Chapter: Stereoselectivity in Cyclic Molecules

1. Introduction to Stereoisomerism in Cyclic Systems

• Stereoisomers: Compounds that have the same molecular formula and connectivity but differ in the spatial arrangement of their atoms.
• Significance in Cyclic Molecules: The cyclic nature of these compounds imposes significant restrictions on bond rotation, which in turn leads to unique types of stereoisomers not typically found in open-chain (acyclic) molecules. The rigidity of the ring system means that groups attached to the ring carbons can be on the same side or opposite sides of the ring plane, leading to distinct isomers.
• Stereoselective Processes: Refers to reactions where one stereoisomer is formed in preference to others. While this chapter focuses on the nature of stereoisomers in cyclic molecules, understanding their existence is foundational to studying stereoselective reactions.

2. Cis/Trans Isomerism in Cycloalkanes

• Definition: For disubstituted (or polysubstituted) cycloalkanes, two substituents can be on the same side of the ring plane (designated as cis isomer) or on opposite sides of the ring plane (designated as trans isomer).
• Key Characteristic: Cis and trans isomers are a type of diastereomer (stereoisomers that are not mirror images of each other). They are not interconvertible by simple bond rotation; breaking and reforming bonds would be required to interconvert them.
• Nomenclature:
  • Prefix “cis-” or “trans-” is used.
  • Substituent positions are indicated by numbers (e.g., 1,2-dimethylcyclopropane).
• Examples:
  • 1,2-Dimethylcyclopropane:
    • cis-1,2-dimethylcyclopropane: Both methyl groups on the same side of the ring. It is an achiral molecule (often a meso compound).
    • trans-1,2-dimethylcyclopropane: Methyl groups on opposite sides. It exists as a pair of enantiomers (chiral).
  • 1,2-Dimethylcyclopentane:
    • cis-1,2-dimethylcyclopentane: Methyl groups on the same side. It is a chiral molecule (exists as enantiomers due to non-superimposable mirror images).
    • trans-1,2-dimethylcyclopentane: Methyl groups on opposite sides. It is also a chiral molecule (exists as enantiomers).
  • 1,3-Dimethylcyclopentane:
    • cis-1,3-dimethylcyclopentane: Methyl groups on the same side. Chiral.
    • trans-1,3-dimethylcyclopentane: Methyl groups on opposite sides. Achiral (meso compound).
  • 1,4-Dimethylcyclohexane:
    • cis-1,4-dimethylcyclohexane: Methyl groups on the same side. Achiral.
    • trans-1,4-dimethylcyclohexane: Methyl groups on opposite sides. Achiral. (Note: These are often viewed in their preferred chair conformations which are often diequatorial or axial/equatorial depending on cis/trans and substitution pattern).

3. Chirality in Cyclic Molecules

• Review of Chiral Centers: A carbon atom that is bonded to four different groups. Cyclic molecules can contain chiral centers within the ring.
• Overall Chirality of the Molecule: A molecule is chiral if it is non-superimposable on its mirror image. The presence of chiral centers is a strong indicator of chirality, but not a guarantee (e.g., meso compounds). Conversely, a molecule without chiral centers can still be chiral (e.g., atropisomers in biphenyls, though less relevant for simple cycloalkanes).
• Absence of Symmetry Elements: The key criteria for a molecule to be chiral is the absence of:
  • Plane of Symmetry (σ): An imaginary plane that divides the molecule into two halves that are mirror images of each other.
  • Center of Inversion (i): A point within the molecule such that any line drawn from an atom through this point connects to an identical atom equidistant on the opposite side.
  • Alternating Axis of Symmetry (Sn​): A more complex symmetry element.
• Enantiomers: Stereoisomers that are non-superimposable mirror images of each other. They must be chiral molecules.
• Diastereomers: Stereoisomers that are not mirror images of each other. Cis/trans isomers are common examples of diastereomers. Meso compounds are also diastereomers of their chiral stereoisomers.

4. Meso Compounds in Cyclic Systems

• Definition: A meso compound is an achiral compound that possesses two or more chiral centers. Its achirality arises from the presence of an internal plane of symmetry or a center of inversion, which makes the molecule superimposable on its mirror image.
• Key Features:
  • Contains chiral centers.
  • Is optically inactive (does not rotate plane-polarized light).
  • Has an internal plane of symmetry or a center of inversion.
• Examples in Cyclic Systems:
  • cis-1,2-dimethylcyclopropane: Has two chiral centers but a plane of symmetry passing through the midpoints of the C-C bond between the two substituted carbons and the opposite C atom, bisecting the two methyl groups.
  • trans-1,3-dimethylcyclobutane: This one is actually chiral.
  • cis-1,3-dimethylcyclobutane: Achiral due to a plane of symmetry.
  • cis-1,3-dimethylcyclohexane: Achiral (meso) in its most stable conformation (diequatorial). A plane of symmetry passes through C2​ and C5​ and the midpoints of the C1​−C6​ and C3​−C4​ bonds.
  • cis-1,2-cyclopentanediol: Can be a meso compound if the molecule can adopt a conformation that possesses a plane of symmetry (e.g., envelope with the plane bisecting the two OHs and carbons and the opposite carbon).
• Distinguishing Chiral from Meso: Always check for internal symmetry elements, even if chiral centers are present. Ring puckering can sometimes obscure obvious planes of symmetry; careful consideration of all possible conformations is sometimes necessary (e.g., for 1,2-disubstituted cyclopentanes, the cis isomer is actually chiral because its puckered conformations break the plane of symmetry).

5. Relationship between Conformation and Stereoisomerism in Cyclohexanes

• Review of Chair Conformation: Recall the axial and equatorial positions in cyclohexane.
• Translating Cis/Trans to Axial/Equatorial:
  • 1,2-Disubstituted Cyclohexanes:
    • cis-1,2: Always one substituent axial and the other equatorial (a,e or e,a). Both chair forms are equivalent in energy if the substituents are identical.
    • trans-1,2: Can be both axial (a,a) or both equatorial (e,e). The diequatorial (e,e) conformation is significantly more stable due to reduced 1,3-diaxial interactions and torsional strain.
  • 1,3-Disubstituted Cyclohexanes:
    • cis-1,3: Can be both axial (a,a) or both equatorial (e,e). The diequatorial (e,e) conformation is more stable. This is a common example of a meso compound if substituents are identical.
    • trans-1,3: Always one axial and one equatorial (a,e or e,a).
  • 1,4-Disubstituted Cyclohexanes:
    • cis-1,4: Always one axial and one equatorial (a,e or e,a). This is often an achiral molecule.
    • trans-1,4: Can be both axial (a,a) or both equatorial (e,e). The diequatorial (e,e) conformation is significantly more stable.
• Relative Stability of Cis/Trans Isomers:
  • For disubstituted cyclohexanes with identical substituents, the trans isomer is generally more stable than the cis isomer if the trans isomer can adopt a diequatorial conformation (e.g., trans-1,2-dimethylcyclohexane, trans-1,4-dimethylcyclohexane).
  • Conversely, for 1,3-disubstituted cyclohexanes with identical groups, the cis isomer can be diequatorial and is therefore more stable than the trans isomer (which would be axial-equatorial).
  • The overall stability of an isomer is determined by the stability of its most favored conformation.

6. Drawing Conventions for Cyclic Stereoisomers

• Wedge and Dash Notation:
  • Wedge bonds (▲): Indicate that the substituent is coming out of the plane of the paper, towards the viewer.
  • Dash bonds (⋯): Indicate that the substituent is going behind the plane of the paper, away from the viewer.
  • Groups on the same side of the ring are both wedges or both dashes (cis). Groups on opposite sides are one wedge and one dash (trans).
• Chair Conformations:
  • Used specifically for cyclohexanes.
  • Axial bonds: Drawn vertical (straight up or straight down).
  • Equatorial bonds: Drawn roughly horizontal, slightly angled to avoid eclipsing the adjacent axial bond, and pointing away from the ring axis.
  • Remember the ring flip interconverts axial and equatorial positions while maintaining the “up” or “down” orientation of the substituent relative to the ring plane.

7. Stereoselectivity in Reactions (Brief Mention)

• While this chapter focuses on the nature of stereoisomers, it’s important to note that many reactions involving cyclic molecules exhibit stereoselectivity. This means that when a reaction could potentially form multiple stereoisomers (e.g., cis and trans, or different enantiomers), one stereoisomer is formed preferentially over the others. This preference often arises from the inherent geometry of the cyclic reactants and/or the mechanism of the reaction.

Multiple Choice Questions (MCQ) on Stereoselectivity in Cyclic Molecules

Instructions: Choose the best answer for each question.

1. What is the defining characteristic that differentiates stereoisomers from constitutional isomers? a) Different molecular formulas. b) Different connectivity of atoms. c) Same connectivity, but different spatial arrangement of atoms. d) Different number of double bonds.

2. Why do cyclic molecules often exhibit unique types of stereoisomerism compared to acyclic molecules? a) They have higher boiling points. b) They possess restricted rotation around single bonds due to the ring structure. c) They always contain chiral centers. d) They are more reactive.

3. In a disubstituted cycloalkane, what does the “cis” prefix indicate about the substituents? a) They are on opposite sides of the ring. b) They are on the same side of the ring. c) They are axial. d) They are equatorial.

4. What type of stereoisomers are cis and trans isomers of a cyclic compound? a) Enantiomers b) Constitutional isomers c) Diastereomers d) Conformational isomers

5. Which of the following is true regarding the interconversion of cis and trans isomers of a cyclic compound? a) They can interconvert by simple bond rotation at room temperature. b) They require breaking and reforming covalent bonds to interconvert. c) They are in rapid equilibrium with each other. d) They are indistinguishable by NMR spectroscopy.

6. Which statement accurately describes trans-1,2-dimethylcyclopropane? a) It is an achiral meso compound. b) It exists as a pair of enantiomers. c) It is superimposable on its mirror image. d) It is more stable than the cis isomer due to less steric strain.

7. A molecule is considered chiral if it lacks which of the following symmetry elements? a) A rotational axis. b) A plane of symmetry. c) A center of inversion. d) Both b and c.

8. How many chiral centers are present in cis-1,2-dimethylcyclopropane? a) 0 b) 1 c) 2 d) 3

9. What is a “meso compound”? a) A chiral compound with multiple chiral centers. b) An achiral compound that possesses two or more chiral centers and an internal plane of symmetry. c) A compound with no chiral centers but exhibiting optical activity. d) A compound that is superimposable on its mirror image but lacks chiral centers.

10. Which of the following is an example of a meso compound? a) trans-1,2-dimethylcyclopropane b) cis-1,2-dimethylcyclopropane c) (R)-1,2-dichlorocyclohexane d) (S)-2-butanol

11. Which symmetry element is typically responsible for a meso compound being achiral despite having chiral centers? a) An axis of rotation. b) A plane of symmetry. c) A center of inversion. d) Both b and c.

12. In the chair conformation of cyclohexane, how are axial bonds oriented? a) Roughly horizontal and pointing outwards. b) Parallel to the average plane of the ring. c) Perpendicular to the average plane of the ring (straight up or straight down). d) At a 45∘ angle to the ring plane.

13. During a cyclohexane ring flip, what happens to an equatorial substituent that was pointing “up” relative to the ring? a) It becomes axial and points “down”. b) It becomes axial and still points “up”. c) It remains equatorial and points “up”. d) It is converted into a different chemical group.

14. In cis-1,2-dimethylcyclohexane, what are the axial/equatorial orientations of the methyl groups in its chair conformations? a) Both axial or both equatorial. b) One axial, one equatorial. c) Both methyl groups are removed due to steric hindrance. d) Only boat conformations exist.

15. Which conformation is generally more stable for trans-1,2-dimethylcyclohexane? a) Both methyl groups axial (a,a). b) Both methyl groups equatorial (e,e). c) One axial, one equatorial (a,e). d) The boat conformation.

16. For 1,3-disubstituted cyclohexanes with identical substituents, which isomer is typically more stable? a) The cis isomer (diequatorial). b) The trans isomer (axial-equatorial). c) Both are equally stable. d) It depends on the size of the substituents.

17. What is the primary reason why a substituent prefers the equatorial position in a monosubstituted cyclohexane? a) To avoid torsional strain. b) To avoid angle strain. c) To minimize 1,3-diaxial interactions. d) To maximize hydrogen bonding.

18. What is the relationship between cis-1,4-dimethylcyclohexane and trans-1,4-dimethylcyclohexane? a) They are enantiomers. b) They are constitutional isomers. c) They are diastereomers. d) They are conformational isomers.

19. A molecule with two chiral centers is definitively chiral if it: a) Has a plane of symmetry. b) Is optically inactive. c) Is non-superimposable on its mirror image. d) Has a center of inversion.

20. Which of the following statements about cis-1,3-dimethylcyclohexane is correct? a) It is a chiral compound. b) It can exist in a chair conformation where both methyl groups are equatorial. c) It is less stable than trans-1,3-dimethylcyclohexane. d) It is optically active.

21. In a wedge and dash drawing of a cyclic molecule, if two substituents are drawn with one wedge bond and one dash bond, they are in a: a) Cis relationship. b) Trans relationship. c) Equatorial relationship. d) Axial relationship.

22. Which of the following disubstituted cyclopentanes is achiral (meso)? a) cis-1,2-dimethylcyclopentane b) trans-1,2-dimethylcyclopentane c) trans-1,3-dimethylcyclopentane d) cis-1,3-dimethylcyclopentane

23. How many distinct stereoisomers (including enantiomers and meso compounds) are possible for 1,2-dichlorocyclopropane? a) 1 b) 2 c) 3 d) 4

24. Which of the following elements of symmetry would make a molecule achiral if present? a) C2​ rotational axis b) Plane of symmetry (σ) c) Cn​ rotational axis d) None of the above; only chiral centers determine chirality.

25. When drawing a cyclohexane chair conformation, an equatorial bond on a carbon pointing “up” is drawn: a) Straight up. b) Straight down. c) Angled upwards and outwards. d) Angled downwards and outwards.

26. Which of the following best describes the relationship between the two chair conformations of cis-1,2-dimethylcyclohexane? a) They are identical. b) They are enantiomers. c) They are conformational diastereomers. d) They are different, but equivalent in energy.

27. What is the most stable conformation for trans-1-tert-butyl-4-methylcyclohexane? a) Tert-butyl axial, methyl axial. b) Tert-butyl equatorial, methyl equatorial. c) Tert-butyl axial, methyl equatorial. d) Tert-butyl equatorial, methyl axial.

28. If a cyclic compound has one chiral center, it is always: a) A meso compound. b) Optically inactive. c) Chiral. d) A constitutional isomer.

29. Which of the following bicyclic systems often demonstrates cis/trans isomerism at the ring fusion? a) Cyclopropane b) Cyclobutane c) Decalin d) Benzene

30. Why is trans-decalin more stable than cis-decalin? a) Trans-decalin has greater angle strain. b) Trans-decalin is planar. c) Trans-decalin allows both fused rings to adopt strain-minimized chair-like conformations with fewer steric interactions. d) Cis-decalin has only one bridgehead hydrogen.

31. In a disubstituted cyclohexane where the substituents are on adjacent carbons (1,2-disubstituted), a trans relationship implies which of the following preferred axial/equatorial orientations? a) One axial, one equatorial. b) Both axial. c) Both equatorial. d) Both b and c, with ‘c’ being more stable.

32. Consider 1,3-cyclohexanediol. Which isomer (cis or trans) has the potential to be a meso compound? a) Cis b) Trans c) Both cis and trans d) Neither

33. If a molecule has a center of inversion, it is necessarily: a) Chiral. b) Optically active. c) Achiral. d) A meso compound (unless it lacks chiral centers).

34. Which drawing convention is most useful for depicting the relative spatial orientation of substituents around a ring system in a simplified 2D representation? a) Newman projection b) Fischer projection c) Wedge and dash notation d) Sawhorse projection

35. A molecule that is non-superimposable on its mirror image is called a(n): a) Diastereomer b) Enantiomer c) Constitutional isomer d) Tautomer

36. For 1,4-disubstituted cyclohexanes with identical substituents, the trans isomer is generally: a) Less stable than the cis isomer. b) Equally stable to the cis isomer. c) More stable than the cis isomer because it can be diequatorial. d) Optically active.

37. Which of the following disubstituted cyclobutanes is chiral? a) cis-1,3-dichlorocyclobutane b) trans-1,3-dichlorocyclobutane c) cis-1,2-dichlorocyclobutane d) trans-1,2-dichlorocyclobutane

38. The energy difference that arises from the steric repulsion between a substituent in an axial position and the axial hydrogens at C-3 and C-5 is called: a) Torsional strain b) Angle strain c) 1,3-diaxial interaction d) Flagpole interaction

39. When considering the chirality of cyclic molecules, why is it important to consider all possible conformations? a) To determine if cis/trans isomerism is present. b) Because a molecule that is chiral in one conformation might be achiral in another. c) Because a molecule might possess a plane of symmetry only in a particular conformation, rendering it meso. d) To evaluate the A-value of its substituents.

40. A stereoselective reaction is one where: a) Only one stereoisomer is formed. b) Reactants must be chiral. c) One stereoisomer is formed preferentially over others. d) All possible stereoisomers are formed in equal amounts.

Answer Key with Explanations

1. c) Same connectivity, but different spatial arrangement of atoms.
   • Explanation: Stereoisomers have the same atoms connected in the same order, but their arrangement in three-dimensional space differs. Constitutional isomers have different connectivity.
2. b) They possess restricted rotation around single bonds due to the ring structure.
   • Explanation: The cyclic structure prevents free rotation around C-C single bonds within the ring, locking substituents into fixed positions relative to the ring plane and leading to cis/trans isomerism.
3. b) They are on the same side of the ring.
   • Explanation: The “cis” prefix indicates that two substituents are located on the same face (or side) of the ring.
4. c) Diastereomers.
   • Explanation: Cis and trans isomers are stereoisomers that are not mirror images of each other, which is the definition of diastereomers.
5. b) They require breaking and reforming covalent bonds to interconvert.
   • Explanation: The ring structure prevents interconversion by simple bond rotation. To change a cis isomer to a trans isomer (or vice-versa), bonds within the ring must be broken and reformed.
6. b) It exists as a pair of enantiomers.
   • Explanation: trans-1,2-dimethylcyclopropane has two chiral centers and no internal plane of symmetry or center of inversion, making it a chiral molecule that exists as two enantiomers. The cis isomer is meso.
7. d) Both b and c.
   • Explanation: A molecule is chiral (and thus optically active) if and only if it is non-superimposable on its mirror image. This means it cannot possess any plane of symmetry (σ) or center of inversion (i).
8. c) 2.
   • Explanation: Both carbons to which the methyl groups are attached are chiral centers, as they are each bonded to four different groups (methyl, H, and the two different parts of the cyclopropane ring).
9. b) An achiral compound that possesses two or more chiral centers and an internal plane of symmetry.
   • Explanation: This is the definition of a meso compound. They have the potential for chirality due to chiral centers but are rendered achiral by internal symmetry.
10. b) cis-1,2-dimethylcyclopropane.
    • Explanation: While cis-1,2-dimethylcyclopropane has two chiral centers, it also possesses an internal plane of symmetry, making it superimposable on its mirror image and thus achiral (meso).
11. b) A plane of symmetry.
    • Explanation: The presence of an internal plane of symmetry is the most common reason a molecule with chiral centers becomes achiral (meso). A center of inversion can also lead to achirality.
12. c) Perpendicular to the average plane of the ring (straight up or straight down).
    • Explanation: Axial bonds are drawn vertically, either straight up or straight down, parallel to the main axis of the cyclohexane ring.
13. b) It becomes axial and still points “up”.
    • Explanation: During a ring flip, axial positions become equatorial, and equatorial positions become axial. However, the relative orientation of the substituent (whether it points generally “up” or “down” relative to the ring’s overall plane) remains unchanged.
14. b) One axial, one equatorial.
    • Explanation: In cis-1,2-disubstituted cyclohexanes, due to the cis relationship on adjacent carbons, one substituent must be axial and the other equatorial in both possible chair conformations.
15. b) Both methyl groups equatorial (e,e).
    • Explanation: trans-1,2-dimethylcyclohexane can exist as a,a or e,e. The e,e conformation is significantly more stable because it avoids the severe 1,3-diaxial interactions present in the a,a conformation and has minimized torsional strain.
16. a) The cis isomer (diequatorial).
    • Explanation: For 1,3-disubstituted cyclohexanes, the cis isomer can achieve a diequatorial arrangement (e.g., cis-1,3-dimethylcyclohexane), which is more stable than the axial-equatorial arrangement of the trans isomer.
17. c) To minimize 1,3-diaxial interactions.
    • Explanation: The primary reason for the preference of an equatorial position for a substituent in cyclohexane is to avoid the steric repulsion from the axial hydrogens (or other groups) at the 1,3-diaxial positions.
18. c) They are diastereomers.
    • Explanation: cis-1,4-dimethylcyclohexane and trans-1,4-dimethylcyclohexane are stereoisomers that are not mirror images of each other, thus they are diastereomers.
19. c) Is non-superimposable on its mirror image.
    • Explanation: The ultimate test for chirality is non-superimposability on its mirror image. While chiral centers are usually present, a molecule with chiral centers can be achiral (meso) if it has internal symmetry.
20. b) It can exist in a chair conformation where both methyl groups are equatorial.
    • Explanation: cis-1,3-dimethylcyclohexane can adopt a chair conformation where both methyl groups are in the more stable equatorial positions. This isomer is also a meso compound (achiral).
21. b) Trans relationship.
    • Explanation: When one substituent is shown with a wedge (coming out) and another with a dash (going in) on a ring, it indicates they are on opposite sides of the ring, representing a trans relationship.
22. d) cis-1,3-dimethylcyclopentane.
    • Explanation: While cis-1,2-dimethylcyclopentane is chiral (its puckered forms break symmetry), cis-1,3-dimethylcyclopentane can achieve a conformation that possesses a plane of symmetry, making it achiral (meso). The trans isomers are chiral.
23. c) 3.
    • Explanation: For 1,2-dichlorocyclopropane:
      • cis-1,2-dichlorocyclopropane is a meso compound (achiral).
      • trans-1,2-dichlorocyclopropane exists as a pair of enantiomers (two chiral molecules).
      • Total = 1 (cis-meso) + 2 (trans-enantiomers) = 3 distinct stereoisomers.
24. b) Plane of symmetry (σ).
    • Explanation: The presence of a plane of symmetry, a center of inversion, or an alternating axis of symmetry (Sn​) means a molecule is achiral, even if it has chiral centers. A C2​ rotational axis does not necessarily imply achirality.
25. c) Angled upwards and outwards.
    • Explanation: Equatorial bonds are drawn slightly angled away from the axial bonds and roughly in the plane of the ring, pointing outwards. For an “up” substituent, it angles upwards and outwards.
26. d) They are different, but equivalent in energy.
    • Explanation: For cis-1,2-dimethylcyclohexane, a ring flip interconverts the conformation with methyl groups at (1a, 2e) to one at (1e, 2a). Since the two methyl groups are identical, these two conformations are energetically equivalent. They are also mirror images of each other.
27. b) Tert-butyl equatorial, methyl equatorial.
    • Explanation: The tert-butyl group is very bulky and has a strong preference for the equatorial position due to large 1,3-diaxial interactions. For trans-1,4-disubstituted cyclohexanes, the most stable conformation is diequatorial. Therefore, placing both groups equatorially is highly favored.
28. c) Chiral.
    • Explanation: A molecule with only one chiral center will always be chiral and optically active, as it cannot possess an internal plane of symmetry or center of inversion through that single chiral center.
29. c) Decalin.
    • Explanation: Decalin, formed by the fusion of two cyclohexane rings, exhibits cis and trans isomerism at the bridgehead carbons where the rings are joined.
30. c) Trans-decalin allows both fused rings to adopt strain-minimized chair-like conformations with fewer steric interactions.
    • Explanation: Trans-decalin is more rigid and has its ring fusions in an equatorial-like orientation, leading to a more stable structure with less steric strain compared to cis-decalin’s more strained fusion.
31. d) Both b and c, with ‘c’ being more stable.
    • Explanation: For trans-1,2-disubstituted cyclohexanes, the substituents can be both axial (a,a) or both equatorial (e,e). The diequatorial (e,e) conformation is significantly more stable due to the absence of 1,3-diaxial interactions.
32. a) Cis.
    • Explanation: In cis-1,3-cyclohexanediol, a plane of symmetry can be found (passing through C2 and C5 and bisecting C1-C6 and C3-C4 bonds) when the molecule is in its diequatorial conformation. This makes it a meso compound. The trans isomer is chiral.
33. c) Achiral.
    • Explanation: Any molecule possessing a center of inversion (like a plane of symmetry) will be superimposable on its mirror image and therefore achiral.
34. c) Wedge and dash notation.
    • Explanation: Wedge and dash notation is specifically used to indicate the 3D orientation of substituents relative to the plane of the ring in cyclic structures.
35. b) Enantiomer.
    • Explanation: Enantiomers are stereoisomers that are non-superimposable mirror images of each other.
36. c) More stable than the cis isomer because it can be diequatorial.
    • Explanation: For 1,4-disubstituted cyclohexanes, the trans isomer can exist in a highly favored diequatorial conformation, which is more stable than the axial-equatorial conformation of the cis isomer.
37. d) trans-1,2-dichlorocyclobutane.
    • Explanation: trans-1,2-dichlorocyclobutane has two chiral centers and, due to its puckered nature, lacks an internal plane of symmetry, making it chiral. cis-1,2-dichlorocyclobutane is meso. cis-1,3-dichlorocyclobutane is achiral (plane of symmetry), and trans-1,3-dichlorocyclobutane is also achiral (center of inversion).
38. c) 1,3-diaxial interaction.
    • Explanation: This specific type of steric strain, involving an axial substituent and hydrogens (or other groups) three carbons away, is known as a 1,3-diaxial interaction.
39. c) Because a molecule might possess a plane of symmetry only in a particular conformation, rendering it meso.
    • Explanation: For some cyclic compounds (like 1,3-disubstituted cyclohexanes or certain cyclopentanes), a molecule with chiral centers might be able to adopt a specific conformation (often the most stable one) that possesses an internal plane of symmetry, thereby making the overall molecule achiral (meso). Therefore, one must consider the conformations to assess overall chirality.
40. c) One stereoisomer is formed preferentially over others.
    • Explanation: Stereoselective reactions do not necessarily form only one stereoisomer, nor do they always require chiral reactants. They simply show a preference for one stereoisomer over others when multiple are possible.