Enamine geometry

The enamine geometry 32 is cmcial for the stereocontrol in organocatalytic aldehyde-aldehyde couplings amines of type 31 are convenient catalysts for enantioselective enamine-aldol reactions. Examples are shown in Scheme 24 [126,131,132,133,134,135]. 

Similarly, aza-annulation with an acyclic substrate resulted in a high degree of stereocontrol. These results suggested that intramolecular hydrogen bonding of the intermediate enamine controlled the enamine geometry and served to restrict rotation of the chiral auxiliary (eq. 103).116 In this case, 507 was sensitive to hydrolysis, and isolation was performed after hydrolysis to 508. 

The catalyst structure is varied by modifying substituents at the C-2 and C-5 positions. These modifications may allow better control of the iminium, or enamine geometry, and may offer better facial selectivity in a given reaction. 

A high degree of syn selectivity can be obtained from the addition of enamines to nitroalkenes. In this case, the syn selectivity is largely independent of the geometry of the acceptor, as well as the donor, double bond. Next in terms of selectivity, are the addition of enolates. However, whether one obtains syn or anti selectivity is dependent on both the geometry of the acceptor and the enolate double bond, whereas anti selectivity of a modest and unreliable level is obtained by reaction of enol silyl ethers with nitroalkenes under Lewis acid catalysis. 

Further studies employing cnamincs of acyclic ketones have shown that the stereochemical outcome of these reactions is also independent of the geometry of the enamine component. The yyn-diastereomeric product is favored in all cases [(synjanti) >90 < 10%]n l2. 

The reaction of the enamines of cyclohexanones with a,ft-unsaluraled sulfones gives mixtures resulting from attack of the enamine at the a- and /(-carbons of the oc,/ -unsaturated sulfone. The ratio of x- and /1-adducts is dependent upon the reaction solvent, the geometry and structure of the sulfone1 4. The diastereoselectivity of these reactions is also poor. The reaction of lithium enolates of cyclic ketones with ( )-[2-(methylsulfonyl)ethenyl]benzene, however, gives bicyclic alcohols, as single diastereomers, that result from initial -attack on the oc,/ -unsaturated sulfone5. 

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. 

Decarboxylation leading to a delocalized anion (which could be an anion, an enol, or an enamine) could be treated by a model with three dimensions bond change, geometry change at carboxylate, and geometry change at the enolate carbon. Some neutral carboxylic acids might react by... 

Stereospecificity, stereoselectivity and regioselectivity combined in Diels-Alder reactions give unprecedented control and you should now see why it is so important. The analgesic tilidine 47, effective in cases of severe pain, is an obvious Diels-Alder product.8 The regioselectivity is correctly ortho and the endo transition state 51 shows that the trans -enamine 49 is needed. This is the geometry we get when the enamine is made in the normal way from the enal 50 and Me2NH. 

Use of the same substrate, with Rh(I)-(R)-BINAP yields enamine (S)-6. The exclusive formation of the ( ) enamine in all reactions irrespective of the doublebond geometry of the substrate is remarkable. Every product in the scheme can be obtained with an enantioselectivity of more than 96 % ee. 

The stereochemical outcome of the enamine can be controlled by the configuration of the olefin geometry of the allylamine and the configuration of the chiral ligand (Scheme 12.7).3642... 

The partial steps of the conjugate addition in aminocatalytic reactions are in dynamic equilibrium, and thus products are formed under thermodynamic control. This fact is translated also in the geometry of the enamine intermediates, leading to the product, which can be either E or Z (Fig. 2.9). The geometry of the enamine depends on the catalyst structure and also on the substrate. Whilst proline-catalyzed reactions form preferentially, with a-alkyl substituted ketones, the. E-isomer, enamines derived from pipecolic acid afford an approximate 1 1 mixture of the E and Z isomers [6], In turn, small- and medium-sized cyclic ketones afford the E isomer. 

In fact, the enol ether of this compound is easily made from diethyl malonate and ethyl orthoformate [HC(OEt)3]. The aromatic amine reacts with this compound by an addition-elimination sequence giving an enamine that cyclizes on heating. This time there is no worry about the geometry of the enamine. 

Vinylamine (R1 = R2 = R3 = H) is the simplest primary enamine. It was prepared by gas-phase pyrolysis of ethylamine and characterized by its microwave spectrum which led to a crude determination of its molecular geometry56. The interesting question refers to the extent of planarity or tetrahedral geometry of the amino group and this is discussed in the section on calculations of molecular structures. 

The experimental geometry of the enamine group varies from one molecule to another and there are even marked differences between the same molecule in different crystalline environments (e.g. 78 A and B and 81 A and B). 

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