Question

Organocuprates predominantly react to give 1,4 -addition products with \(\alpha, \beta\)-unsaturated carbonyl species, while Grignard reagents often add to the carbonyl, in a process referred to as 1 ,2-addition. To increase the yield of 1,4 -addition products CuI is added to convert an easily prepared Grignard reagent into a organocuprate reagent in situ (during the reaction). Predict the major product and stereochemistry of the following reaction, assuming the more stable chair product predominates.

Short answer

Question: Predict the major product and stereochemistry of a reaction between an organocuprate reagent and an α,β-unsaturated carbonyl species. Answer: The major product of the reaction will be the more stable chair product formed through the 1,4-addition mechanism, which takes place with retention of the stereochemistry on the α-carbon. The stereochemistry could be syn or anti-addition depending on the confirmation of the organocuprate species attacking the substrate.

Step-by-step solution

Identify the reactants

In the given reaction, we have \(\alpha, \beta\)-unsaturated carbonyl species, which contain multiple bonds along with a carbonyl group (C=O) and a Grignard reagent which is a carbon-metal bond.

Formation of organocuprate reagent in situ

To generate an organocuprate reagent in situ, CuI is added to the Grignard reagent. This leads to the formation of an organocuprate species, which has a copper atom bonded to the carbon atom.

Performing the 1,4-addition on the unsaturated carbonyl species

In the 1,4-addition reaction, the organocuprate reagent attacks the β-carbon of the unsaturated carbonyl species, and the negatively charged species adds to the α-carbon. This results in a new carbon-carbon bond formation. Simultaneously, the carbonyl group gets progressively polarized leading to the formation of a new six-membered transition state.

Predicting the major product

As the reaction proceeds through the six-membered transition state, the formation of the more stable chair product takes place, thus it will predominate in the reaction mixture. Following the reaction mechanism, the major product can be predicted.

Predicting the stereochemistry of the major product

Since the more stable chair product predominates, the reaction proceeds with retention of stereochemistry on the α-carbon. This leads to either syn or anti-addition to the unsaturated carbonyl species depending on the confirmation of the organocuprate species attacking the substrate. Considering the entire reaction mechanism, the stereochemistry of the major product can be predicted.

Key concepts

1,4-addition

In organometallic reactions, understanding the concept of "1,4-addition" is crucial for predicting product formation. This type of addition occurs when the nucleophile, in this case, an organocuprate reagent, attacks the β-carbon of an α,β-unsaturated carbonyl compound. A distinct feature of 1,4-addition is that it leads to the formation of new carbon-carbon bonds at the β-position, while the carbonyl remains intact.
The mechanism involves temporary polarization of the carbonyl group, leading to a more stable six-membered ring transition state. This often results in producing a more stable product compared to direct 1,2-addition at the carbonyl carbon.
Understanding the preference for 1,4-addition in organocuprate reactions is fundamental when considering how various reagents might react with α,β-unsaturated carbonyl compounds.

Grignard reagents

Grignard reagents are a cornerstone of carbon-carbon bond-forming reactions in organic chemistry. These reagents usually consist of a magnesium halide complex bonded to an organic moiety. Due to their structure, they are highly reactive and typically perform 1,2-additions to carbonyl groups.
However, when forming organocuprate reagents for 1,4-addition, CuI is added to convert the Grignard reagent in situ. This transformation adjusts the reactivity, shifting the focus from direct carbonyl addition to β-carbon attack on α,β-unsaturated carbonyl species, making the reaction versatile for synthesizing complex molecules.
The choice between using Grignard reagents directly and converting them to organocuprate forms is pivotal depending on the desired outcome of the organic synthesis process.

Stereochemistry

Stereochemistry involves the study of spatial arrangements in molecules, which is vital when predicting the outcomes of organic reactions. In the context of α,β-unsaturated carbonyl compounds undergoing organocuprate reactions, stereochemistry dictates the three-dimensional shape of the resulting product.
The reaction leads to a favored chair conformation due to its stability in forming six-membered rings. This stability ensures retention of stereochemical configuration, favoring specific diastereomers.

• The syn-addition or anti-addition depends mainly on the orientation of the organocuprate during the attack.
• It's crucial to analyze potential reaction pathways to predict the stereochemical outcome accurately.

Understanding stereochemistry is key to designing synthetic pathways that yield the desired chiral centers for complex organic molecules.

α,β-unsaturated carbonyls

α,β-Unsaturated carbonyls are compounds featuring a carbonyl group (C=O) conjugated with a carbon-carbon double bond. This structure facilitates unique reactivity patterns, distinguishing them from non-conjugated carbonyl compounds.
Their susceptibility to 1,4-addition is due to the electron-deficient β-carbon, making it an attractive position for nucleophilic attack. This property is exploited by organocuprate reagents formed from Grignard reagents, targeting the β-position efficiently.
The distinguishing feature of these compounds is the delicate balance they maintain between π-electron stability and reactivity at specific sites, which can be finely tuned with specific reagents. Understanding these properties aids chemists in employing them as pivotal intermediates in diverse synthetic schemes.

Organometallic chemistry

Organometallic chemistry bridges the gap between organic and inorganic chemistry, focusing on compounds containing metal-carbon bonds. These compounds, like organocuprates, play a key role in facilitating unique organic transformations, enhancing reaction scope and selectivity.
Organocuprate reagents, with their metal (copper) center, stabilize the organic moiety, allowing nucleophilic attack on less reactive centers such as the β-carbon in α,β-unsaturated carbonyls.
Through organometallic chemistry, synthetic routes gain finesse, enabling the formation of complex, structurally specific organic molecules efficiently. Knowledge of metal-carbon interactions within these compounds is essential for advanced applications in organic synthesis.