IChO 2021 · Theory problem 8

Dynamic Organic Molecules and Their Chirality

Download PDFIChO 2021

PART A

Polycyclic aromatic hydrocarbons with successive ortho-connections are called [n]carbohelicenes (here, n represents the number of six-membered rings) (see below). [4]Carbohelicene ([4]C) is efficiently prepared by a route using a photoreaction as shown below, via an intermediate (Int.) that is readily oxidized by iodine.

Figure 1

The photoreaction proceeds in a manner similar to the following example.

Figure 2

Note: For all of Question 8, please draw alternating single and double bonds in your answers to the problems as depicted in the examples of carbohelicene. Do not use circles for conjugated \(\pi\) systems.

8.1 Draw the structures of A–C. Stereoisomers should be distinguished.

8.2 Attempts to synthesize [5]carbohelicene from the same phosphonium salt and an appropriate starting compound resulted in the formation of only a trace amount of [5]carbohelicene, instead affording product D whose molecular weight was 2 Da lower than that of [5]carbohelicene. The \({}^{1}\mathrm H\) NMR chemical shifts of D are listed below. Draw the structure of D. [D (\(\delta\), ppm in \(\ce{CS2}\), r.t.), 8.85 (2H), 8.23 (2H), 8.07 (2H), 8.01 (2H), 7.97 (2H), 7.91 (2H)]

[5]- and larger [n]carbohelicenes have helical chirality and interconversion between enantiomers of these helicenes is significantly slow at room temperature. The chirality of [n]carbohelicenes is defined as \((M)\) or \((P)\) as shown below.

Figure 3

[n]Carbohelicenes with n larger than 4 can be enantiomerically separated by a chiral column chromatography, which was developed by Prof. Yoshio Okamoto.

Figure 4

Photo courtesy: The Japan Prize Foundation

Multiple helicenes are molecules that contain two or more helicene-like structures. If its helical chirality is considered, several stereoisomers exist in a multiple helicene. For example, compound E contains three [5]carbohelicene-like moieties in one molecule. One of the stereoisomers is described as \((P,P,P)\) as shown below.

Figure 5

8.3 The nickel-mediated trimerization of 1,2-dibromobenzene generates triphenylene. When the same reaction is applied to an enantiomer of F, \((P)\)-F, multiple helicene G (\(\ce{C66H36}\)) is obtained. Given that interconversion between stereoisomers does not occur during the reaction, identify all the possible stereoisomers of G formed in this process, without duplication. As a reference, one isomer should be drawn completely with the chirality defined as in the example above, with numerical labels; the other stereoisomers should be listed with location numbers and \(M\) and \(P\) labels according to the same numbering. For instance, the other stereoisomers of E should be listed as \((1,2,3)=(P,M,P)\), \((P,M,M)\), \((P,P,M)\), \((M,M,M)\), \((M,M,P)\), \((M,P,P)\), and \((M,P,M)\).

Figure 6
Figure 7

PART B

Sumanene is a bowl-shaped hydrocarbon that was first reported in Japan in 2003. The name "sumanene" derives from a Sanskrit-Hindi word "suman" that means sunflower. The synthesis of sumanene was achieved by a reaction sequence that consists of a ring-opening and a ring-closing metathesis.

Figure 8

Representative metathesis reactions catalyzed by a ruthenium catalyst (\(\mathrm{Ru^*}\)) are shown below.

Figure 9
Figure 10

8.4 Draw the structure of intermediate I (its stereochemistry is not required).

Figure 11

8.5 Starting from the optically active precursor J, the same reaction sequence gives the optically active sumanene derivative K. The stereocenters in J suffer no inversion during the metathesis reaction. Draw the structure of K with the appropriate stereochemistry.

Official English text of the problem.

Answers

All SMILES below use explicit Kekulé single and double bonds. Ordinary SMILES does not encode helicene handedness or bowl chirality; the accompanying spatial descriptions specify those configurations.

  • 8.1

A: Naphthalene-2-carbaldehyde, O=CC1=CC2=CC=CC=C2C=C1.

B: \((E)\)-2-Styrylnaphthalene, C1=CC=CC=C1/C=C/C1=CC2=CC=CC=C2C=C1.

C: \((Z)\)-2-Styrylnaphthalene, C1=CC=CC=C1/C=C\C1=CC2=CC=CC=C2C=C1.

  • 8.2 D: Benzo[ghi]perylene, \(\ce{C22H12}\), C1=CC2=CC=C3C=CC4=C5C6=C(C=CC=C6C(=C1)C2=C35)C=C4.

  • 8.3 G: A hexapole [5]carbohelicene, \(\ce{C66H36}\), with constitutional SMILES
    C1=CC=C2C(=C1)C=CC1=C2C2=C3C=CC=CC3=CC=C2C2=C3C4=CC=C5C=CC=CC5=C4C4=C5C=CC=CC5=CC=C4C3=C3C4=CC=C5C=CC=CC5=C4C4=C5C=CC=CC5=CC=C4C3=C12.

Number its helicenes consecutively around the molecule, with 1, 3, 5 inherited from the three molecules of \((P)\)-F, and 2, 4, 6 newly formed between neighboring units. There are four distinct products: \[ \begin{aligned} (1,2,3,4,5,6)={}&(P,P,P,P,P,P),\\ &(P,P,P,P,P,M),\\ &(P,P,P,M,P,M),\\ &(P,M,P,M,P,M). \end{aligned} \]

  • 8.4 I: Hexahydrosumanene, \(\ce{C21H18}\), C1=CC2CC3C=CC4CC5C=CC6CC1C1=C2C3=C4C5=C16.

It has the sumanene carbon skeleton, a central benzene ring, three methylene bridges, six saturated ring-junction \(\ce{CH}\) groups, and one outer \(\ce{C=C}\) bond in each peripheral six-membered ring.

  • 8.5 K: The specified bowl enantiomer of \(C_3\)-symmetric trimethylsumanene, \(\ce{C24H18}\), with constitutional SMILES
    CC1=CC2=C3C4=C1CC1=C4C4=C(CC5=C4C3=C(C2)C(C)=C5)C(C)=C1.

Precise drawing: Look into the concave face of the bowl, with one peripheral benzene ring at the top. Put a methyl group on that ring’s upper-right outer carbon, and obtain the other two methyl positions by successive \(120^\circ\) rotations. The three methylene rim vertices project toward the viewer relative to the central benzene.

Solution

8.1 — Identifying the aldehyde and the two alkene geometries

The phosphonium salt and sodium ethoxide constitute a Wittig reaction system. They convert an aldehyde group into a phenyl-substituted alkene:

\[ \ce{C11H8O + [Ph3PCH2Ph]Br + NaOEt -> C18H14 + Ph3PO + NaBr + EtOH}. \]

The \(\ce{C18H14}\) product denotes the mixture of B and C, rather than two equivalents of product.

The species in this balance are benzyltriphenylphosphonium bromide, [Br-].[P+](CC1=CC=CC=C1)(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1; sodium ethoxide, [Na+].CC[O-]; triphenylphosphine oxide, O=P(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1; sodium bromide, [Na+].[Br-]; and ethanol, CCO.

Working backward from the illustrated four-ring product identifies the aromatic fragment as 2-naphthyl. The newly formed ring joins naphthalene C1 to an ortho carbon of the phenyl ring; the original vinyl substituent is therefore at naphthalene C2. Thus A is naphthalene-2-carbaldehyde.

The two Wittig products differ in alkene geometry:

  • In B, the naphthyl and phenyl groups are opposite across the double bond: \(E\).
  • In C, they are on the same side: \(Z\).

Light interconverts these geometries. The \(Z\) isomer can adopt the geometry needed for a six-electron electrocyclic closure. The photochemical closure is conrotatory and produces the illustrated dihydro intermediate without changing its formula:

\[ \ce{C18H14 ->[h\nu] C18H14}. \]

Here the reactant is C, and the product is dihydro[4]carbohelicene Int., with constitutional SMILES C1=CC2=CC=C3C=CC4=CC=CC=C4C3C2C=C1.

Oxidation removes the two hydrogens at the newly connected carbons and restores the aromatic system:

\[ \ce{C18H14 + I2 -> C18H12 + 2HI}. \]

Iodine is II; hydrogen iodide is [H]I. The product is [4]carbohelicene, also called benzo[c]phenanthrene, C1=CC=C2C(=C1)C=CC1=C2C2=CC=CC=C2C=C1.

8.2 — Identifying the additional oxidative cyclization product

An unmodified [n]carbohelicene has formula

\[ \ce{C_{4n+2}H_{2n+4}}. \]

Consequently, [5]carbohelicene—pentahelicene, C1=CC=C2C(=C1)C=CC1=C2C2=C(C=CC3=CC=CC=C32)C=C1—has formula \(\ce{C22H14}\).

A product lower in molecular mass by approximately \(2\ \mathrm{Da}\), with the same carbon skeleton, corresponds to loss of two hydrogen atoms:

\[ \ce{C22H14 -> C22H12}. \]

The hydrogen count is independently supported by the NMR integrations:

\[ 6\times 2\mathrm H=12\mathrm H. \]

The degrees of unsaturation are

\[ \operatorname{DBE}(\ce{C22H14}) =\frac{2(22)+2-14}{2}=16, \] \[ \operatorname{DBE}(\ce{C22H12}) =\frac{2(22)+2-12}{2}=17. \]

Thus one additional ring can form through a new carbon–carbon bond between the closely approaching terminal regions of the five-ring helicene, followed by oxidative loss of two hydrogens. This produces benzo[ghi]perylene D, a planar, six-ring aromatic hydrocarbon.

The formal iodine-mediated oxidative balance is

\[ \ce{C22H14 + I2 -> C22H12 + 2HI}. \]

Drawing description: Begin with [5]carbohelicene and connect the two inward-facing terminal carbons that close its remaining central six-membered bay. Remove their hydrogens and draw a valid Kekulé pattern.

The resulting structure has six symmetry-related pairs of proton-bearing carbons, consistent with the six reported resonances, each integrating to two hydrogens. Individual assignment of the six chemical shifts is unnecessary for identifying D.

8.3 — Constructing G and removing duplicate stereoisomers

The nickel-mediated reaction joins the six bromine-bearing carbon atoms of three starting molecules into a central benzene ring. A formal balance, omitting the ligands, is

\[ \ce{3C22H12Br2 + 3Ni -> C66H36 + 3NiBr2}. \]

Nickel(0) is [Ni]; nickel(II) bromide is [Ni+2].[Br-].[Br-].

The starting compound is the depicted dibromo[5]carbohelicene F, with constitutional SMILES BrC1=C(Br)C2=C(C3=CC=CC=C3C=C2)C2=C1C=CC1=CC=CC=C12; its helicity is explicitly \(P\).

The construction parallels formation of triphenylene, C1=CC=C2C(=C1)C1=CC=CC=C1C1=CC=CC=C21, but each of its three outer fused rings now carries the remaining four rings of a starting helicene.

Complete reference-structure description: Draw a central benzene ring. Fuse the middle ring of each of three [5]carbohelicene units to alternate edges of this central ring, using the former bromine-bearing edge of each unit. This gives the connectivity specified by the SMILES for G. The product contains six [5]helicene substructures.

Call the three starting units \(X_1,X_2,X_3\), in clockwise order, and number the helicenes as follows:

Label Helical substructure
1 Original helicene within \(X_1\)
2 Newly formed helicene between \(X_1\) and \(X_2\)
3 Original helicene within \(X_2\)
4 Newly formed helicene between \(X_2\) and \(X_3\)
5 Original helicene within \(X_3\)
6 Newly formed helicene between \(X_3\) and \(X_1\)

For the reference drawing, mark all six helicenes \(P\): each is a right-handed helix.

Because inversion does not occur, helicenes 1, 3, 5 remain \(P\). Each of the three new helicenes may be \(P\) or \(M\), giving \(2^3=8\) labeled possibilities.

However, cyclic rotation of the three identical starting units makes several labeled assignments equivalent. The distinct classes contain:

  1. No new \(M\) helices.
  2. One new \(M\) helix.
  3. Two new \(M\) helices.
  4. Three new \(M\) helices.

Equivalently, counting configurations under the threefold rotation gives

\[ N=\frac{8+2+2}{3}=\boxed{4}. \]

These are exactly the four configurations listed in Answers.

8.4 — Following the metathesis rearrangement

The ruthenium-catalyzed sequence changes connectivity while conserving the molecular formula:

\[ \underbrace{\ce{C21H18}}_{\mathrm H} \xrightarrow{\mathrm{Ru^*}} \underbrace{\ce{C21H18}}_{\mathrm I}. \]

Each original bicyclic unit contains a methylene bridge and an outer alkene. Ring-opening metathesis breaks the original outer alkene connections; ring-closing metathesis reconnects neighboring units.

More explicitly, label the three original outer double bonds \(p_i=q_i\), with \(i=1,2,3\) in clockwise order. The rearrangement replaces them with \(q_i=p_{i+1}\), taking indices modulo three. The three methylene bridges are retained and become the methylene vertices of the three five-membered rings.

This produces hexahydrosumanene I.

Drawing description: Start with the sumanene skeleton shown in the question. Keep the central benzene ring and all three methylene vertices. In each peripheral six-membered ring:

  • Make its two junction carbons adjoining the neighboring pentagons saturated \(\ce{CH}\) groups.
  • Retain a double bond between its two outer, nonfused carbon atoms.

A Kekulé drawing can therefore show each peripheral six-membered ring as a substituted cyclohexa-1,4-diene unit.

The hydrogen count verifies the proposed intermediate:

\[ 3(\ce{CH2})+6(\text{saturated }\ce{CH}) +6(\text{alkenic }\ce{CH}) \quad\Rightarrow\quad \ce{C21H18}, \]

including the six hydrogen-free carbons of the central benzene ring.

The oxidant is DDQ, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O. Each molecule accepts two hydrogen atoms. Aromatization of all three peripheral rings therefore requires three equivalents:

\[ \ce{C21H18 + 3C8Cl2N2O2 -> C21H12 + 3C8H2Cl2N2O2}. \]

The hydrocarbon product is sumanene, C1=CC2=C3C4=C1CC1=C4C4=C(C=C1)CC1=C4C3=C(C=C1)C2.

The reduced oxidant is 2,3-dichloro-5,6-dicyanobenzene-1,4-diol, N#CC1=C(C#N)C(O)=C(Cl)C(Cl)=C1O.

8.5 — Tracking the methyl groups and bowl handedness

In J, each methyl group is attached to an outer alkene carbon. Consequently, the methyl groups remain attached to carbons that become part of the three peripheral aromatic rings.

For an explicit stereochemical reference, the drawn trimethylated bridged precursor J has isomeric SMILES:

CC1=C[C@@H]2C[C@H]1C1=C2C2=C(C3=C1[C@@H]1C=C(C)[C@H]3C1)[C@@H]1C=C(C)[C@H]2C1.

The formula changes are

\[ \underbrace{\ce{C24H24}}_{\mathrm J} \xrightarrow{\mathrm{Ru^*}} \underbrace{\ce{C24H24}}_{\text{rearranged intermediate}}, \]

followed by

\[ \ce{C24H24 + 3C8Cl2N2O2 -> C24H18 + 3C8H2Cl2N2O2}. \]

The final formula also follows directly from replacing three aromatic hydrogens of sumanene by methyl groups:

\[ \ce{C21H12}+3(\ce{CH3}-\ce{H}) \quad\Rightarrow\quad \ce{C24H18}. \]

To determine the enantiomer, retain the configurations of all six original bridgeheads during the metathesis bond reconnections. In the upper bicyclic unit of the supplied drawing, the methyl-bearing alkene carbon is attached to the upper-right bridgehead. Tracking this carbon through the neighboring-ring closure gives the following equivalent projections of K:

  • Viewed from the convex face: with one peripheral benzene at the top, its methyl is at the upper-left outer carbon.
  • Viewed into the concave face: the same methyl is at the upper-right outer carbon.

The other two methyl groups follow by \(120^\circ\) rotations. This specifies the bowl enantiomer obtained from the drawn J.

Oxidation converts the six retained bridgehead stereocenters into trigonal aromatic carbons. The final chirality resides in the bowl together with its directional threefold methyl-substitution pattern; it is therefore specified by the spatial description rather than by tetrahedral @ symbols in the SMILES for K.

The answers were checked against the official answers published by the organisers.