Tetrahedral products formation

When enzymes like alcohol dehydrogenase, are chiral, reduce carbonyl groups using coenzyme NADH, they discriminate between the two faces of the trigonal planar carbonyl substrate, such that a predominance of one of the two possible stereoisomeric forms of the tetrahedral product results, i) If the original reactant was chiral, the formation of the new stereocenter may result in preferential formation of one diastereomer of the product => a diastereoselectiv reaction. 

The authors proposed mechanism involves initial attack of an in sitn formed carbene onto the aldehyde to produce tetrahedral intermediate LXXIII (Scheme 47). Proton transfer wonld produce an acyl anion eqnivalent, bnt is inconsistent with product formation. Instead S 2 displacement to produce ring opened intermediate LXXIV is proposed, followed by proton transfer. At this point, molecular oxygen apparently becomes involved to oxidize nncleophilic alkene LXXV. The active catalyst is then regenerated and observed prodnct is formed. 

In contrast, Equations 6.8-6.10 show the rate of product formation for an acylation by the two-step route in Figure 6.3, assuming that the tetrahedral intermediate is formed reversibly. Interestingly, it does not matter whether in the rate-determining step the tetrahedral intermediate is formed (k < kdJ or reacts further (then fcetro > kdJ. 

If it is assumed that the adsorbed carbonium ion has a tetrahedral configuration, it is evident that the cis-adsorbed species is sterically more favorable than the trans species. Thus, hydride ion transfer to the adsorbed charged species from the catalyst would lead to predominant cis-product formation. In contrast to the Weidlich proposal, these mechanisms call for a 1,4-addition of hydrogen in acidic media. The concept of a hydride ion transfer from the catalyst is not unique to these mechanistic proposals. Hydride ions have been proposed to take part in the catalytic hydrogenolysis of certain substituted cyclopropanes... 

Figure 8. Proposed catalytic mechanism for carboxypeptidase A where Glu270 acts as the nucleophile a) nucleophilic attack by carboxylate oxygen of Glu270 on the carbonyl carbon of the substrate b) forming a tetrahedral intermediate c) the intermediate breaks down to give an anhydride species d) hydrolysis of the acylenzyme leads to product formation and regnerates the free enzyme...

Figure 9. Proposed catalysic mechanism for carboxypeptidase A where water acts as the nucleophile, (a) nucleophilic attack by a water molecule on the carbonyl carbon of the substrate promoted by zinc and assisted by Glu270 with concommitant transfer of i proton to Glu270 (b) a tetrahedral intermediate, stabilized by interactions with Argl27 and the zinc ion, collapses with a proton donated by Glu270 (c) a second proton transfei results in product formation (d).

Steric Factors In aldehydes, where one group is a hydrogen atom, the central carbon of the tetrahedral product formed from the aldehyde is less crowded and the product is more stable. Formation of the product, therefore, is favored at equilibrium. With ketones, the two alkyl substituents at the carbonyl carbon cause greater steric crowding in the tetrahedral product and make it less stable. Therefore, a smaller concentration of the product is present at equilibrium. 

In the addition reactions of aldehydes and ketones, a tetrahedral product forms because of attack of a nucleophile at the carbonyl carbon atom. Examples include the formation of hemiacetals with alcohols, and the synthesis of alcohols using the Grignard reagent. 

Transition-state stabilization in chymotrypsin also involves the side chains of the substrate. The side chain of the departing amine product forms stronger interactions with the enzyme upon formation of the tetrahedral intermediate. When the tetrahedral intermediate breaks down (Figure 16.24d and e), steric repulsion between the product amine group and the carbonyl group of the acyl-enzyme intermediate leads to departure of the amine product. 

Aldehydes and unhindered ketones undergo a nucleophilic addition reaction with HCN to yield cyanohydrins, RCH(OH)C=N. Studies carried out in the early 1900s by Arthur Eapworth showed that cyanohydrin formation is reversible and base-catalyzed. Reaction occurs slowly when pure HCN is used but rapidly when a small amount of base is added to generate the nucleophilic cyanide ion, CN. Alternatively, a small amount of KCN can be added to HCN to catalyze the reaction. Addition of CN- takes place by a typical nucleophilic addition pathway, yielding a tetrahedral intermediate that is protonated by HCN to give cyanohydrin product plus regenerated CN-. 

Imine formation and enamine formation appear different because one leads to a product with a C=N bond and the other leads to a product with a C=C bond. Actually, though, the reactions are quite similar. Both are typical examples of nucleophilic addition reactions in which water is eliminated from the initially formed tetrahedral intermediate and a new C=Nu bond is formed. 

Following formation of the amide intermediate, a second nucleophilic addition of hydroxide ion to the amide carbonyl group then yields a tetrahedral alkoxide ion, which expels amide ion, NHZ-, as leaving group and gives the car-boxylate ion, thereby driving the reaction toward products. Subsequent acidification in a separate step yields the carboxylic acid. We ll look at this process in more detail in Section 21.7. 

The strained bicyclic carbapenem framework of thienamycin is the host of three contiguous stereocenters and several heteroatoms (Scheme 1). Removal of the cysteamine side chain affixed to C-2 furnishes /J-keto ester 2 as a possible precursor. The intermolecular attack upon the keto function in 2 by a suitable thiol nucleophile could result in the formation of the natural product after dehydration of the initial tetrahedral adduct. In a most interesting and productive retrosynthetic maneuver, intermediate 2 could be traced in one step to a-diazo keto ester 4. It is important to recognize that diazo compounds, such as 4, are viable precursors to electron-deficient carbenes. In the synthetic direction, transition metal catalyzed decomposition of diazo keto ester 4 could conceivably furnish electron-deficient carbene 3 the intermediacy of 3 is expected to be brief, for it should readily insert into the proximal N-H bond to... 

The formation of dimeric products is unique for the case of boron, because analogous complexes with other elements are all monomeric [95]. This can be attributed to the small covalent radius of the boron atom and its tetrahedral geometry in four-coordinate boron complexes. Molecular modeling shows that bipyramidal-trigonal and octahedral coordination geometries are more favorable for the formation of monomeric complexes with these ligands. 

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