Conformational properties of 5-alkoxy and 5-alkyl substituted trimethylene phosphates in solution

Gerlt, J.A.; Gutterson, Neal; Drews, Reed E.

doi:10.1021/ja00525a035

Cited by 14 publications

(5 citation statements)

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“…Empirical approximations to estimate the population and the Δ G ° for the chair/nonchair equilibria in solution are known, but most are method dependent. ,6a, Based on the very good matching between the X-ray structures and the calculated structures of phosphate 16 , we can establish the relative energies and free energies for conformer pairs 16c / 16b and 15c / 15b ( G = H − TS, as the “sums of the electronic and thermal free energies”, obtained at T = 298.15 K) . For the equilibrium 16c / 16b , Δ E ° rel = +0.78 kcal/mol and the G = +1.27 kcal/mol, leading to an approximate population of 56% and 44% for the chair and boat conformations, respectively, and for the equilibrium 15c / 15b , Δ E ° rel = +1.21 kcal/mol, G = +0.69 kcal/mol, 79% and 21% of 15c and 15b , respectively.…”

Section: Resultsmentioning

confidence: 99%

Intramolecular Hydrogen Bonding (PO--H) Stabilizes the Chair Conformation of Six-Membered Ring Phosphates

et al. 2005

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[reaction: see text] Six-membered cyclic phosphates (2-phenoxy-2-oxo-1,3,2-dioxaphosphorinanes) bearing an internal protected or unprotected hydroxyl group were designed, synthesized, and studied by NMR and computational methods. Selective opening of O-isopropylidene-protected 1,2-diols at the primary site was achieved with either triethylsilane or trimethylallylsilane in the presence of BF3.OEt2. Applied to 5,6-O-isopropylidenepentofuranosides, this reaction gave rise to the formation of the corresponding 1,3-diol precursors for the six-membered ring phosphates containing an O-isopropyl or O-1,1-dimethyl-3-butenyl functional group at C-6. The O-1,1-dimethyl-3-butenyl protecting group was efficiently removed after the phosphorylation with BF3.OEt2, and the six-membered cyclic phosphates containing free hydroxyl groups were obtained. A cyclic phosphate with a free hydroxyl group oriented cis to the phosphoryl group shows a vicinal coupling constant 3J(HP) that is in accordance with the chair conformation. This is due to the formation of a seven-membered intramolecular hydrogen-bonded ring structure that stabilizes the chair conformation. Thus, the strong tendency of the phenoxy group to be in an axial position is diminished by the internal hydrogen bonding interaction. Computational studies provided strong support for the experimental observation.

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Section: Resultsmentioning

confidence: 99%

Intramolecular Hydrogen Bonding (PO--H) Stabilizes the Chair Conformation of Six-Membered Ring Phosphates

et al. 2005

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“…4 Hz, 2 H), 2.44 (dt, J = 16.5, 1.3 Hz, 1 H), 1.61-1.48 (m, 2 ), 1.57 (s, 3 ), 0.92 (t, J = 7. 4 Hz, 3 H); MS, m/e (%) no M+, 149 (1), 144 (1), 143 (2), 142(1), 141 (2), 110 (49), 95 (14), 81 (100), 74 (33), 71 (13), 68 (26), 67 (11), 59 (65), 57 (11), 45 (25), 43 (53), 41 (11). exo-7-Ethyl-3-hydroxy-5-methyl-6,8-dioxabicyclo[3.2.1]octane (28).…”

Section: Methodsmentioning

confidence: 99%

Chelation-controlled facially selective cyclocondensation reactions of chiral alkoxy aldehydes: syntheses of a mouse androgen and of a carbon-linked disaccharide

Pearson¹,

Harvey²,

Maring³

et al. 1985

J. Am. Chem. Soc.

138

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Magnesium bromide in tetrahydrofuran catalyzes the cycloaddition of a variety of chiral alkoxy aldehydes with activated butadienes. The stereochemistry of these products is such that they can be rationalized as arising from a reacting conformer in which the alkoxy group is syn to the carbonyl function. The C=0 bond is attacked from its less hindered face.That chelation of the magnesium is involved in these reactions is indicated by a striking change from endo to exo topology as alkoxy functionality is introduced on the aldehyde. Titanium tetrachloride catalysis also provides excellent chelation-control stereoselectivity. The application of these findings to the synthesis of bridged ketals including the mouse androgen dehydrobrevicomin is described. Another application allows for the synthesis of carbon-linked disaccharides. BackgroundThe issue of diastereotopic preferences in the reactions of carbon nucleophiles with aldehydes or ketones has provoked considerable research1 and interpretation.2-6 Of course, nucleophilic addition to carbonyl groups is a central reaction type in organic chemistry.Thus, an insight into the relationship of chirality generated through such additions, with preexisting dissymmetry, is crucial to achieving stereochemical control in synthesis.

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“…Thermochemical experiments show that the 3',5'-cyclic nucleotides have an enthalpy of hydrolysis about 5 kcal/mol more exothermic than that found for methyl -D-glucopyranoside 4,6-cyclic phosphate and about 8 kcal/mol more exothermic than that observed for either trimethylene phosphate or 5-methoxytrimethylene phosphate.3 The excess enthalpy of hydrolysis of the cyclic nucleotides relative to the methyl glucoside cyclic phosphate is a measure of the geometric distortion in the former compounds relative to their hydrolysis products, since the crystal structure of the methyl glucoside cyclic phosphate revealed no evidence for geometric distortion.7 The difference between the enthalpies of hydrolysis of the monocyclic esters and the methyl glucoside cyclic phosphate can be explained as arising from solvation effects which result, in part, from the equatorial placement of the analogous oxygen atom in the glucoside cyclic phosphate. 5 We, therefore, consider this structure to be a striking illustration of the explanation for the unexpected exothermicity of hydrolysis of the methyl glucoside cyclic phosphate.20,21 Since the cyclic nucleotides also have an equatorial oxygen substituent at the central carbon atom of the cyclic phosphate ring, solvation effects presumably are also an important factor in their thermochemical behavior.…”

Section: Table II Bond Distances and Their Estimated Standard Deviati...mentioning

confidence: 99%

“…Oil--Pl-012 115.7 (1) 021--P2-022 115.8 (1) Oil--Pl-013 112.6 (1) 021--P2-023 110.8 (1) --Pl-014 109.4 (1) 021--P2-024 110. 5 (1) 2--Pl-013 104.7 (1) 022--P2-023 108.1 (1) 012--Pl-014 109.0 (1) 022--P2-024 104.8 (1) 013--Pl-014 104.9 (1) 023--P2-024 nitudes were those of the appropriate bond dipole moments. The atomic coordinates for the axial conformers used in these calculations were generated from the atomic coordinates determined for one of the two molecules in the asymmetric unit by successive 120°rotations about the C2-05 bond.…”

Section: Table II Bond Distances and Their Estimated Standard Deviati...mentioning

confidence: 99%

“…106.3 (1) Pl-013-Cll 117 5. (1) P2-023-C21119.1 (1) Pl-014-Cl 3 117.8 (1) P2-024-C23 118.2 (1) CH--015-C14 115.1 (2)C22--025-C24 115.5 (2) OIS•-C11-C12 110.9 (1) 023--C21-C22 111.2 (2) 015--Cl2-C11 107.5 (1) 025--C22-C21 106.8 (2) 015--C12-C13 113.5 (2) 025--C22-C23 112.7 (2) Cll--C12I-C13 111.3 (2) C21--C22-C23 111.1 (2) 014•-C13-C12 110.7 (1) 024--C23-C22 111.2 (2) 015--C14-C15 109.7 (2) 025--C24-C25 111.7 (2)…”

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Crystal and molecular structure of 5-ethoxytrimethylenephosphoric acid

et al. 1980

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The structure was solved by direct methods and refined to an R value of 0.040 for 2276 unique reflections. The cyclic phosphate rings of the two molecules in the asymmetric unit are both in chair conformations, and both ethoxy groups are oriented axially. A comparison of the structure of this monocyclic phosphodiester with the cyclic phosphodiesters found in glycoside cyclic phosphates, including 3',5'-cyclic nucleotides, reveals that the axial orientation of the ethoxy group observed in the present study and the equatorial orientation of the endocyclic glycoside oxygen atoms in the other cyclic esters is the most striking structural difference. This difference is important in the explanation for the unusual thermochemical behavior of the glycoside cyclic phosphates.

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Conformational properties of 5-alkoxy and 5-alkyl substituted trimethylene phosphates in solution

Cited by 14 publications

References 1 publication

Intramolecular Hydrogen Bonding (PO--H) Stabilizes the Chair Conformation of Six-Membered Ring Phosphates

Intramolecular Hydrogen Bonding (PO--H) Stabilizes the Chair Conformation of Six-Membered Ring Phosphates

Chelation-controlled facially selective cyclocondensation reactions of chiral alkoxy aldehydes: syntheses of a mouse androgen and of a carbon-linked disaccharide

Crystal and molecular structure of 5-ethoxytrimethylenephosphoric acid

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