to selectively protect the primary alcohol in 84% yields and the propargylation of the secondary alcohol at the C5 position was achieved in 72% yield by using propargyl bromide and sodium hydride in THF at reflux.…”

“…1 H (500 MHz CDCl 3 ) δ 7.71 (1H, s, H triazole), 7.44-7.42 (6H, m, H Ar ), 7.28-7.11 (42H, m, H Ar ), 6.93-6.92 (2H, m, H Ar ), 5.05 (1H, d, J = 3.8 Hz, H1′), 5.78 (1H, dd, J = 3.8 Hz, 5,2 Hz, H2′), 5.66 (1H, t, J = 5.2 Hz, H3′), 5.00-4.91(8H, m, CH 2 -OP), 4.78 (1H, d, J = 11.9 Hz, CH 2 -triazole), 4.63-4.40 (8H, m, CH 2 -Ph, H4′, CH 2triazole), 4.33-4.29 (1H, m, H1), 4.22-4.10 (3H, m, H1, H5′), 3.98-3.96 (1H, m, H3), 3.90-3.87 (1H, m, H5), 3.86-3.81 (2H, m, H4, H2), 3.60 (1H, dd, J = 2,7 Hz, 10.5 Hz H6), 3.32 (1H, dd, J = 5.2 Hz, 10.5 Hz H6), 2.09 (3H, s, CH 3 ), 2.06 (3H, s, CH 3 ). 13 (18). Using procedure B, (9) (0.043 g, 0.043 mmol) was mixed with (11) (0.023 g, 0.047 mmol) in a water-tBuOH (1 mL) mixture.…”

A Stereodivergent Approach to 5a‐Carba‐α‐D‐gluco‐, ‐α‐D‐galacto and ‐β‐L‐gulopyranose Pentaacetates from D‐Mannose, Based on 6‐exo‐dig Radical Cyclization and Barton−McCombie Radical Deoxygenation

“…Unfortunately, under the standard reaction conditions the starting material was recovered unchanged, thus reinforcing the hypothesis of the intermolecular hydride transfer for the reduction of the carbonyl group in 29 . Other attempts were carried out with the reagent system Bu 2 SnCl 2 /Bu 2 SnH 2 , introduced by Clive et al45 for the reduction of highly functionalized cyclohexanones with stereoselectivity opposed to that of conventional reagents. In our case, however, the starting material was recovered unchanged.…”