The HERON rearrangement in an amino alkoxy formamide

Links to paper:Text,  Table, Fig 1, Fig 2, Fig 3, Fig 4, Fig 5, Fig 6a, Fig 6b, Fig 7.

Structure 1 exists predominantly in two conformations: (Z)-1 and (E)-1 (Erel = 6.4 kJ/mol.)

(Z)-1(1A) ...(E)-1(1D) 

1A: For (Z)-1, E = -418.29799, ZPVE = 397.2 kJ/mol: r(C-N1) = 1.387, r(N1-N2) = 1.385, r(N1-O) = 1.426. This is the lowest energy conformation.

1D: For (E)-1, E = -418.29529, ZPVE = 396.5 kJ/mol.: r(C-N1) = 1.397, r(N1-N2) = 1.376, r(N1-O) = 1.456. (E)-1 is 6.4 kJ/mol less stable than (Z)-1.
(Z)-2(1B) ...(E)-2(1C) 

1B: For (Z)-2, E = -418.28921, ZPVE = 396.3 - This at +22.2 kJ/mol rel to Z-1 (1A).

1C: For (E)-2, E = -418.29589, ZPVE = 397.3 kJ/mol.  - This at +5.5 kJ/mol rel to Z-1 (1A).
 

Z-1 and E-1 are interconverted by two acyl rotation transition structures,TSexo-1 and TSendo-1, The activation barrier (DH at 0K) over the exo and endo TSs are 52.8 kJ/mol and 61.9 kJ/mol, respectively. These energies include zero-point vibrational energies scaled by 0.98.

TSexo-1 ...TSendo-1 

For TSexo-1, E = -418.27648, ZPVE = 393 kJ/mol, IMAG = 132i: r(C-N1) = 1.456, r(N1-N2) = 1.394, r(N1-O) = 1.484. This is the lower energy acyl rotation transition structure.

For TSendo-1, E = -418.27288, ZPVE = 393 kJ/mol, IMAG = 266i: r(C-N1) = 1.465, r(N1-N2) = 1.391, r(N1-O) = 1.482. This is the higher energy acyl rotation transition structure.

No transition structure for N1 inverion could be located. I believe that this process is unhindered even though the geometry at N1 is a shallow pyramid.

Two transition structures,N1N2TSexo-1 and N1N2TSendo-1 , for N1-N2 rotation have been located so far. The activation barriers are 58 kJ/mol and 60 kJ/mol, respectively, without ZPE correction. For the first, ZPE correction makes no difference. I will not do frequencies for the second. Thus the barriers are about the same as for acyl rotation. Both N1 and N2 are steeper pyramids with the lone pairs anti.

N1N2TSexo-1 ...N1N2TSendo-1 

For N1N2TSexo-1, E = -418.27513, ZPVE = 397 kJ/mol, IMAG = 81i: r(C-N1) = 1.395, r(N1-N2) = 1.475, r(N1-O) = 1.404. This is the higher? energy N1-N2 rotation transition structure.

For N1N2TSendo-1, E = -418.27595, ZPVE = ??? kJ/mol, IMAG = ???i: r(C-N1) = 1.379, r(N1-N2) = 1.477, r(N1-O) = 1.389. This is the higher energy N1-N2 rotation transition structure.

Two transition structures,N1OTS_E-1 and N1OTS_Z-1 , for N1-O rotation have been located so far. The activation barriers are 28 kJ/mol and 53 kJ/mol, respectively, without ZPE correction. Frequencies for the first are under way. I will not do frequencies for the second. Both structures have Cs symmetry (N1 is flat). The higher TS has the three methyl groups quite crowded.

N1OTS_E-1 ...N1OTS_Z-1 

For N1OTS_E-1, E = -418.28743, ZPVE = ??? kJ/mol, IMAG = ???1i: r(C-N1) = 1.368, r(N1-N2) = 1.372, r(N1-O) = 1.433. This is the lower energy N1-O rotation transition structure.

For N1OTS_Z-1, E = -418.27789 : r(C-N1) = 1.378, r(N1-N2) = 1.350, r(N1-O) = 1.454. This is the higher energy N1-O rotation transition structure.

A transition structure for N2 inversion,N2TS_Z-1 has been located. It connects with a second (Z) isomer, Z2-1 which is 23.1 kJ/mol higher, The activation barrier from N2TS_Z-1 is 30.3 kJ/mol, without ZPE correction. Frequencies for the TS are under way. I will not do frequencies for the second Z isomer.

N2TS_Z-1 ...Z2-1 

For N2TS_Z-1, E = -418.28644, ZPVE = ??? kJ/mol, IMAG = ???1i: r(C-N1) = 1.387, r(N1-N2) = 1.354, r(N1-O) = 1.429.

For Z2-1, E = -418.28921 : r(C-N1) = 1.385, r(N1-N2) = 1.397, r(N1-O) = 1.405. .

The geometric and energetic data suggest some interesting comments on the anomeric effect. The nN2-s*N1O interaction dominates and determines the most stable conformation. The reverse effect, nO-s*N1N2 does not seem to be operating since the CONN dihedral angle is not close to 90o. In fact, the CONC dihedral angle is close to 90o. One would have to say that the orientaion of the MeO bond is a consequence of minimizing the nO-nN1 four electron repulsion. However, in the N2-inverted conformation, Z2-1, the nN2-s*N1O is much less favourable because of the poor orientation of nN2. The N1-N2 bond is longer, bringing the s*N1N2 orbital lower. In fact, the CONN angle is now almost exactly 90o suggesting that the nO-s*N1N2 interaction is more important. Of course, the energy cost of swapping these two around is 23 kJ/mol, the difference between Z-1 and Z2-1.

A transition structure, TS-1, for the rearrangement of (Z)-1 to a complex, C-1, between methyl formate and N,N-dimethylaminonitrene was located. The activation barrier (DH at 0K) from (Z)-1 is 90.1 kJ/mol. The rearrangement from (Z)-1 to C-1 is slightly exothermic, DH(0K) = -23.4 kJ/mol. C-1 is bound relative to the separated species by 6.7 kJ/mol. These energies include zero-point vibrational energies scaled by 0.98.

TS-1 ...C-1 

TS-1: E = -418.26169, ZPVE = 391.9 kJ/mol, imaginary frequency = 201i cm-1: E(rel to (Z)-1) is 95.3 kJ/mol without ZPVE and 90.1 kJ/mol including the scaled (x0.98) ZPVE.

C-1: -418.30272, ZPVE = 386.0 kJ/mol (the sum of methyl formate and the nitrene): : E(rel to (Z)-1) is -12.4kJ/mol without ZPVE and -23.4kJ/mol including the scaled (x0.98) ZPVE. The N is 3.37 A from the ether oxygen of methyl formate.

The IRC connecting (Z)-1 to C-1 via TS-1. In the (Z)-1 to C-1 direction, the methoxy migration step is preceeded by a rotation about the amide C-N bond which takes the acyl group out of conjugation with the N lone pair and orients the pi* orbital of the acyl group into position to receive the non-bonded electrons of the oxygen.

TS-2 

TS-2: E = -418.26494, ZPVE = 392.0 kJ/mol, imaginary frequency = 101.6i cm-1: E(rel to (Z)-1) is 86.8 kJ/mol without ZPVE and  80.7 kJ/mol including the scaled (x0.98) ZPVE.

TS-3  TS-3: E = -418.25058, ZPVE = 390.6 kJ/mol, imaginary frequency = 168i cm-1: E(rel to (Z)-1) is 118.0 kJ/mol including the scaled (x0.98) ZPVE.

TS-4  TS-4: E = -418.26617, ZPVE = 391.4 kJ/mol, imaginary frequency = 186i cm-1: E(rel to (Z)-1) is 77.9 kJ/mol including the scaled (x0.98) ZPVE.

N-Formyl-N-methoxyaminonitrene (NMO)
(Z,Z)-NMO .. (E,Z)-NMO ..

NMO exists as two conformers differing by the orientation of the formyl group.  Only the (Z) orientation of the methoxy group is stable - thus attempts to optimize to (Z,E)-NMO resulted in (Z,Z)-NMO, and likewise, starting from (E,E)-NMO gave (E,Z)-NMO.
(Z,Z)-NMO: E = --338.43635, ZPVE = 181.1 kJ/mol: r(N=N) = 1.156 A; r(=C-N-) = 1.506 A; r(N-O) = 1.668 A.  Note the long =C-N and N-O distances..
(E,Z)-NMO: E = --338.43311, ZPVE = 181.8 kJ/mol: r(N=N) = 1.176 A; r(=C-N-) = 1.503 A; r(N-O) = 1.539 A.

A transition structure, NMO-TS, for the rearrangement of (Z,Z)-NMO to N2 +  methyl formate  was located. The activation barrier (DH at 0K) from (Z,Z)-NMO is 16.6 kJ/mol. . These energies include zero-point vibrational energies scaled by 0.98.

NMO-TS ... 

NMO-TS: E = -338.43068, ZPVE = 178.2 kJ/mol, imaginary frequency = 181i cm-1: E(rel to (Z,Z)-NMO) is 16.6 kJ/mol  including the scaled (x0.98) ZPVE.

The IRC connecting (Z,Z)-NMO to methyl formate and N2 via NMO-TS. In the (Z)-1 to C-1 direction, the methoxy migration step is preceeded by a rotation about the amide C-N bond which takes the acyl group out of conjugation with the N lone pair and orients the pi* orbital of the acyl group into position to receive the non-bonded electrons of the oxygen.
 

Methyl formate ..

Methyl formate: E = -229.06301, ZPVE = 164.1 kJ/mol: r(C=O) = 1.206 A; r(=C-O-) = 1.342 A; r(O-CH3) = 1.441 A.

N,N-Dimethylaminonitrene 

N,N-Dimethylaminonitrene: E = -189.23714, ZPVE = 221.9 kJ/mol: r(NN) = 1.214 A; r(CN) = 1.510 A.

Related Publications

• A. Rauk and S. A. Glover, a Computational Study of Bisheteroatom Substituted Amides - Structure and Stereochemistry, J. Org. Chem., 61, 2337-2345 (1996).