Cyclitols have recently attracted a great deal of attention due to their diverse biological activiti — Physical Chemistry — Kinetics Chemistry Question
Cyclitols
Cyclitols have recently attracted a great deal of attention due to their diverse biological activities and their versatilities as synthetic intermediates. Polyhydroxy cyclohexanes, such as inositols, quercitols, and conduritols, belong to the family of cyclitols. These compounds can exist in a number of different stereoisomers; inositols, quercitols, and conduritols have 9, 16, and 6 possible stereoisomers, respectively.
Cyclohexa-1,3-diene (1) is an important key compound for the synthesis of versatile cyclitol derivatives. The total synthesis of isomeric cyclitols having the molecular formula C6H12O4 is shown below.
[VISUAL]
The reaction of cyclohexa-1,3-diene (1) with singlet oxygen O2(1Δg), generated in situ by irradiation of oxygen molecule in the presence of a sensitizer, yields an unstable bicyclic compound A. The reaction of A with LiAlH4 in ether results in the formation of B, whose 13C-NMR spectrum shows 3 resonances. One of them appears in the sp2 region.
Osmylation of B in the presence of an excess of NMO (N-morpholine oxide) (more than 2 equiv.) at room temperature in acetone/H2O leads to the isomeric mixture of C and D where the compound C is formed as the major product.
Oxidation of B with m-chloroperbenzoic acid (m-CPBA) gives a diastereomeric mixture of E and F. Treatment of this mixture with H2O in the presence of a catalytic amount of H2SO4 affords only compound G as a racemic mixture having the molecular formula of C6H12O4.
Draw the structures of A, B, C, D, E, F, and G using dashed-wedged line notation to indicate the relative configurations.
Model Answer
A: 2,3-dioxabicyclo[2.2.2]oct-5-ene (endoperoxide intermediate with a peroxide bridge)
B: cis-cyclohex-4-ene-1,2-diol
C: all-cis-cyclohexane-1,2,3,4-tetraol
D: trans,cis,trans-cyclohexane-1,2,3,4-tetraol (hydroxyl groups at C1/C2 are cis, at C3/C4 are cis, but the two pairs are trans relative to each other)
E: syn-3,4-epoxycyclohexane-1,2-diol (epoxide oxygen is cis to the adjacent cis-diols)
F: anti-3,4-epoxycyclohexane-1,2-diol (epoxide oxygen is trans to the adjacent cis-diols)
G: (1R,2R,3S,4S)-cyclohexane-1,2,3,4-tetraol (racemic mixture)
Osmylation of 1 in the presence of an excess of NMO (N-morpholine oxide) (more than 2 equiv.) at room temperature in acetone/H2O leads to the formation of a diastereomeric mixture of H and D where the compound H is formed as the major product.
[VISUAL]
Draw the structure of H using dashed-wedged line notation.
Model Answer
H: trans,cis,trans-cyclohexane-1,2,3,4-tetraol
Reaction of cyclohexa-1,3-diene (1) with 1 equiv. m-chloroperbenzoic acid (m-CPBA) gives a single product I, which is reacted with H2O in the presence of a catalytic amount of H2SO4 to provide J (There is no rearranged product).
Osmylation of J in the presence of excess of NMO (N-morpholine oxide) (more than 1 equiv.) at room temperature in acetone/H2O leads to formation of isomeric G and K.
[VISUAL]
Draw the structures of I, J, and K using dashed-wedged line notation.
Model Answer
I: 1,2-epoxycyclohex-3-ene
J: trans-cyclohex-5-ene-1,2-diol
K: 1,2-trans-3,4-cis-2,3-trans-cyclohexane-1,2,3,4-tetraol
Reaction of cyclohexa-1,3-diene (1) with 2 equiv. of m-chloroperbenzoic acid (m-CPBA) gives a diastereomeric mixture of L and M. Reaction of this mixture (L and M) with H2O in the presence of a catalytic amount of H2SO4 yields a mixture of N and C.
[VISUAL]
Draw the structures of L, M, and N using dashed-wedged line notation.
Model Answer
L: trans-1,2:3,4-diepoxycyclohexane
M: syn-1,2:3,4-diepoxycyclohexane
N: 1,4-cis-2,3-trans-cyclohexane-1,2,3,4-tetraol