Question

How many stereoisomers are possible for (Q)? $$ \bigcap_{\mathrm{O}} / \underset{\mathrm{HCN}}{\stackrel{\mathrm{NaCN}}{\longrightarrow}}(\mathrm{P}) \frac{(\mathrm{i}) \mathrm{LiAlH}_{4}}{(\mathrm{ii}) \mathrm{H}_{2} \mathrm{O}}(\mathrm{Q}) $$ (A) 2 (B) 4 (C) 1 (D) 3

Short answer

The number of possible stereoisomers for compound (Q) depends on the stereochemical configurations of the three stereocenters. However, only one stereocenter undergoes a change in stereochemistry during the reaction. Since there are two possible configurations for this stereocenter, there are only two possible stereoisomers for compound (Q). Therefore, the correct answer is (A) 2.

Step-by-step solution

Identify the stereochemistry of the starting material (O) and intermediate compound (P)

The starting material (O) is an epoxide, which has two stereocenters at the C-O-C linkage. However, the problem does not provide information about the stereochemistry of these centers in (O). The intermediate compound (P) results from a nucleophilic addition of cyanide to the epoxide, creating a new stereocenter. As HCN can attack from both faces of the epoxide and neither of the existing stereochemical centers are mentioned in the exercise, intermediate (P) has three stereocenters in total, each with an unspecified configuration. While we know that the reaction created a new stereocenter, we cannot predict its stereochemical configuration without more information.

Track stereochemical changes during reaction steps involving reagents (LiAlH4 and H2O)

Once we understand the stereochemistry of the starting material (O) and intermediate (P), we need to determine how the reaction conditions and reagents influence this stereochemistry. Treatment of compound (P) with LiAlH4 (step i) reduces the nitrile group to an amine while maintaining all three stereocenters from compound (P). Consequently, the differing stereochemical configurations of the initial compound (O) will lead to different configurations at the corresponding stereocenter in the amine product of reaction (i). The treatment of the product from step (i) with H2O (step ii) is essentially a protonation step that does not change the stereochemistry. Therefore, the stereochemical configurations of the product (Q) are retained from the original stereocenters in compound (P) (which in turn are determined by the original stereocenters in compound (O)).

Determine the number of possible stereoisomers for compound (Q)

Since the product (Q) maintains its stereochemical configurations throughout the reaction sequence, we can determine the number of possible stereoisomers based on the three stereocenters present in compound (P) (and ultimately compound (O)). With three chiral centers, there are 2^3 = 8 possible stereoisomers. Since the problem does not provide any limitations or restrictions on the stereochemistry of these stereocenters, all 8 possible combinations are potentially valid. However, a closer inspection reveals that only one stereocenter changes its stereochemistry during the course of the reaction (the one created by the nucleophilic attack of HCN). Indeed, the stereochemistry of the other two stereocenters is kept throughout the reaction sequence and is not influenced. Hence, we have only two possible configurations at the new stereocenter, which means there are only two possible stereoisomers for compound (Q). The correct answer is (A) 2.

Key concepts

Stereochemistry

Stereochemistry explores the spatial arrangement of atoms within molecules, particularly how these arrangements influence the physical and chemical properties of substances. One key aspect is how different spatial configurations, or stereoisomers, might have distinct characteristics, even though they have the same molecular formula.

To illustrate, imagine your hands; they are mirror images of each other, similar yet non-superimposable – this is what we call chirality in stereochemistry. When a molecule has different spatial configurations, each unique arrangement is called an isomer. The significance of stereochemistry is paramount in fields like pharmaceuticals, where one isomer might be therapeutic while another could be inert or even harmful.

Understanding the stereochemical principles helps students predict the outcomes of chemical reactions, comprehend the behavior of molecules, and explain the vast diversity of organic structures found in nature. Following these principles, we track how stereochemistry is key to identifying the number of potential stereoisomers for a compound during synthesis.

Stereocenters

A stereocenter is a point in a molecule where the swapping of two groups leads to a different stereoisomer. The most common type of stereocenter is the chiral center, usually a tetrahedral carbon atom bonded to four different groups.

Every stereocenter in a molecule contributes to its chiral nature, and with each additional chiral center, the number of potential stereoisomers increases exponentially. This relationship is because each stereocenter can exist in one of two configurations (R or S, based on the Cahn-Ingold-Prelog priority rules), leading to a total count of isomers equal to 2^n, where n is the number of stereocenters.

For educational exercises, it's critical to show students how to identify and analyze stereocenters because it builds the foundational understanding necessary for complex stereochemical predictions. This understanding is necessary when solving problems involving the synthesis of chiral compounds where maintaining or modifying the stereochemistry at each center can lead to different outcomes.

Nucleophilic Addition

Nucleophilic addition is a foundational reaction in organic chemistry where an electron-rich nucleophile attacks an electron-deficient carbon. This process often occurs in carbonyl compounds—aldehydes and ketones—where the carbon atom of the carbonyl group is the electrophilic site.

In the context of the textbook problem, we delve into a nucleophilic addition involving an epoxide where a cyanide ion, acting as the nucleophile, opens the three-membered ring to create a new stereocenter. This reaction is critical as it can introduce chirality into a molecule. The nucleophile can attack from either side of the planar carbonyl group, or in this case, the less hindered face of the epoxide, resulting in the formation of one of two possible enantiomers at the new stereocenter.

Students can be guided to visualize these reactions through models or diagrams, reinforcing their spatial reasoning and ability to predict the outcome of such additions. This visualization enhances their grasp of stereochemistry and its real-world applications in designing drugs and understanding biological processes where the molecular handedness can be a key factor.