Facial selectivity intramolecular cycloadditions

Chelation is also thought to play an important part in directing the facial selectivity of cycloadditions with the camphor sultam auxiliary. A variety of dienes can be used and adducts are obtained with very high diastereomeiic excesses. Both inter-and intramolecular cycloaddition reactions are amenable to the use of a chiral auxiliary. An intramolecular example is illustrated in Scheme 3.93, in which the diene and dienophile are tethered and in which cycloaddition leads to predominantly one of the two diastereomeric trans-fusQd bicyclic (endo) products. The dienophile is thought to adopt the s-cis conformation, with the aluminium atom complexed to the carbonyl and one of the two sulfone oxygen atoms. 

Our initial studies focused on the transition metal-catalyzed [4+4] cycloaddition reactions of bis-dienes. These reactions are thermally forbidden, but occur photochemically in some specific, constrained systems. While the transition metal-catalyzed intermole-cular [4+4] cycloaddition of simple dienes is industrially important [7], this process generally does not work well with more complex substituted dienes and had not been explored intramolecularly. In the first studies on the intramolecular metal-catalyzed [4+4] cycloaddition, the reaction was found to proceed with high regio-, stereo-, and facial selectivity. The synthesis of (+)-asteriscanoHde (12) (Scheme 13.4a) [8] is illustrative of the utihty and step economy of this reaction. Recognition of the broader utiHty of adding dienes across rc-systems (not just across other dienes) led to further studies on the use of transition metal catalysts to facilitate otherwise difficult Diels-Alder reactions [9]. For example, the attempted thermal cycloaddition of diene-yne 15 leads only... 

This section shall consider the effects of substitution on both the nitronate as well as the dipolarophile, as they relate to both the inter- and intramolecular versions of the dipolar cycloaddition. Also included will be a discussion of facial selectivity in the reaction of a chiral dipolarophile. 

RC=CKWG) yields 2,4-di-EWG-substituted pyrroles in the presence of copper catalyst but 2,3-di-EWG-substituted pyrroles in the presence of a phosphine catalyst.74 The 3 + 2-cycloaddition of diazoalkanes to (6 )-3-p-tolylsulfinylfuran-2(5//)-one produces diastereoisomeric pyrazolines in almost quantitative yield and with des >98%. (g) The sulfinyl group is responsible for the complete control of the n-facial selectivity in all these reactions.75 The Rh(II)-catalysed intramolecular 1,3-dipolar cycloaddition reaction of diazoamides (57) with alkenyl and heteroaromatic n -bonds yields pen-tacyclic compounds (59), via the ylide (58), in good to excellent yields and in a (g) stereocontrolled manner (Scheme 15).76... 

Discrepancies between different researchers derive from the character inter-or intramolecular of the interactions presumably controlling the reactive conformation. Thus, in most of the cases, the population of the different rotamers in the sulfinylated substrate (only governed by intramolecular interactions) is the only factor considered for explaining the observed 7r-facial selectivity. This explanation (static conformational polarization) was formulated by Koizumi and used by many authors to justify the behavior of vinyl sulfoxides acting as dienophiles and dipolarophiles. A second explanation assumes that the interactions of the two reagents in the transition states determine a different reactivity of the rotamers around the C-S bond. This intermolecular factor can become the most important one in the control of the 7r-facial selectivity of the cycloadditions, and therefore the tendency expected from conformational stability criteria was not observed in those cases where the most reactive conformation is not the most populated one. This dynamic conformational polarization has been used just to explain some of the results obtained for sulfinyl quinones and sulfinyl dienes (unexplainable with the above model) but it can be applied to many other cases. 

The photochemical cycloaddition of ethene to the bis-butenolides (20) has been examined in an attempt to establish the influence of the ether-protecting groups of the diol system. Generally only two adducts are formed as can be seen from the results shown for the appropriate structures. The most effective ether protecting group is the trimethylsilyl function and here the facial selectivity yields predominantly the anti,anti adduct (21). With the unprotected systems (20, R = H), there is virtually no selectivity and in this case the three adducts (21), (22) and (23) are formed. Irradiation of the butenolides (20a) and (20b) in the absence of ethene leads to intramolecular hydrogen abstraction (a Norrish Type II process) with the formation of the products (24a) and (24b) in 79% and 76%, respectively. 

Another diastereoselective intramolecular Diels-Alder reaction of furan was studied by Keay wherein the methyl group in the tether of (—)—12 directed the facial selectivity of the cycloaddition. Equilibrating conditions using a catalytic amount of Lewis acid gave the tricyclic enone (—)-13, Eq. 10 [23]. 

Most applications of the intramolecular Diels-Alder reaction use 1-substituted butadienes and these reactions often form a key step in the synthesis of polycyclic natural products. Substituents in the connecting chain may influence the facial selectivity of the cycloaddition reaction, as well as the endo. exo selectivity. For example, in a synthesis of the antibiotic indanomycin, the triene 83 gave, on heating. 

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