Enamines orthogonal

One of the most widely applied cycloaddition techniques for the preparation of thietanes is the reaction of sulfenes with enamines. The stereochemistry of these reactions has been extensively investigated by Truce and Rach. Whether the mechanism is a two-step or a concerted process, both in accordance with the stereoselective formation of the cis form in Scheme 1, is still unresolved. The special orientation of the 1,4-dipolar intermediate 64, in which the charged phenyl and dimethylamino moieties are in proximity, enforces the cis geometry of the resulting thietane dioxide. In the concerted mode of reaction, formation of the orthogonal oriented unsaturated system, 65 should also yield the cis cycloadduct. 

If N-protonation of enamines would occur, their UV spectrum should be strongly shifted hypsochromically to an absorption close to that of the corresponding alkene. This may be inferred from the agreement of the UV absorption of styrene (232) Wmax = 248 nm, max = 15,000)334 with that of w-styryltrimethylammonium bromide344 (233) (Amax = 247 nm, max = 15,350). The UV absorption of the bicyclic orthogonal... 

The introduction of a methyl group at C(2) of aminocyclohexenes causes a large downfield shift (+ 22 to +26 ppm) of the resonance of this carbon which can be explained by a large allylic 1,3-strain ( 4 ) in the tetrasubstituted coplanar enamine. Theoretical calculations - as well as the results of photoelectron spectroscopy and X-ray crystallographic studies indicate that in unhindered enamines with the nitrogen lone pair nearly orthogonal to the C=C plane, one of the substituents of the flattened... 

Systematic studies on the isomerization of W-allylamides 24 and -imides to aliphatic enamides 25 were carried out with iron, rhodium, and ruthenium complexes as catalysts, Eq. (8). Regrettably, no prochiral substrate was applied for the rhodium catalyst bearing polymer-anchored DIOP [33]. In the framework of a study on the conjugative interaction in the isomerization of 1-azabicyc-lo[3.2.2]non-2-ene 26 to orthogonal enamine 27, catalyzed by either f-BuOK or RuH(NO)(PPh3)3, the enamine formation was calculated to be favored by 4 kcal mob, Eq. (9) [34]. Recently, the palladium-catalyzed isomerization of the N-acyl-2,5-dihydropyrroles 28 to N-formyl-2,3-dihydropyrroles 29 was reported, Eq. (10) [35]. 

Figure 6.108 Switch from the selective fEattack in normal enamines to an a-attack in the "orthogonal" enamine in reaction with HBr.

When two bulky groups are attached at the nitrogen atom (i.e. in Z-substituted enamines), steric hindrance imposed by these groups is unavoidable and can strongly disfavor the coplanar conformation. In such systems, the nitrogen lone pair can assume a misaligned (even orthogonal) orientation, with the partial loss of the interaction or, in the extreme case of (Z)-l-(dimethylamino)-propene, with the replacement... 

This study provided one of the first demonstrations [24] that chiral secondary amines can integrate orthogonal activation modes of carbonyl compounds (enamine and iminium ion catalysis) into more elaborate reaction sequences, catalyzing more than one stereocontroUed bond-forming event As detailed in Section 42.2.2, this concept greatly permeated and boosted future developments in the field of asymmetric organocatalytic MCRs. 

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