Question

Reaction of the following \(S\) tosylate with cyanide ion yields a nitrile product that also has \(S\) stereochemistry. Explain. ( \(S\) stereochemistry)

Short answer

The product retains (S) stereochemistry by retention despite the possible inversion mechanism, likely due to specific reaction dynamics deviating from usual inversion expectations.

Step-by-step solution

Identify the Reactants

The problem involves a tosylate substrate with an (S) stereochemistry and a cyanide ion (CN-) as the nucleophile. The reaction appears to be a nucleophilic substitution.

Consider Nucleophilic Substitution Type

There are two primary types of nucleophilic substitution reactions: SN1 and SN2. SN1 reactions involve carbocation intermediates and often result in a racemic mixture due to planar intermediate geometry, whereas SN2 reactions occur via a single step, leading to inversion of configuration at the stereogenic center.

Analyze Reaction Conditions for SN2

Given that the final product retains the (S) stereochemistry, the reaction suggests only one possible mechanism. Since SN2 involves inversion, in this case, the tosylate must leave from the opposite face it arrived, leading to an enantiomeric inversion during SN2 though the reaction setup conditions are battling to propose that SN2.

Determine Configuration Result

Assuming the tosylate reposition occurs using the SN2 route but on the opposite side for binding from the beginning, likely due to rear attack lack to another mechanism to pop into the possible dominion, can deduce the resultant changes compatible.

Conclude with Reaction Mechanism

Ordinarily, for a reaction described, product invert. However, product maintained (S) stereochemistry despite SN2 potential inverse suggestion meant realization of the substrate consequence or concise abstraction hindering the definite SN1 approach considering potential sterical or mechanistical misalignment converse overall.

Key concepts

SN1 mechanism

The SN1 mechanism is a type of nucleophilic substitution reaction characterized by a two-step process. This reaction involves the formation of a carbocation intermediate. Here's how it usually unfolds:

• First, the leaving group departs, generating a positively charged carbocation.
• Next, the nucleophile attacks this planar carbocation, leading to the formation of the product.

Due to the planar nature of the carbocation, the nucleophile can attack from either side, often resulting in a racemic mixture of products if the original substrate was chiral. This mechanism is generally favored in reactions where the carbocation is stable, such as tertiary carbocations. Factors like the solvent playing a role in stabilizing or destabilizing this carbocation can also steer the reaction toward an SN1 pathway rather than SN2. However, the stereochemical outcome in an SN1 reaction can vary depending on the structure of the substrate and the conditions.

SN2 mechanism

The SN2 mechanism is another pathway of nucleophilic substitution but occurs in a single concerted step. This mechanism is characterized by:

• The simultaneous attack of the nucleophile as the leaving group departs.
• A direct back-side attack on the electrophilic carbon, leading to an inversion of configuration.

Because of this inversion, an SN2 reaction often transforms an (S) stereoisomer into an (R) stereoisomer, or vice versa.
This process is called the Walden inversion. For SN2 reactions, substrates that are unhindered, like primary or secondary carbons, tend to react more readily, as steric hindrance can impede the back-side attack. Solvents that do not solvate the nucleophile too heavily, for instance, polar aprotic solvents, are particularly favorable for SN2 reactions. Due to these characteristics, if a reaction retains the (S) stereochemistry as per the recent example, it implies potential complications with the SN2 mechanism.

Stereochemistry

Stereochemistry involves the spatial arrangement of atoms in molecules and how these arrangements affect the physical and chemical properties. Understanding stereochemistry is crucial for recognizing how reactions influence molecule geometry:

• Chirality is a core concept, referring to molecules that are non-superposable on their mirror images.
• Stereoisomers, such as enantiomers and diastereomers, are important in this context.

For reactions like SN1 and SN2, the stereochemical outcome is integral to determining the type of mechanism. The retention or inversion of configuration, as described in this example with (S) stereochemistry, is particularly telling of the mechanistic pathway. This reaction maintains its (S) configuration, suggesting factors beyond simple inversion mechanics, perhaps involving steric or electronic influences that avert the expected outcome.

Tosylate

Tosylates are excellent leaving groups in substitution reactions. They derive from toluenesulfonic acid and are often used to convert alcohols into more reactive counterparts.

• The tosylate group, abbreviated as TsO, enhances the departure of the leaving group.
• Its excellent leaving ability is due to the resonance stabilization provided by the sulfonyl group.

In nucleophilic substitution reactions, whether SN1 or SN2, the tosylate can depart smoothly, making it a prevalent choice in synthetic organic chemistry. The exercise mentioned an (S) tosylate, suggesting that the structure was set for a nucleophilic attack. Despite an expectation of inversion in SN2 reactions, alternative complexities, including spatial arrangement or steric conditions involving tosylate positioning, can affect the path and outcome.

Cyanide ion

The cyanide ion (CN-) is a potent nucleophile frequently used in organic synthesis. Its strengths in nucleophilic substitution are due to:

• A strong nucleophilic character enabling it to swiftly attack electrophilic carbon centers.
• The ability to form strong bonds through the carbon atom of the CN group.

Cyanide ions are small and linear, making them ideal for the back-side attack required in SN2 reactions. This characteristic usually ensures effective interaction with the substrate.
However, the example reaction shows retention of (S) stereochemistry, leading to potential conclusions that cyanide's attack might not have proceeded as per typical SN2 inversion expectations. Consequently, assessing reaction conditions and substrate sterics may elucidate why the anticipated inversion of configuration did not occur in this unique case.