Molecular modeling boat conformations

Deuterium atom was neatly incorporated at the bridgehead position C-l in ketone 464, the only compound in which the cyclohexane ring is locked in a boat conformation. Examination of molecular models indicates that the cyclohexanone ring can easily adopt a boat form in 460 and 461. It appears to be more difficult with ketone 462 and almost impossible with ketone 463. 

The broken lines in the diagrams show the trace of the plane of the n orbitals. A reaction will occur readily if X lies on this plane and makes an obtuse angle with the C=Y bond. Molecular models show that the carbon backbone is long and flexible enough to satisfy both of these criteria for the exo reactions. The 6-endo reaction poses problems. If X lies in the n plane, the carbon skeleton has to adopt a boat conformation, leading to a perpendicular attack. However, if X moves slightly out of the n plane, an acceptable compromise can be achieved the attack trajectory becomes non-perpendicular, with a fair nucleophile-n overlap. However, neither condition can be satisfied for a 5-endo reaction. Note that a direct application of Baldwin s empirical rules would have masked these subtleties. 

Wallis and Thompson [61] developed a potential energy surface using these spectroscopic and theoretical data and used it in molecular dynamics simulations to study the chair-to-boat conformational inversion. They followed up this study with simulations of the RDX conformational changes in dense xenon gas as a function of concentration. Since then a great deal more has been learned about the details of the potential from quantum chemistry calculations and could be used to improve the Wallis-Thompson model. 

The two chair conformations of methylcyclohexane interconvert at room temperature, so the one that is lower in energy predominates. Careful measurements have shown that the chair with the methyl group in an equatorial position is the most stable conformation. It is about 7.6 kJ/mol (1.8 kcal/mol) lower in energy than the conformation with the methyl group in an axial position. Both of these chair conformations are lower in energy than any boat conformation. We can show how the 7.6 kJ energy difference between the axial and equatorial positions arises by examining molecular models and Newman projections of the two conformations. First, make a model of methylcyclohexane and use it to follow this discussion. 

Norbomane has a conformationally locked boat cydohexane- ring in which carbons 1 nnd -1 are joined by an extra CHj KTouP- Note how. in draw ing this structure, a break in the rear bond indicates that the veritca) bond crosses in front of it. Making a molecular model is particulariy helpful when trying to see the three dimensionAltty of norbomane. 

It is easy to see from inspection of molecular models that two distinct conformations of cyclohexane can be formed when the tetrahedral angle is maintained at each carbon atom. These are called the boat and chair conformations because of their resemblance to these objects (Fig. 7.7). The chair conformation has four carbon atoms in a plane with one above and one below that plane, located on opposite sides of the molecule. The boat conformation also has four carbon atoms in a plane, but both of the remaining atoms are located above this plane. Both conformations exist and appear to interconvert rapidly at room temperature through a sequence of rotations about single bonds (see Fig. 7.2). The chair conformation is significantly more stable than the boat, because the hydrogen atoms can become... 

The boat conformation of cyclohexane (18) can be constructed from a molecular model of the chair form by holding the right-hand three carbons C(2), C(3) and C(4) of 15, clamped from the top with the hand and moving the left-hand three carbons upward. A Newman projection of the boat form looking along the C(l)-C(2) bond, and shown in 19, is reminiscent of the highest energy cis conformation of butane. 

Make a molecular model of 30 and confirm that closure of the second ring gives 34. After the ring closure, convince yourself that /rf//rv-decalm is rigid around the ring junction. It is possible only to flex the extremities of each six-membered ring in the model, to form mono- or di-boat conformations. 

B. Coxon, Boat conformations Synthesis, NMR spectroscopy, and molecular modeling of methyl 2,6-anhydro-3-deoxy-3-phthalimido-a-D-mannopyranoside and its 15N-labeled analog, Carbohydr. Res., 322 (1999) 120-127. 

In 1974 Trippett (35) made the interesting observation from molecular models that the boat conformation for a six-membered ring located (a-e) in an oxyphosphorane is the most stable since it is the only one that positions the lone pair of electrons on the equatorial ring oxygen atom in the favored equatorial plane for k back-bonding to empty phosphorus d orbitals. For this requirement to be met, the dihedral angle... 

Mechanistically, the requisite betaine intermediates [from dioxaphospholanes N and O] adopt either the chair ( C -> 4) or twist-boat ( 85, 82) conformations so that the C-O" and -O-+PPh3 groups can assume the requisite pre-transition state andperiplanar arrangement for suitable displacement of Ph3PO. From the results of molecular modeling studies (/.e., MacroModel II) on both the chair e.g., IC4) and twist-boat betaine e.g., 85, 82) conformers, the small energy differences between them suggest that the twist-boat ( 85 and 82) betaine conformers may also be... 

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