Asymmetric electrocyclic reactions

A review of the use of electrocyclic reactions in synthesis has been presented" and of asymmetric electrocyclic reactions that result in diastereo- or enantio-selectivity selection as a consequence of the influence of a chiral component, be it substrate or catalyst, on the electrocyclic bond-forming process." Computational studies of 0 electrocyclic ring-opening reactions of 2-pyrone and 6-fluoro-2-pyrone are pseudoper-icyclic 6-fluoro-2-pyranol are a borderline case and 2-pyranol, pyran, and 6-fluoro pyran reactions are pericyclic in character." ... 

The Nazarov Cyclization is a rare example of a Lewis acid-catalyzed 4-7t conrotatory electrocyclic reaction. Asymmetric... 

Asymmetric Br0nsted Acid Catalyzed Carbonyl Activation The First Organocatalytic Electrocyclic Reaction... 

A4) of a compound with three tt bonds is asymmetric (Figure 29.3). Therefore, under Lm 3u LergJngring°doVu photochemical conditions, (2 ,4Z,6Z)-octatriene undergoes conrotatory ring closure, controls the stereochemical outcome so both methyl groups are pushed down (or up) and the cis product is formed. of an electrocyclic reaction. 

We have just seen why the configuration of the product formed under photochemical conditions is the opposite of the configuration of the product formed under thermal conditions The ground-state HOMO is symmetric—so disrotatory ring closure occurs, whereas the excited-state HOMO is asymmetric—so conrotatory ring closure occurs. Thus, the stereochemical outcome of an electrocyclic reaction depends on the symmetry of the HOMO of the compound undergoing ring closure. 

Electrocyclization reactions of unsaturated esters and enones in solution have led to very low asymmetric inductions, and the origin of the selectivity observed is not completely understood [56-59]. When inclusion complexes (1 1) of 19, 22, and 247 with chiral hosts 241b or c, were irradiated in the solid state, almost complete enantioselectivity was observed (Scheme 39). 

Asymmetric electrocyclizations have been rarely reported in the literature, either for chiral auxiliary approaches or for asymmetric catalytic processes [73]. The main reason for this is most likely due to the generally high activation energies for these reactions, which complicates the engineering process of finding substrates and catalysts that enabled the system to react at reasonable temperatures required to obtain good stereoselectivity. 

Reaction of enaminonitfiles with a, -unsaturated aldehydes catalysed by BF3 OEt2 gives 1-azatrienes which undergo 1,6-electrocyclizations to 1,2-dihydropyridines. A Br0nsted-acid-catalysed asymmetric 6 r-electrocyclization reaction has been reported for the synthesis of enantiomerically enriched 1,4-dihydropyridazines (Scheme 39). ... 

Next, another work on a Br0nsted acid-catalyzed intramolecular electrocyclization reaction was reported by list [36]. They demonstrated that chiral Bronsted acid 104 could efficiently promote the cycloisomerization of a,P-unsaturated hydrazones 105 to give pyrazoUnes 106 in high yields and with good enantioselectivity (Scheme 36.28). This is also the first example of an organocatalytic asymmetric 671 electrocyclization reaction. 

Rueping M, leawsuwan W, Antonchick AP, Nachtsheim BJ. Chiral Brpnsted acids in the catalytic asymmetric Nazarov cyclization-the first enantioselective organocatalytic electrocyclic reaction. Angew. Chem. Int. Ed. 2007 46 2097-2100. 

When the reaction is conducted in the presence of added fumarate, the yield of pyrrolidine (130) increases at the expense of the aziridine. Jacobsen suggests that the aziridines and pyrrolidines arise from a common intermediate, azo-methine ylide (132), Scheme 6, which may also be partly responsible for the poor levels of asymmetric induction in this reaction. Electrocyclic ring closure of the azo-methine while still within the coordination sphere of the metal (131) may provide aziridine with some induction, while decomplexation (132) will lead to the formation of racemic aziridine and pyrrolidine. 

Arenes suffer dearomatization via cyclopropanation upon reaction with a-diazocarbonyl compounds (Btlchner reaction) [76]. Initially formed norcaradiene products are usually present in equilibrium with cycloheptatrienes formed via electrocyclic cyclopropane ring opening. The reaction is dramatically promoted by transition metal catalysts (usually Cu(I) or Rh(II) complexes) that give metal-stabilized carbenoids upon reaction with diazo compounds. Inter- and intramolecular manifolds are known, and asymmetric variants employing substrate control and chiral transition metal catalysts have been developed [77]. Effective chiral catalysts for intramolecular Buchner reactions include Rh Cmandelate), rhodium carboxamidates, and Cu(I)-bis(oxazolines). While enantioselectivities as high as 95% have been reported, more modest levels of asymmetric induction are typically observed. 

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