Determination of absolute configuration remains a difficult undertaking, one usually solved by x-ray crystallography. In my book (Chapter 1.6.3) and blog (see these posts) I have noted the use of computations in conjunction with optical rotation or electronic circular dichroism as an alternative: possible configurations are optimized and their optical properties are computed and then matched against experimental spectra.

Neri and coworkers have utilized this approach to determine the absolute configuration of the chiral calix[4]arene 1.¹

Computed optical rotations (TDDFT/B3LYP/6-31G* at 5 frequencies) are compared with experimental values in Table 1. While the magnitude is off (as is typical) the sign of the activity along with the trend matches up very well for the cS configuration shown in Figure 1. It should be noted that a second conformation makes up about 10% of the Boltzmann population, and the contribution of this second configuration is included in the computed values shown in Table 1. In addition, computations at higher levels give very similar results. Lastly, the computed ECD spectrum of the cS isomer also matches up well with experiment.

Table 1. Optical rotation of the cS isomer of 1 compared with experiment

Figure 1. B3LYP/6-31G* optimized structure of the major conformation of 1.

Given the relatively low level of theory employed here, further use of this combined experimental/computational approach to obtaining absolute configurations of large molecules is encouraged.

References

(1) Talotta, C.; Gaeta, C.; Troisi, F.; Monaco, G.; Zanasi, R.; Mazzeo, G.; Rosini, C.; Neri, P., "Absolute Configuration Assignment of Inherently Chiral Calix[4]arenes using DFT Calculations of Chiroptical Properties," Org. Lett., 2010, 12, 2912-2915, DOI: 10.1021/ol101098x

InChIs

1: InChI=1/C59H78O7/c1-16-19-64-53-36-22-35-32-47(59(13,14)15)50(51-48(61)33-45(60)34-49(51)62)46(52(35)63)31-41-30-44(58(10,11)12)29-40(55(41)66-21-18-3)24-39-28-43(57(7,8)9)27-38(54(39)65-20-17-2)23-37(53)26-42(25-36)56(4,5)6/h25-30,32-34,60-63H,16-24,31H2,1-15H3
InChIKey=VGWOVZXMYMCPQO-UHFFFAOYAS

Since Heilbronner¹ proposed the Möbius annulene in 1964, organic chemists have been fascinated with this structure and many have tried to synthesize an example. I have written many blog posts (1, 2, 3, 4, 5) related to computed Möbius compounds. Now, Herges and Grimme and co-workers have looked at cationic Möbius annulenes.

For the [9]annulene cation,² a variety of DFT methods, along with SCS-MP2 and CCSSD(T) computations suggest that the lowest energy Hückel (1h) and Möbius (1m) structures, shown in Figure 1, are very close in energy. In fact, the best estimate (CCSD(T)/CBS) is that they differ by only 0.04 kcal mol^-1. Laser flash photolysis of 9-chlorobicyclo[6.1.0]nona-2,4,6-triene suggest however that only the Hückel structure is formed, and that its short lifetime is due to rapid electrocyclic ring closure.

In a follow-up study, Herges has examined the larger annulene cations, specifically [13]-, [17]- and [21]-annulenes. ³ The Möbius form of [13]-annulene cation (2m) is predicted to be 11.0 kcal mol^-1 lower in energy that the Hückel (2h) form at B3LYP/6-311+G**. The structures of these two cations are shown in Figure 1. The Möbius cation 2m is likely aromatic, having NICS(0)= -8.95. Electrocyclic ring closure of 2m requires passing through a barrier of at least 20 kcal mol^-1, suggesting that 2m is a realistic target for preparation and characterization.

1h	1m
2h	2m

Figure 1. Optimized structures of 1 (CCSD(T)/cc-pVTZ)² and 2 (B3LYP/6-311+G**)³.

The energy difference between the Möbius and Hückel structures of the larger annulenes is very dependent on computational method, but in all cases the difference is small. Thus, Herges concludes that [13]-annulene cation should be the sole target of synthetic effort toward identification of a Möbius annulene. Experimental studies are eagerly awaited!

References

(1) Heilbronner, E., “Huckel molecular orbitals of Mobius-type conformations of annulenes,” Tetrahedron Lett., 1964, 5, 1923-1928, DOI: 10.1016/S0040-4039(01)89474-0.

2) Bucher, G.; Grimme, S.; Huenerbein, R.; Auer, A. A.; Mucke, E.; Köhler, F.; Siegwarth, J.; Herges, R., "Is the [9]Annulene Cation a Möbius Annulene?," Angew. Chem. Int. Ed., 2009, 48, 9971-9974, DOI: http://dx.doi.org/10.1002/anie.200900886

(3) Mucke, E.-K.; Kohler, F.; Herges, R., "The [13]Annulene Cation Is a Stable Mobius Annulene Cation," Org. Lett., 2010, 12, 1708–1711, DOI: 10.1021/ol1002384

InChIs

1: InChI=1/C9H9/c1-2-4-6-8-9-7-5-3-1/h1-9H/q+1/b2-1-,5-3-,6-4-,9-7-
InChIKey=LIUDWUIEJKKGNI-BWYSQNKRBF

2: InChI=1/C13H13/c1-2-4-6-8-10-12-13-11-9-7-5-3-1/h1-13H/q+1/b2-1-,5-3-,6-4-,9-7-,10-8-,13-11-
InChIKey=FUBPZYTZTJGXKZ-OGBOFXOGBR

The nature of reactions of indolynes is the subject of two recent computational/experimental studies. There are three isomeric indolynes 1a-c which are analogues of the more famous benzyne (which I discuss in significant detail in Chapter 4.4 of my book).

One might anticipate that the indolynes undergo comparable reactions as benzyne, like Diels-Alder reactions and nucleophilic attack. In fact the indolynes do undergo these reactions, with unusual regiospecificity. For example, the reaction of the substituted 6,7-indolyne undergoes regioselective Diels-Alder cycloaddition with substituted furans (Scheme 1), but the reaction with the other indolynes gives no regioselection. ¹ Note that the preferred product is the more sterically congested adduct.

Scheme 1

In the case of nucleophilic addition, the nucleophiles add specifically to C₆ with substituted 6,7-indolynes (Scheme 2), while addition to 4,5-indolynes preferentially gives the C₅-adduct (greater than 3:1) while addition to the 5,6-indolynes preferentially gives the C₅-adduct), but with small selectivity (less than 3:1).²

Scheme 2

The authors of both papers – Chris Cramer studied the Diels-Alder chemistry and Ken Houk studied the nucleophilic reactions – employed DFT computations to examine the activation barriers leading to the two regioisomeric products. So for example, Figure 1 shows the two transition states for the reaction of 2c with 2-iso-propyl furan computed at MO6-2X/6-311+G(2df,p).

ΔG‡ = 9.7

ΔG‡ = 7.6

Figure 1. MO6-21/6-311+G(2df,p) optimized TSs for the reaction of 2-iso-propylfuran with 2c. Activation energy (kcal mol^-1) listed below each structure.¹

The computational results are completely consistent with the experiments. For the Diels-Alder reaction of 2-t-butylfuran with the three indolynes 2a-c, the lower computed TS always corresponds with the experimentally observed major product. The difference in the energy of the TSs leading to the two regioisomers for reaction with 2a and 2b is small (less than 1 kcal mol^-1), consistent with the small selectivity. On the other hand, no barrier could be found for the reaction of 2-t-butylfuran with 2c that leads to the major product. Similar results are also obtained for the nucleophilic addition – in all cases, the experimentally observed major product corresponds with the lower computed activation barrier.

So what accounts for the regioselectivity? Both papers make the same argument, though couched in slightly different terms. Houk argues in terms of distortion energy – the energy needed to distort reactants to their geometries in the TS. As seen in Figure 2, the benzyne fragment of 2a is distorted, with the C-C-C angle at C₄ of 125° and at C₅ of 129°. In the transition states, the angle at the point of nucleophilic attack widens. Since the angle starts out wider at C₅, attack there is preferred, since less distortion is needed to achieve the geometry of the TS.

2a
TS at C4 ΔG‡ = 12.9	TS at C5 ΔG‡ = 9.9

Figure 2. B3LYP/6-31G(d) optimized structures of 2a and the TSs for the reaction of aniline with 2a. Activation energy in kcal mol^-1.²

Cramer argues in terms of the indolyne acting as an electrophile. Increasing substitution at the furan 2-position makes is better at stabilizing incipient positive charge that will build up there during a (very) asymmetric Diels-Alder transition state. This explains the increasing selectivity of the furan with increasing substitution. The indolyne acting as an electrophile means that the attack will lead from the center will lesser charge. In 2c, the C-C-C angle at C₆ is 135.3°, while that at C₇ is 117.2°. This makes C₇ more carbanionic and C₆ more carbocationic; therefore, the first bond made is to C₆, leading to the more sterically congested product. Note that Houk’s argument applies equally well, as C₆ is predistorted to the TS geometry.

References

(1) Garr, A. N.; Luo, D.; Brown, N.; Cramer, C. J.; Buszek, K. R.; VanderVelde, D., "Experimental and Theoretical Investigations into the Unusual Regioselectivity of 4,5-, 5,6-, and 6,7-Indole Aryne Cycloadditions," Org. Lett., 2010, 12, 96-99, DOI: 10.1021/ol902415s

(2) Cheong, P. H. Y.; Paton, R. S.; Bronner, S. M.; Im, G. Y. J.; Garg, N. K.; Houk, K. N., "Indolyne and Aryne Distortions and Nucleophilic Regioselectivites," J. Am. Chem. Soc., 2010, 132, 1267-1269, DOI: 10.1021/ja9098643

InChIs

1a: InChI=1/C8H5N/c1-2-4-8-7(3-1)5-6-9-8/h2,4-6,9H
InChIKey=RNDHGGYOIRREHC-UHFFFAOYAU

1b: InChI=1/C8H5N/c1-2-4-8-7(3-1)5-6-9-8/h3-6,9H
InChIKey=WWZQFJXNXMIWCD-UHFFFAOYAO

1c: InChI=1/C8H5N/c1-2-4-8-7(3-1)5-6-9-8/h1,3,5-6,9H
InChIKey=UHIRLIIPIXHWLT-UHFFFAOYAH

2a: InChI=1/C9H7N/c1-10-7-6-8-4-2-3-5-9(8)10/h3,5-7H,1H3
InChIKey=VTVUPAJGRVFCKI-UHFFFAOYAJ

2b: InChI=1/C9H7N/c1-10-7-6-8-4-2-3-5-9(8)10/h4-7H,1H3
InChIKey=KKPOWDDYMOXTFW-UHFFFAOYAN

2c: InChI=1/C9H7N/c1-10-7-6-8-4-2-3-5-9(8)10/h2,4,6-7H,1H3
InChIKey=MDAHOGWZOBLIEX-UHFFFAOYAZ

Here’s another attempt (almost successful!) in creating a planar cyclooctatetraene. Nishininaga and Iyoda have fused silicon and sulfur bridges to the COT framework, hoping to force the 8-member ring out of its preferred tub-shape into a planar structure.¹ They report the synthesis of 1, 2, and 3b along with their x-ray structures. They also calculated the structures at B3LYP/6-31G(d,p) for 1-4 , and these optimized structures are shown in Figure 1.

1 18° 19°	2 3.0° 4.3°
3a 7.0° (for 3b) 3.2° (for 3a)	4 39° 40°

Figure 1. B3LYP/6-31G(d,p) optimized geometries of 1-4. The experimental (top) and computed (Bottom in italics) value of α are listed for each compound.¹

The bent angle α is defined at the angle between the two planes that define the bottom of the tub and one of the sides. For COT itself, this angle is 40°, decidedly non-planar – as expected for a molecule avoiding the antiaromatic character it would have in its planar conformation. The computed and experimental values of α are shown in Figure 1. 4 is tub shaped. The value of α for 1 is about 18° – still tub shaped but flattened. But 2 and 3 are nearly planar, with experimental values of α about 3° and the computed values are similar.

So what is the character of the 8-member ring in these compounds. The computed NICS(0) values are 3.8 ppm for 4, the expected small value for a non-aromatic compound. (Note that the NICS value for COT is 2.9 ppm.) The values are much more positive for the other compounds: 12.7 ppm for 1, 17.4 ppm for 2, and 15.4 ppm for 3a. These compounds therefore display antiaromatic character yet they are isolable compounds!

References

(1) Ohmae, T.; Nishinaga, T.; Wu, M.; Iyoda, M., "Cyclic Tetrathiophenes Planarized by Silicon and Sulfur Bridges Bearing Antiaromatic Cyclooctatetraene Core: Syntheses, Structures, and Properties," J. Am. Chem. Soc., 2009, 132, 1066-1074, DOI: 10.1021/ja908161r

InChIs

1: InChI=1/C20H16S4Si2/c1-25(2)9-5-21-17-13(9)14-10(25)6-22-18(14)20-16-12(8-24-20)26(3,4)11-7-23-19(17)15(11)16/h5-8H,1-4H3/b19-17-,20-18-
InChIKey=DAVVQYAXJVCICC-CLFAGFIQBV

2: InChIKey=PBXVOLKKILUEGI-RFIZXXDFBX

3a: InChI=1/C16H4O4S6/c17-25(18)5-1-21-13-9(5)10-6(25)2-23-15(10)16-12-8(4-24-16)26(19,20)7-3-22-14(13)11(7)12/h1-4H/b14-13-,16-15-
InChIKey=VIDZCGPUBZEACC-RFIZXXDFBR

3b: InChI=1/C28H36O4S6Si4/c1-39(2,3)25-21-13-14-19(35-26(40(4,5)6)22(14)37(21,29)30)20-16-15-18(17(13)33-25)34-27(41(7,8)9)23(15)38(31,32)24(16)28(36-20)42(10,11)12/h1-12H3/b18-17-,20-19-
InChIKey=XXCFCYWSFICMIO-RXGVRZIVBS

4: InChI=1/C16H8S4/c1-5-17-13-9(1)10-2-6-18-14(10)16-12(4-8-20-16)11-3-7-19-15(11)13/h1-8H/b10-9-,12-11-,15-13-,16-14-
InChIKey=RSNUTSCZGMAXQJ-FNJUYVFOBD

Dewar benzene has fascinated physical organic chemists for a long time. Just how does this open up? And why is is stable, given its large strain and the aromaticity of the ring-opened product? Most had rationalized this by recognizing that the route that takes Dewar benzene into benzene is the symmetry-forbidden disrotatory path, and the symmetry allowed conrotatory path leads to the benzene with a trans double bond.

Johnson¹ discovered that the conrotatory TS is high in energy, but below the C_2v structure thought to be the disrotatory TS, but is in fact a saddle point. Further, the IRC path through the conrotatory TS connects Dewar benzene to benzene, avoiding the trans-benzene (which is sometimes referred to as Möbius benzene).

Now comes a report that the PES for opening of Dewar benzene is a bit more complicated.² B3LYP/6-311+G** computations of 1 going to 3 identifies not only the Möat;bius benzene intermediate 2 but a transition state connecting 1 to 2 and a second transition state that connects 2 with 3. These structures are shown in Figure 1.

1	TS1
2	TS2
3

Figure 1. B3LYP/6-311+G** optimized geometries of 1-3 and the two TSs.²

The first TS is 31.0 kcal mol^-1 above reactant and the Möbius benzene intermediate is only 2.1 kcal mol^-1 below this TS. The second TS is 1.6 kcal mol^-1 higher than the first TS, and so is rate-limiting.

The authors also examined a series of related Dewar benzenes and all have two TSs, with the second always higher than the first.

Molecular dynamics computations suggest that the Möbius benzene is likely avoided during the reaction. The fact that the two TSs are similar in energy disguised the fact that there is a second one – the energy of the first TS matches up nicely with experiments. Further MD studies would be interesting to see the interplay between the geometrically quite close intermediate and two TSs – some novel dynamics might be at work here.

References

(1) Johnson, R. P.; Daoust, K. J., "Electrocyclic Ring Opening Modes of Dewar Benzenes: Ab Initio Predictions for Möbius Benzene and trans-Dewar Benzene as New C₆H₆ Isomers," J. Am. Chem. Soc., 1996, 118, 7381-7385, DOI: 10.1021/ja961066q

(2) Dracinsky, M.; Castano, O.; Kotora, M.; Bour, P., "Rearrangement of Dewar Benzene Derivatives Studied by DFT," J. Org. Chem. 2010, ASAP, DOI: 10.1021/jo902065n

InChIs

1: InChI=1/C18H20O2/c1-11-12(2)18(4)15(16(19)20-5)14(17(11,18)3)13-9-7-6-8-10-13/h6-10H,1-5H3
InChIKey=LGAXKHBTTKUURV-UHFFFAOYAH

3: InChI=1/C18H20O2/c1-11-12(2)14(4)17(18(19)20-5)16(13(11)3)15-9-7-6-8-10-15/h6-10H,1-5H3
InChIKey=OUPUSCZNPIJJAH-UHFFFAOYAO

Does the Carbon-Sulfur triple bond exist? There’s probably little doubt it does in the CS molecule. But now Schreiner and Mloston have offered up the H-C≡S-OH species as a possibility.¹ Obtained by flash photolysis of 1, giving 2, and upon irradiation at 254 nm, H-C≡S-OH 3 is the observed species and not the expected carbene HO-C-SH 4. 3 is confirmed by excellent agreement between the observed and computationally predicted IR spectra.

The CCSD(T)/cc-pVTZ structures of 3 and 4 are shown in Figure 1. It is interesting that the carbene is not observed, even though it is 26.6 kcal mol^-1 more stable than 3.

3

4

Figure 1. CCSD(T)/cc-PVTZ optimized structures of 3 and 4.¹

So is there a triple bond? The short C-S distance (1.547 Å) is very similar to that in CS (1.545 Å). NBO analysis indicates a triple bond. But the MOs indicate significant lone pair build-up on both C and S, consistent with the strongly non-linear angles about these two atoms. The authors conclude that 3 is a “structure with a rather strong CS double bond or a weak triple bond”.

References

(1) Schreiner, P. R.; Reisenauer, H. P.; Romanski, J.; Mloston, G., "A Formal Carbon-Sulfur Triple Bond: H-C≡S-O-H," Angew. Chem. Int. Ed., 2009, 48, 8133-8136, DOI: 10.1002/anie.200903969

An emerging theme in this blog is Möbius systems, ones that can be aromatic or antiaromatic. Rzepa has led the way here, especially in examining annulenes with a twisted structure. Along with Schleyer and Schaefer, they have now explored a series of Möbius annulenes.¹ The particularly novel aspect of this new work is the examination of higher-order Möbius systems. In the commonly held notion of the Möbius strip, the strip contains a single half twist. Rzepa points out that the notion of twist must be considered as two parts, a part due to torsions and a part due to writhe.² We can think of the Möbius strip as formed by a ladder where the ends are connect such that the left bottom post connects with the top right post and the bottom right post connects with the top left post. Let’s now consider the circle created by joining the midpoints of each rug of the ladder. If this circle lies in a plane, then the torsion is π/N where N is the number of rungs in the ladder. But, the collection of midpoints does not have to lie in a plane, and if these points distort out of plane, that’s writhe and allows for less torsion in the strip.The sum of these two parts is called L_k and it will be an integral multiple of π. So the common Möbius strip has L_k = 1.

An example of a molecular analogue of the common Möbius strip is the annulene C₉H₉⁺ (1) – see figure 1. But Möbius strips can have more than one twist. Rzepa, Schleyer, and Schaefer have found examples with L_k = 2, 3, or 4. Examples are C₁₄H₁₄ (2) with one full twist (L_k = 2, two half twists), C₁₆H₁₆^2- (3) with three half twists, and C₂₀H₂₀²⁺ (4) with four half twists.

1	2
3	4

Figure 1. Structures of annulenes 1-4.

These annulenes with higher-order twisting, namely 2-4, are aromatic, as determined by a variety of measures. For example, all express negative NICS values, all have positive diagmagnetic exaltations, and all express positive isomerization stabilization energies (which are a measure of aromatic stabilization energy).

References

(1) Wannere, C. S.; Rzepa, H. S.; Rinderspacher, B. C.; Paul, A.; Allan, C. S. M.; Schaefer Iii, H. F.; Schleyer, P. v. R., "The Geometry and Electronic Topology of Higher-Order Charged M&oml;bius Annulenes" J. Phys. Chem. A 2009, ASAP, DOI: 10.1021/jp902176a

(2) Fowler, P. W.; Rzepa, H. S., "Aromaticity rules for cycles with arbitrary numbers of half-twists," Phys. Chem. Chem. Phys. 2006, 8, 1775-1777, DOI: 10.1039/b601655c.

Here’s another fine paper from the Alonso group employing laser ablation molecular beam Fourier transform microwave spectroscopy coupled with computation to discern molecular structure. In this work they examine the low-energy tautomers of guanine.1 The four lowest energy guanine tautomers are shown in Figure 1. (Unfortunately, Alonso does not include the optimized coordinates of these structures in the supporting information – we need to more vigorously police this during the review process!) These tautomers are predicted to be very close in energy (MP2/6-311++G(d,p), and so one might expect to see multiple signals in the microwave originating from all four tautomers. In fact, they discern all four, and the agreement between the computed and experimental rotational constants are excellent (Table 1), especially if one applies a scaling factor of 1.004. Once again, this group shows the power of combined experiment and computations!

Figure 1. Four lowest energy (kcal mol^-1, MP2/6-311++G(d,p)) tautomers of guanine.

Table 1. Experimental and computed rotational constants (MHz) of the four guanine tautomers.

References

(1) Alonso, J. L.; Peña, I.; López, J. C.; Vaquero, V., "Rotational Spectral Signatures of Four Tautomers of Guanine," Angew. Chem. Int. Ed. 2009, 48, 6141-6143, DOI: 10.1002/anie.200901462

InChIs

Guanine: InChI=1/C5H5N5O/c6-5-9-3-2(4(11)10-5)7-1-8-3/h1H,(H4,6,7,8,9,10,11)/f/h8,10H,6H2
InChIKey=UYTPUPDQBNUYGX-GSQBSFCVCX

Conjugated alkenes have played a major role in conceptualizing organic chemistry. Linear and cyclic unbranched conjugated alkenes have been well studied; the latter class comprising the aromatic and antiaromatic annulenes. The cyclic branched conjugate alkenes are known as radialenes and have been subject of some study. But the last category, the linear branched conjugated alkenes have been overlooked. Paddon-Row and Sherburn¹ now report a general synthetic method for preparing these species, which they call dendralenes, see Scheme 1.

Scheme 1. Classes of conjugated alkenes

The dendralenes fall into two groups – those with an odd number of double bonds and those with an even number. While the UV/Vis absorption maximum redshifts with increasing length, the molar extinctions coefficients are relatively constant for the odd denralenes but it increases by about 10,000 within the even dendralene family. The Diels-Alder chemistry is even more distinctive: the odd dendralenes react rapidly with an electron deficient dienophile (N-methylmaleimide), with rates decreasing slightly with increasing size, but the even dendralenes are significantly more sluggish.

The optimized B3LYP/6-31G(d) geometries of the lowest energy conformers of the [3]- to [8]dendralenes are shown in Figure 1. There are three types of butadiene fragments present in these structures: (a) near planar s-trans arrangement, (b) near perpendicular arrangement of the two double bonds, and (c) ­s-cis arrangement with the dihedral angle about 40°. The even dendralenes have only the first two type: alternating planar butadiene fragment that are more-or-less orthogonal to each other. The odd dendralenes all have at least one s-cis arrangement. Paddon-Row and Sherburn suggest that since the s-cis arrangement is necessary for the diene component of the Diels-SAlder reaction, the odd dendralenes are more reactive than the even ones since they have this arranegement in their ground state conformations, while the even dendralenes will have to react out of a higher energy conformation. This is a nice explanation readily formulated from simple computations.

[3]dendralene	[4]dendralene
[5]dendralene	[6]dendralene
[7]dendralene	[8]dendralene

Figure 1. B3LYP/6-31G(d) optimized structures of [3]- to [8]dendralene.¹

References

(1) Payne, A. D.; Bojase, G.; Paddon-Row, M. N.; Sherburn, M. S., "Practical Synthesis of the Dendralene Family Reveals Alternation in Behavior," Angew. Chem. Int. Ed. 2009, 48, 4836-4839, DOI: 10.1002/anie.200901733

InChIs

[3]dendralene: InChI=1/C6H8/c1-4-6(3)5-2/h4-5H,1-3H2
InChIKey=VXBVLYQDVVHAHZ-UHFFFAOYAS

[4]dendralene: InChI=1/C8H10/c1-5-7(3)8(4)6-2/h5-6H,1-4H2
InChIKey=DMCINEDFOKMBFI-UHFFFAOYAV

[5]dendralene: InChI=1/C10H12/c1-6-8(3)10(5)9(4)7-2/h6-7H,1-5H2
InChIKey=XEZCEXNNZGLEHB-UHFFFAOYAM

[6]dendralene: InChI=1/C12H14/c1-7-9(3)11(5)12(6)10(4)8-2/h7-8H,1-6H2
InChIKey=RBABOPLFRQKABD-UHFFFAOYAA

[7]dendralene: InChI=1/C14H16/c1-8-10(3)12(5)14(7)13(6)11(4)9-2/h8-9H,1-7H2
InChIKey=ZIBYAXDRKFGSBF-UHFFFAOYAH

[8]dendralene: InChI=1/C16H18/c1-9-11(3)13(5)15(7)16(8)14(6)12(4)10-2/h9-10H,1-8H2
InChIKey=YWPORNAHEZCVCQ-UHFFFAOYAR

Schaefer, Csaszar, and Allen have applied the focal point method towards predicting the energies and structures of cysteine.¹ This very high level method refines the structures that can be used to compare against those observed by Alonso² in his laser ablation molecular beam Fourier transform microwave spectroscopy experiment (see this post). They performed a broad conformation search, initially examining some 66,664 structures. These reduced to 71 unique conformations at MP2/cc-pvTZ. The lowest 11 energy structures were further optimized at MP2(FC)/aug-cc-pV(T+d)Z. The four lowest energy conformations are shown in Figure 1 along with their relative energies.

I (0.0)	II (4.79)
III (5.81)	IV (5.95)

Figure 1. MP2(FC)/aug-cc-pV(T+d)Z optimized geometries and focal point relative energies (kJ mol^-1) of the four lowest energy conformers of cysteine.¹

The three lowest energy structures found here match up with the lowest two structures found by Alonso and the energy differences are also quite comparable: 4.79 kJ and 5.81 mol^-1 with the focal point method 3.89 and 5.38 kJ mol^-1 with MP4/6-311++G(d,p)// MP2/6-311++G(d,p). So the identification of the cysteine conformers made by Alonso remains on firm ground.

References

(1) Wilke, J. J.; Lind, M. C.; Schaefer, H. F.; Csaszar, A. G.; Allen, W. D., "Conformers of Gaseous Cysteine," J. Chem. Theory Comput. 2009, DOI: 10.1021/ct900005c.

(2) Sanz, M. E.; Blanco, S.; López, J. C.; Alonso, J. L., "Rotational Probes of Six Conformers of Neutral Cysteine," Angew. Chem. Int. Ed. 2008, 4, 6216-6220, DOI: 10.1002/anie.200801337

InChIs

Cysteine:
InChI=1/C3H7NO2S/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1
InChIKey: XUJNEKJLAYXESH-REOHCLBHBU