Stereoselectivity bond formation

Both type A and B transformations are kinetically controlled and, therefore, the stereochemical result is based on an energetic comparison of transition states. By contrast, there is a large group of reactions where stereoselective bond formation occurs under thermodynamic control, and the stereoselectivity stems from the energy difference of the stereoisomeric products. Section 2.3.6. describes some pertinent examples. 

A. De Mesmaeker, P. Hoffmann, and B. Ernst, Stereoselective bond formation in carbohydrates by radical cyclization reactions. Tetrahedron Lett. 29 6383 (1988). 

If one subscribes to the oxocarbenium-centric theory of glycosidic bond formation [20, 21], it is apparent from Scheme 5.2 that the grounds for stereoselective bond formation are slim. This is because neither of the two possible interconverting halfchair conformers of the oxocarbenium ion (4H5 and 5H4) appear to exhibit any overwhelming steric preference for one face of the system over the other [22],... 

Furthermore, this regio- and stereoselective bond formation between unsaturated carbon atoms was applied to the synthesis of functionalized dienes under extremely mild conditions. Thus, even vinylic boronic esters containing an allylic acetal moiety and alkenylboronate having a chiral protected allylic alcohol were successfully accomplished with vinylic iodides under aqueous conditions in 60-90% yield [30]. In addition, an exceptionally simple and efficient synthesis of a prostaglandin (PGEj) precursor was reported by Johnson, applying a DMF/THF/ water solvent mixture with a bis(diphenylphosphino)ferrocene palladium catalyst [31]. It is curious that the presence of water is an absolute necessity in order to succeed in this approach (Scheme 3). 

The thermal reaction of dialkyl-ketens and -allenes to yield alkylidenecyclo-butanones has been the subject of detailed studies by Bertrand et The reaction is regiospecific and stereoselective. Bond formation takes place between the central bond of the keten and the allene. Use of chiral allenes gives optically active alkylidene-cyclobutanones. With an allene of the R configuration (109), the newly formed chiral centre in the products, (110) and (111), also has the R configuration, irrespective of whether the product has an exocyclic olefinic residue of the E or Z configuration. 

The ate complexes 80 can be similarly employed in the coupling of organic substituents on aluminum. The addition of 1-alkynyllithium to the 1-alkenylalu-minum 79, followed by treatment with VO(OEt)Cl2, leads to the trans-enyne 81 via chemoselective and stereoselective bond formation between sp and sp carbons (Scheme 2.67) [136]. 

An ammonium betaine of type (R)-16 could be considered as an intramolecular version of ammonium phenoxide. The potential of chiral ammonium betaine (R)-16 as Brpnsted base catalyst has been demonstrated in asymmetric Mamiich reactions (Scheme 14.9) [6b, 32]. The basic phenoxide anion is responsible for abstraction of the active methine proton of a nucleophile 18 and thus gives the corresponding chiral ammonium enolate. Subsequent stereoselective bond formation with imine 17 afforded ammonium amide that can be rapidly protonated by the in situ formed phenolic hydrogen to regenerate the ammonium betaine (R)-16. 

Scheme 17.13 Selected examples of proline-catalyzed reactions where the enantiomeric excess has been predicted by using DFT computations with enamines in the stereoselective bond formation.

Newly designed chiral tetraaminophosphonium salt 184 possessing an organic anion cooperatively catalyzes asymmetric Mannich-type reaction of azlactones (182) with N-sulfonyl imines (183) (Scheme 28.20). The basic carboxylate anion deprotonates the active methine proton of the azlactone (182) to form the corresponding chiral phosphonium enolate with a defined hydrogen bonding network (ion pair), and then highly stereoselective bond formation proceeds [92]. 

---