Mechanistic and Stereochemical Aspects

The mechanism of the Diels-Alder reaction is now fairly well understood. The accumulated evidence favors a picture in which reorganization of the ir-electrons in the transition state for the reaction occurs so the two new a-bonds are formed in a simultaneous, concerted fashion little charge or free-radical character is developed See more on at any of the terminal carbon atoms (Eq. 12.2). The reaction is one of a number of 

Pericyclic Reactions pericyclic reactions that are controlled by orbital symmetry. Detailed discussions 

There is a second type of stereoselectivity that is characteristic of the Diels-Alder reaction. The addition of a dienophile such as maleic anhydride to a cyclic diene like 1,3-cyclopentadiene could provide two products, the endo-adduct 2 and the exoadduct 3 (Eq. 12.5). However, only the e do-cycloadduct 2, in which the two boldfaced hydrogens are syn to the one-carbon bridge, is observed experimentally, and its preferential formation follows what is now commonly termed the Alder rule. The basis for this result is believed to be stabilization of the transition state 4 by secondary orbital interactions that occur through space between the p-orbitals on the internal carbons of the diene and the carbonyl carbon atoms of the dienophile, as shown by the dashed lines in 4. Analogous stabilization is not possible in transition state 5. Structure 4 is thus characterized as the one being stabilized by maximum orbital overlap. It should be noted that not all Diels-Alder reactions are as stereoselective as the one between l,3 yclopentadiene and maleic anhydride mixtures of endo-and cxo-products are sometimes obtained. 

---

In a series of three papers, Noguchi and co-workers have reported their continuing studies on the formation of heterocycle-fused azepine systems <96X13081, 96X13097, 96X13111>. A typical example is the conversion of the aldehyde 15 into the azepines 16 and 17 (Scheme 3). Xhe reaction also proceeds with imines when the dihydroazepine prior to bridging can be isolated. Mechanistic and stereochemical aspects of the reaction have been explored. 

A fundamental understanding of the mechanistic and stereochemical aspects of the Diels-Alder reaction was unfolded during the 1970s. Several theoretical approaches are available nowadays from which Fukui s Frontier Molecular Orbital theory (FMO theory) is most frequently used because of its simplicity49- 53. 

Fig. 10.27. Mechanistic and stereochemical aspects of the hydration of trans-(R,K)-anethole epoxide in the absence (Reactions a and b) and presence of epoxide hydrolase (Reaction c) [178][179]. The ratio of Reaction a to bis ca. 4 1 in acid- and base-catalyzed hydration to yield the threo- and erythro-diols, respectively. The enzymatic Reaction c also yields preferentially the erythro-diol.

Some Mechanistic and Stereochemical Aspects of Sepulchrates and Related Encapsulating Ligands... 

The hetero-DielsAlder reaction of A-sulfinyl 141 (X = 0 or NR) or thionitrosoarene 144 dienophiles with dienes 142 is the main method for the formation of 3,6-dihydro-2//-l,2-thiazine 1-oxides 143 or 3,6-dihydro-2//-1,2-thiazines 145 (Scheme 73) . The mechanistic and stereochemical aspects of this reaction are covered in detail in GHEC-II . In general, thionitrosoarenes 144 are transient in nature, rather difficult to prepare, and thus have a limited role in the synthesis of 1,2-thiazines. On the other hand, A-sulfinyl compounds 141 and related sulfur diimines are more stable and are isolable species. The common method of preparation of the A-sulfinyl compounds involves treatment of an amine or amide with SOCl2 and base. 

The addition of nitrosyl chloride to alkenes is a well-known reaction1 3, nevertheless the mechanistic and stereochemical aspects are still not properly understood. The course of the reaction depends on the nature of the alkene and the experimental conditions. After the initial addition step, which gives a blue or sometimes green 1 1 adduct, three competitive pathways may be followed 1) dimerization of the nitroso group to give a white crystalline compound 2) oxidation of the nitroso group to a nitro group (see Section 7.2.1.8) 3) isomerization to a-chloro oximes. 

Mechanistic and stereochemical aspects of the reaction of benzothiazolyl sulfones with aldehydes were thoroughly analyzed in the JuUa works [8,9] and in the Blakemore review [98]. 

Most reactions of Grignard reagents acting as a base involves enoiates. Several papers describe mechanistic and stereochemical aspects of magnesium enoiates. Others deal with purely synthetic transformations. This section will focus specifically on magnesium enoiates. Mechanistic studies are first reviewed, followed by general synthetic applications. 

The first part of this review is dedicated to the polymerization of methyl methacrylate. This is by far the most extensively studied Grignard polymerization system. Some mechanistic and stereochemical aspects of this particular reaction are still controversial, but the results reported by independent research groups are, on the whole, mutually consistent. Other vinyl monomers have been reported to polymerize with the use of organomagnesium compounds. They are regrouped in the subsequent section. The reported results are classified and briefly commented. Studies of many systems led to contradictory results, and no attempt was made to reconcile the resulting divergent interpretations. 

Hickmott, P. W. Enamines recent advances in synthetic, spectroscopic, mechanistic, and stereochemical aspects. II. Tetrahedron 1982,... 

The addition reaction between amines and carbon disulphide has attracted the attention of several research groups because it constitutes a common route to dithiocarbamates. In their latest paper, Fitton and his co-workers, by means of cross-over experiments and the application of optically labelled bases, have further established that the reaction of benzylic, tertiary amines with carbon disulphide proceeds by an inter-molecular addition-elimination-recombination mechanism. On the other hand, Kreutzkamp and his co-workers claim that the insertion reaction of carbon disulphide with tertiary Mannich bases proceeds by an intramolecular mechanism. The synthesis of thiazolidine-2-thiones by the insertion reaction of carbon disulphide with aziridines has been the subject of two recent papers. - One of these deals mainly with the mechanistic and stereochemical aspects of this reaction, which was studied using 2-substituted and cis- and rra/z5 -2,3-disubstituted aziridines as reactants. A mechanism accounting for the stereoselectivity of the reaction has been drawn up by the authors (Scheme 7). 

Rearrangements.—Mechanistic and stereochemical aspects of the photochemical ring expansion of cyclic ketones via oxacarbenes have been discussed. Evidence for a quantum chain process in the photoreactions of benzvalene is reported, and hydrogen-abstraction reactions and subsequent rearrangements of 1,3-diene-p-benzoquinone Diels-Alder adducts have been extensively investigated. ... 

The mechanistic and stereochemical aspects of the individual steps of Scheme 9.2, which contribute to the elegance of this route, wiU now be discussed in more detail. 

P. W. Hickmott, Enamines Recent Advances in Synthetic, Spectroscopic, Mechanistic, and Stereochemical Aspects - 1, Tetrahedron, 1982, 38, 1975. 

See Section 2.6 for discussion of the mechanistic and stereochemical aspects of this elimination.) Because C-8 is reconverted to sp hybridization, the stereochemistry up to this point is not crucial. The final stereochemistry at C-8 is established by protonation of the silyl enol ether. Evidently the C-10 methyl group again is the controlling factor. After the aldehyde group is in place it is reduced... 

Hickmott PW (1982a) Enamines recent advanees in s3Tithetie, spectroscopic, mechanistic, and stereochemical aspects-I. Enamines reeent advances in synthetic, spectroscopic, mechanistic, and stereochemical aspects-1. Tetrahedron 38(14) 1975-2050. doi 10.1016/0040-4020(82) 85149-1... 

---