Stereoselectivity electrocyclic

In an extension to the above methodology, a sequential 1,2-addition, dehydration, and in situ ring closure via a 67t-electron electrocyclic cyclization has been described in the context of the pharmacologically relevant natural products warfarin A, the arisugacins, merulidial, and isovelleral (Scheme 20) <2005CAR1287>. Carbohydrate-derived a,3-unsaturated enals were coupled with 4-hydroxycoumarin 188 and 4-hydroxy-6-methylpyran-2//-one 191 in the presence of proline catalysts to provide pyrone-annulated products of types 190 and 192. Stereoselective electrocyclic ring closure was observed only when hydroxyl functionality (at any of R -k ) on the enal was acyl protected. 

A stereoselective electrocyclization developed for the synthesis of reserpine results from a stereocentre six atoms away from the newly fornoing chiral centre that is responsible for the diastereoselectivity of the ring closure. The presence of allylic strain in the disfavoured transition state results in the torquoselective ring closure (Scheme 38). 

Thermal and photochemical electrocyclic reactions are particularly useful in the synthesis of alkaloids (W. Oppolzer, 1973,1978 B K. Wiesner, 1968). A high degree of regio- and stereoselectivity can be reached, if cyclic olefin or enamine components are used in ene reactions or photochemical [2 + 2]cycloadditions. 

Strategies based on two consecutive specific reactions or the so-called "tandem methodologies" very useful for the synthesis of polycyclic compounds. Classical examples of such a strategy are the "Robinson annulation" which involves the "tandem Michael/aldol condensation" [32] and the "tandem cyclobutene electrocyclic opening/Diels-Alder addition" [33] so useful in the synthesis of steroids. To cite a few new methodologies developed more recently we may refer to the stereoselective "tandem Mannich/Michael reaction" for the synthesis of piperidine alkaloids [34], the "tandem cycloaddition/radical cyclisation" [35] which allows a quick assembly of a variety of ring systems in a completely intramolecular manner or the "tandem anionic cyclisation approach" of polycarbocyclic compounds [36]. 

How can we account for the stereoselectivity of thermal electrocyclic reactions Our problem is to understand why it is that concerted 4n electro-cyclic rearrangements are conrotatory, whereas the corresponding 4n + 2 processes are disrotatory. From what has been said previously, we can expect that the conrotatory processes are related to the Mobius molecular orbitals and the disrotatory processes are related to Hiickel molecular orbitals. Let us see why this is so. Consider the electrocyclic interconversion of a 1,3-diene and a cyclobutene. In this case, the Hiickel transition state one having an... 

Stereoselectivity of some methyl substitution on the alkenyl group was examined by the series 228 [277] (Scheme 66). Irradiation of methanol solutions of 228 at >290 nm resulted in the clean conversion of each reactant into a mixture of two diastereomers of 231. The 231 are then converted thermally (25-100°C) to equilibrium mixtures with 229 and 230. High diastereomeric excesses (R2 is trans to R1 or R3) in 229-231 are always observed. This fact indicates that the photoin-duced electrocyclization to a cyclobutene 231 of one diene unit of the bicy-clo[6.3.0]undecatriene intermediate 230 undergoes disrotatory photoclosure in only one of two possible directions. 

The state-symmetry correlation also indicates that electrocyclic radical interconversion favors a conrotatory path from the first excited state and a disrotatory path from the second excited state. Because of the proximity of the energy levels and the violations of the noncrossing rule, it is probable that the excited state process will not be highly stereoselective. The same detailed considerations must be applied to the five-atom five-electron system and yield the results given in Table 1. Differences between the stereochemical predictions of Table 1 and those of others (Woodward and Hoffmann, 1965a Fukui and Fujimoto, 1966b Zimmerman, 1966) tend to be limited to the excited-state reactions of odd-atom radicals. 

Not all electrocyclic reactions are stereoselective. It turns out that none of the three of the possible interconversions between triplet cyclopropylidene and allene should show SS, according to an analysis given by Borden (1967). 

This reactivity proved to be a general process, providing the unique products in moderate yields following cyclopropanation and immediate treatment with silver tetrafluoroborate. These structures revealed that a cascade sequence was proceeding stereoselectively in every case to furnish a single product as the result of conrotatory 4jt electrocyclization, electrophilic aromatic substitution at the least hindered position on the arene moiety (para to the MeO) in favor of six-membered ring formation, and desilylation with protonation from the exo face of the bicyclic product. Dehydrochlorination to form a second cationic intermediate did not occur in this case, due to structural restrictions imposed by the bridged architecture of 81. 

It is clear, nonetheless, that successful dearomatising cyclisations are not confined to systems which can undergo electrocyclic ring closure 456 for example cyclises to 457, which may be protonated or alkylated stereoselectively.201 Without the oxazoline substituent, similar reactions lead to rearomatisation. 

Another gain in diversity is achieved by the combination of these cross couplings with uncatalyzed reactions. Because of their oligounsaturated character, the coupling products are obviously well suited for subsequent peri-cyclic reactions leading to additional cyclizations. These atom-efficient processes are especially attractive since they typically proceed with high chemo-, regio- and stereoselectivity [18]. This review is intended to cover Heck reactions and related palladium-catalyzed processes followed by Diels-Alder reactions, 1,3-dipolar cycloadditions or 6 -electrocyclizations. 

The concept of torquoselectivity is now accepted as an extension of the Woodward-Hoffman rules. It has been used as a guide for synthetic chemists to prepare the appropriate stereoisomer. Examples include Danishefsky s exploitation of the stereoselective ring opening of fran5 -l,2-disiloxybenzocyclobutenes 133 to prepare idarubicin, Paquette s use of the electrocyclization of 134 that ultimately leads to a very efficient synthesis of pentalene, and Murakami s ... 

Evanseck, J. D. Thomas IV, B. E. Spelhneyer, D. C. Houk, K. N. Transition structures of thermally allowed disrotatoiy electrocyclizations. The prediction of stereoselective substituent effects in six-electron pericyclic reactions, J. Org. Chem. 1995, 60,7134-7141. 

Substrate-Induced Stereoselectivity by Stereogenic Centers Outside the Electrocyclic Arena... 

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