Cycloaddition enamine-promoted

Diels-Alder Reactions The organocatalytic Diels-Alder reaction of a,P-unsaturated carbonyl compounds can be performed either via iminium (see Section 11.3) or enamine catalysis. The first highly selective enamine-promoted cycloaddition reaction was reported by Jprgensen and coworkers, who developed an amine-catalyzed inverse-electron-demand hetero-Diels-Alder (HDA) reaction (Scheme ll.lOa). ... 

The reaction of vinyl ethers and enamines with nitroalkenes is highly regiose-lective, with only the head-to-head adduct observed. The endo approach of the dienophile is preferred in the thermal cycloaddition, however, the mode of approach can be controlled by the choice of the Lewis acid promoter (214). Facial discrimination has been obtained by the use of chiral groups on the both the nitroalkene (215,216) and the enamine (217) or vinyl ether (218), as well as with chiral Lewis acids (46,66,94,219,220). 

Asymmetric induction in the [2 + 2] cycloaddition of enamines, e.g. 42, with methyl ( )-4-oxo-4-(2-oxo-l,3-oxazolidin-3-yl)-2-butenoate (41) has been reported (equation 7)35. The reaction is promoted by a chiral titanium reagent generated in situ from dichlorodiisopropoxytitanium and a tartrate-derived chiral 1,4-diol (43). In the presence of excess amounts of the titanium reagent, 77% ee of cycloadduct 44 was achieved together with 45. The reaction also works with only a catalytic amount of the chiral reagent. 

Azetidines (215) have been synthesized by high-pressure-promoted [2 + 2] cycloadditions between imines such as 213 and / ,/i-disubstituted enamines such as 50116 in a weak polar solvent so that the dipolar intermediate 214 is neither stabilized nor intercepted (equation 46). The azetidines formed were unstable at a normal pressure and slowly decomposed into starting materials on standing. 

Even though the use of (S)-proline (1) for the synthesis of the Wieland-Miescher ketone, a transformation now known as the Hajos-Parrish-Eder-Sauer-Wiechert reaetion, was reported in the early 1970s, aminocatalysis - namely the catalysis promoted by the use of chiral second-aiy amines - was rediscovered only thirty years later. The renaissance of aminocatalysis was prompted by two independent reports by List et al. on the asymmetric intermolecular aldol addition catalysed by (S)-proline (1) and by MacMillan et al. on the asymmetric Diels-Alder cycloaddition catalj ed by a phenylalanine-derived imidazolidinone 2. These two reactions represented the archetypical examples of asymmetric carbonyl compound activation, via enamine (Figure ll.lA) and iminium-ion (Figure 11.IB), respectively. 

This type of catalyst was also employed by Christmann et al. to promote the asymmetric intramolecular Diels Alder reaction of tethered a,p-unsaturated dialdehydes in the presence of benzoic acid as a co-catalyst through vinylogous enamine activation. The corresponding cycloadducts were obtained in good yields and excellent enantioselectivities of up to 98% ee, as shown in Scheme 6.6. When one of the aldehyde functions was replaced by an a,p-unsaturated ketone as the acceptor, no formal [4 -I- 2] cycloaddition was observed instead, a direct enantioselective vinylogous Michael addition occurred. 

Quinolines and Related Compounds.— The Erythrina alkaloids have an interesting molecular architecture, and new routes to the skeleton and to the alkaloids themselves have been described recently. One approach requires the synthesis of the dibenzazonine system, which is now readily available by nickel-promoted coupling of a bis(iodophenyl)ethylamine (Scheme 90). An attempt to utilize an intramolecular [4 + 2] cycloaddition of enamines and enamides for the construction of the Erythrina carbon skeleton failed, but nevertheless provided an interesting synthesis of bridged bicyclotetrahydroisoquinolines (Scheme 91). ... 

In 2009, Bella et al. reported a formal [4 + 2] cycloaddition of substituted atylacetaldehydes and 2-cyclohexen-l-one which was promoted by a chiral thiazolidine catalyst and chiral quinine via enamine formation and spontaneous intramolecular aldol reaction (Scheme 2.4). The stereoselection depended upon the secondary amine catalyst, whereas the secondary catalyst was involved in the enhancement of the nucleophilicity of the derived enamine, probably through deprotonation of the carboxylic group. There... 

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