Fillmore Freeman

Stereoselectivity in the electrophile-mediated cyclization of 2,3,5-tri-O-benzyl-1,2-dideoxy-D-arabino-hex-1-enitol: a stereocontrolled synthesis of 1-amino-2,5-anhydro-3,4,6-tri-O-benzyl-1-deoxy-D-glucitol

Abstract Cyclization of 2,3,5-tri-O-benzyl-1,2-dideoxy- d -arabino-hex-1-enitol (2) with mercuric acetate, mercuric trifluoroacetate, iodine, and N-bromosuccinimide gave preponderantly the allo isomer of the C-arabinofuranosyl structure. 1-Amino-2,5-anhydro-3,4,6-tri-O-benzyl-1-deoxy- d -glucitol, which is a key intermediate in the synthesis of 3-(β- d -arabinofuranosyl)pyrazole[4,3-d]pyrimidine-5,7-dione (β- d -arabino epimer of oxoformycin B), was stereoselectively prepared in 48% overall yield from 2 in three steps. The stereochemical outcome of the cyclizations is also discussed.

The Chemistry of 1,2-Dithiins

Abstract This report describes the bioactivity, the chemistry, and the synthesis of 1,2-dithiins, (o-dithiin, 1,2-dithia-3,5-cyclohexadiene) and its derivatives, including 1,2-benzodithiins, benzo[c]-1,2-dithiins (2,3-benzodithiins), dibenzo[c,e]-1,2-dithiins, 3,4-dihydro-1,2-dithiins, and 3,6-dihydro-1,2-dithiins.

Electrophile-mediated cyclizations in carbohydrate chemistry: synthesis of highly functionalized ribofuranose and ribopyranose compounds

Iodine-mediated cyclization of (Z)- and (E)-{=D}-ribohept-2-enonates 1 and 2 gave exclusively the β-ribofuranose and α-ribofuranose derivatives 3 and 4, respectively. Cyclization of the (Z)- and (E)-2-heptene-1-ol derivatives 5 and 6 gave ribofuranose products (7 and 8) and a ribopyranose (9), respectively.

Permanganate ion oxidations: IX. Manganese intermediates (complexes) in the oxidation of 2,4(1H,3H)-pyrimidinediones☆

Uniquely stable manganese intermediates (complexes) are formed from the permanganate ion oxidation of the 5,6-carbon-carbon double bond in several 2,4(1H,3H)-pyrimidinediones [uracil, (compound 7), 5-methyluracil (thymine, compound 5), and 6-methyluracil (compound 8)]. These manganese complexes, which represent some of the most stable intermediate manganese species observed thus far in the oxidation of carbon-carbon double bonds, show absorption maxima in the 285-296 nm region (epsilon max approximately 4500). The relative reactivities of 6-methyluracil: uracil: thymine are 1: 23 : 194 and the bimolecular oxidation process is characterized by relatively small deltaH++ values and large negative deltaS++ values.

Preparation of 2-alkyl- and 2-aryl-5-amino-4-cyano-1,3-oxazoles

Aminopropanedinitrile p-toluenesulfonate (aminomalononitrile tosylate, AMNT) reacts with acid chlorides to give 2-alkyl- and 2-aryl-5-amino-4-cyano-1,3-oxazoles in good to excellent yields.

An ab initio molecular orbital theory and density functional theory study of the conformational free energies of methyltetrahydro-2H-thiopyrans

Abstract Ab initio Hartree–Fock calculations using the 6-31G(d), 6-31G(2d), 6-31G(d,p), 6-311G(d,p), 6-31+G(d), and 6-311+G(d,p) basis sets, second-order Moller–Plesset perturbation theory (MP2) using the same basis sets, and density functional theory [SVWN/DN∗, SVWN/DN∗∗, pBP/DN∗, pBP/DN∗∗, BLYP/6–31G(d), B3BLYP/6–31G(d)] were used to calculate the geometry optimized structure of tetrahydro-2H-thiopyran (tetrahydrothiopyran, thiacyclohexane, thiane) and the conformational enthalpy (ΔH°), entropy (ΔS°), and free energy (ΔG°) of the chair conformers of methylcyclohexane and 2-methyl-, 3-methyl-, and 4-methyltetrahydro-2H-thiopyran. The DFT methods generally overestimate the conformational free energies (−ΔG°) while some of the MP2 methods give values closer to the experimental results. The MP2/6-311G(d,p) calculated value (− Δ G°=1.46 kcal/mol ) for 2-methyltetrahydro-2H-thiopyran is in excellent agreement with the experimentally reported value and the MP2/6-21G(2d) calculated value (− Δ G°=1.46 kcal/mol ) for 3-methyltetrahydro-2H-thiopyran is also in excellent agreement with the experimentally reported value. The equatorial preference of the methyl group is discussed in terms of the repulsive nonbonded interactions in the equatorial conformer, gauche butane (torsional) interactions in the axial conformer, and repulsive nonbonded interactions of the axial methyl group with the ring carbons and hydrogens.

Ab initio molecular orbital calculations of 3,4‐dihydro‐1,2‐dioxin, 3,6‐dihydro‐1,2‐dioxin, 4H‐1,3‐dioxin (1,3‐diox‐4‐ene), and 2,3‐dihydro‐1,4‐dioxin (1,4‐dioxene)

Optimized geometries and total energies for 3,4‐dihydro‐1,2‐dioxin (1), 3,6‐dihydro‐1,2‐dioxin (2), 4H‐1,3‐dioxin (1,3‐diox‐4‐ene, 3), and 2,3‐dihydro‐1,4‐dioxin (1,4‐dioxene, 4) were calculated using ab initio 3‐21G, 6‐31G*, and MP2/6‐31G*//6‐31G* methods. The half‐chair conformers of 1 (C1), 2 (C2), 3 (C1), and 4 (C2) are more stable than their respective planar structures [1 (Cs), 2 (C2v), 3 (Cs), and 4 (C2v)]. Among the four isomers 1–4, the half‐chair conformer of 3 is the most stable. It is 53.1, 54.6, and 3.4 kcal mol−1 more stable than 1, 2, and 4, respectively. The largest energy difference (19.0 kcal mol−1) is observed between the half‐chair and planar conformers of 2. The boat conformers of 2 and 4 are less stable than their respective half‐chair conformers, but are more stable than their planar structures. Hyperconjugative orbital interactions (anomeric effects) contribute to the greater stability of 3(nO(3) →σ*C(2)—O(1), nO(3)→σ*  C(2)—H ax ,n O(3)→σ*  C(2)—H ax ) and of 4 (nO(1)→ σ*  C(2)—H ax ). The ab initio calculated structural features of the half‐chair conformations of the dihydrodioxins 1–4 are compared with the half‐chair conformations of cyclohexene and the chair conformations of cyclohexane, oxacyclohexane (tetrahydropyran), 1,2‐dioxacyclohexane (1,2‐dioxane), 1,3‐dioxacyclohexane (1,3‐dioxane), and 1,4‐dioxacyclohexane (1,4‐dioxane) © 1997 by John Wiley & Sons, Inc. J Comput Chem 18: 1392–1406, 1997

A computational study of conformational interconversions in 1,4‐dithiacyclohexane (1,4‐dithiane)

Ab initio molecular orbital theory with the 6‐31G(d), 6‐31G(d,p), 6‐31+G(d), 6‐31+G(d,p), 6‐31+G(2d,p), 6‐311G(d), 6‐311G(d,p), and 6‐311+G(2d,p) basis sets and density functional theory (BLYP, B3LYP, B3P86, B3PW91) have been used to locate transition states involved in the conformational interconversions of 1,4‐dithiacyclohexane (1,4‐dithiane) and to calculate the geometry optimized structures, relative energies, enthalpies, entropies, and free energies of the chair and twist conformers. In the chair and 1,4‐twist conformers the CHax and CHeq bond lengths are equal at each carbon, which suggest an absence of stereoelectronic hyperconjugative interactions involving carbon–hydrogen bonds. The 1,4‐boat transition state structure was 9.53 to 10.5 kcal/mol higher in energy than the chair conformer and 4.75 to 5.82 kcal/mol higher in energy than the 1,4‐twist conformer. Intrinsic reaction coordinate (IRC) calculations showed that the 1,4‐boat transition state structure was the energy maximum in the interconversion of the enantiomers of the 1,4‐twist conformer. The energy difference between the chair conformer and the 1,4‐twist conformer was 4.85 kcal/mol and the chair‐1,4‐twist free energy difference (ΔG°c‐t) was 4.93 kcal/mol at 298.15 K. Intrinsic reaction coordinate (IRC) calculations connected the transition state between the chair conformer and the 1,4‐twist conformer. This transition state is 11.7 kcal/mol higher in energy than the chair conformer. The effects of basis sets on the 1,4‐dithiane calculations and the relative energies of saturated and unsaturated six‐membered dithianes and dioxanes are also discussed.

An ab initio molecular orbital study of the conformational energies of 2-alkyltetrahydro-2H-pyrans (tetrahydropyrans, oxacyclohexanes, oxanes)

Abstract Ab initio Hartree–Fock and Density Functional Theory calculations were used to obtain the geometries and relative energies of the rotamers in the chair conformations of 2-alkyltetrahydro-2 H -pyrans and 2-(trimethylsilyl)tetrahydro-2 H -pyran. The MP2/6-31G*//6-31G* conformational energies (−ΔG°or A values, kcal/mol) of the 2-alkyltetrahydro-2 H -pyrans (Me=3.18; Et=3.04; i -Pr=3.03; t -Bu=7.56; neo Pent=2.84) and 2-(trimethylsilyl)tetrahydro-2 H -pyran (SiMe 3 =4.77) are larger than those calculated for the corresponding alkylcyclohexanes and 2-alkyltetrahydro-2 H -thiopyrans (tetrahydrothiopyrans, thiacyclohexanes, thianes). Plots of the calculated conformational energies for the 2-substituted tetrahydro-2 H -pyrans versus the calculated −ΔG° values for the corresponding alkylcyclohexanes (slope=1.34 and r =0.983) and for the corresponding 2-substituted tetrahydro-2 H -thiopyrans (slope=2.01 and r =0.986) are linear.

Ab initio molecular orbital calculations for 3,6-dihydro-1,2-dithiin and 3,6-dihydro-1,2-dioxin

Optimized geometries and total energies for the conformers of 3,6‐dihydro‐1,2‐dithiin (2) and 3,6‐dihydro‐1,2‐dioxin (3) were calculated at several ab initio MO levels: RHF/3‐21G(*), RHF/6‐31G*, MP2/6‐31G*, and MP2/6‐31G*/ /RHF/3‐21G(*). For the dioxin, in addition to the above levels the corresponding nonextended basis sets ab initio methods were also carried out. The dithiin results are compared with those of simple disulfanes, HSSH and (CH3)2S2, whose optimized geometries agree closely with the observed structures, which is the gauche (C2 symmetry). For the disulfanes, the gauche geometries from RHF/3‐21G(*) are in good agreement with the observed structure while the RHF/3‐21G results best fit the dioxin. Pertinent structural data at the RHF/3‐21G(*) for the half‐chair (C2) dithiin are: bond lengths, SS, CS, CC, and CC, 2.050, 1.817, 1.515, and 1.317 Å, respectively; bond angles, CSS, CCS, and CCS, 98.0, 114.2, and 127.8°, respectively; CSSC dihedral angle of 63.2°; and twist angle of 36.5°. The total energy for half‐chair dithiin at MP2/6‐31G*//RHF/3‐21G(*) is less than the planar (C2v) and the half‐boat (Cs) structures by 69.67 and 29.05 kJ/mol, respectively. The calculated structural data (vs. observed) at RHF/3‐21G for the half‐chair dioxin are: bond lengths, OO, CO, CC, and CC, 1.464 (1.463), 1.454, 1.509, and 1.313 Å (1.338 Å), respectively; bond angles, COO, CCO, and CCO, 105.0, 109.8 (110.3), and 120.7° (119.9°), respectively; COOC dihedral angle of 79.7° (80 ± 2°); and twist angle of 39.0 (38.3°). The total energy for half‐chair dioxin at MP2/6‐31G//RHF/3‐21G is less than the planar and the half‐boat structures by 70.35 and 42.85 kJ/mol, respectively. The total energies calculated at the extended basis sets (*) ab initio levels for the C2 symmetry dioxin are much lower than those of the nonextended basis sets.