Biradical reactions stereoselectivity

Similarly, ab initio calculations on the thermal reaction of propene forming methyl-cyclopentane suggested a three-step biradical reaction with 1,4-biradical and 1,5-biradical as intermediates. Quantum-chemical calculations have been carried out for the cyclization of the neocarzinostatin chromophore cyclonona-l,2,3,5-tetraen-7-yne to 1,5-didehydroindene biradical. The degree of stereoselectivity of the Diels-Alder reaction of 2-methylfuran and maleic acid in water has been found to reduce significantly in the presence of heavy atoms. Taking into account the relatively low concentration (3.5-7 m) of heavy-atoms, and the rapid fall off of the heavy-atom effect with distance, these results show that a large portion of the Diels-Alder reaction occurs via diradical intermediates. " ... 

Like (5-alkoxy ketones, (5-amido ketones also undergo photoinduced 8-hydrogen abstraction to give proline derivatives (in <50% chemical yield) (Scheme 6.126).967 The reaction stereoselectivity depends on the biradical cyclization rate, which competes with conformational changes. Whereas singlet biradicals couple without reaching conformational equilibrium, the triplet biradicals allow bond rotation before the ring forms. 

Careful application of the three simple postulates listed above can yield insight into the mechanism and stereochemistry of biradical reactions as complex as the thermal dimerization of cis, irons-1,5-cyclooctadiene [26] or the isomerization of allyl-substituted cyclopropanes via internal [2 + 2]-cycloaddition [27]. An attempt to do so here would take us too far afield, in view of the ease with which biradical intermediates interconvert. Instead let us move on to the considerably more stereoselective cycloaddition of reactant pairs with complementary polarity, that proceeds stepwise along a zwitterionic pathway. [23]... 

Many mechanisms had been proposed in the past to rationalize this selectivity (tri-oxanes, perepoxide, exciplex, dipolar or biradical intermediates) however, it is now generally accepted that the reaction proceeds through an intermediate exciplex which has the structural requirements of a perepoxide. This assumption is supported by (a) the lack of stereoselectivity in the reactions with chiral oxazolines and tiglic acid esters (b) the comparison of the diastereoselectivity of dialkyl substituted acrylic esters with structurally similar non-functionalized aUtenes (c) the intermolecular isotope effects in the photooxygenation of methyl tiglate and (d) the solvent effects on regioselectivity. ... 

Pericyclic reactions are unimolecular, concerted, uncatalyzed transformations. They take place in a highly stereoselective manner governed by symmetry proper-ties of interacting orbitals. - Characteristic of all these rearrangements is that they are reversible and may be effected thermally or photochemically. The compounds in equilibrium are usually interconverted through a cyclic transition state,224 although biradical mechanisms may also be operative. A few characteristic examples of pericyclic rearrangements relevant to hydrocarbon isomerizations are presented here. 

When an alkyl or aryl ketone, or an aryl aldehyde, reacts with an alkyl-substituted ethylene, or with an electron-rich alkene such as a vinyl ether, the mechanism involves attack by the (n,n triplet state of the ketone on ground-state alkene to generate a 1,4-biradical that subsequently cyclizes. The orientation of addition is in keeping with this proposal, since the major product is formed by way of the more stable of the possible biradicals, as seen for benzophenone and 2-melhylpropene (4.64). As would be expected for a triplet-state reaction, the stereoselectivity is low, and benzophenone gives the same mixture of stereoisomers when it reacts with either trans or... 

If nitrogen is eliminated from a cyclic azoalkane by irradiation, the initially formed biradical may react by internal combination to form a smaller-ring cycloalkane. On direct irradiation this is often a highly stereoselective process (5-21), although mixtures of isomers are generally formed when triplet sensitization operates. This reaction... 

Photoinduced cyclizations of phenyl triphenylsilyl thioketone (156) with cis- and fraws-l,2-dichloroethene give a mixture of silyl thietanes 157 and 158 in a regio- and stereoselective manner (equation 66)207. These reactions involving biradical intermediates and ring closure are governed by the steric effect. The steric hindrance between the Ph3Si group and the vicinal chlorine atom ensures their trans relationship in the thietane products. 

The best results can be obtained considering the energy of the triplet biradical intermediates (Fig. 3.19). Calculations on these biradical intermediates showed that the first (the precursor of the observed product) was more stable than the other by 0.73 kcal mol-1. Furthermore, the first and the second possible biradical intermediate in the reaction of the ester of (S)-2-methyl-l-butanol and differed by only 0.02 kcal mol-1, in agreement with the observed no stereoselectivity of the reaction. Finally, the first biradical intermediate in the reaction of 8-phenyl-menthol ester proved to be more stable than the other one by 21.9 kcal mol-1. This result is also in agreement with the observed high diastereoisomeric excess. 

The regioselectivity of intramolecular [2 + 2]-photocydoaddition reactions is predictable if five-membered ring formation is possible in the formation of biradicals of type C or C (rule of five, vide supra). If five-membered ring formation is not feasible, then six-membered rings are most readily formed. The facial diastereo-selectivity is efficiently controlled by a stereogenic center in the cyclopentenone if the intramolecular alkene is attached via a tether to this stereogenic center. The key step 16 —> 17 in the stereoselective synthesis of (—)-incarvilline (18) illustrates the point (Scheme 6.7) [28]. The side chain attached to C-4 in the cyclopentenone 16 carries the terminal alkene, which reacts intramolecularly with perfect regio- and diastereoselectivity to cyclobutane 17. 

In general, the stereoelectronic influence of substituents in [2 + 2]-photocycload-dition reactions is minor, and the preferred ground-state conformation often accounts for the formation of the major diastereoisomer. Inspection of molecular models and force field calculations provide a good picture of possible transition states leading via 1,4-biradicals to cyclobutane products. The total synthesis of (+)-guanacastepene represents another recent example for the use of stereoselective intramolecular cyclopentenone-olefin photocycloadditions in natural products synthesis [32]. 

As mentioned in Section 7.2, when the electron transfer reaction between electron-rich alkenes and excited carbonyl compounds is energetically favorable, the RI pair becomes an important intermediate in photochemical [2 + 2] cycloaddition reactions (Scheme 7.5). The regioselectivity of these reactions may differ from that observed for the PB reaction involving 1,4-triplet biradical intermediates. Typical examples of PB reactions with very electron-rich alkenes, ketene silyl acetals (Eox = 0.9 V vs SCE), have been reported (Scheme 7.11) [27]. Thus, 2-alkoxyoxetanes were selectively formed as a result of the PB reaction with benzaldehyde or benzophenone derivatives, whereas a selective formation of 3-alkoxyoxetanes was observed in less electron-rich alkenes (see Scheme 7.9). When p-methoxybenzalde-hyde was used in the photochemical reaction, the regioselectivity was less than that observed in the case of benzaldehyde. This dramatic decrease in regioselectivity provided evidence that the selective formation of 2-alkoxyoxetanes occurred via RI pair intermediates. It should be noted that the stereoselectivity is also completely different from that associated with triplet 1,4-biradicals (vide infra). 

However, this model can also be generalized to other cydicalkenes. The ISC reactive conformation of the intermediary triplet biradicals is important for stereoselectivity, as the rate constant for ISC, which is controlled by a spin-orbit-coupling (SOC) mechanism, is heavily dependent on the orientation of the two spin centers. The importance of the ISC process was reasonably proved by the low mdo-sclcctivity in PB reactions with naphthaldehydes or aliphatic aldehydes, in which the excited singlet states may react with alkenes [34]. The stereoselectivity observed in the PB... 

In the PB reaction using O.S-ketene silyl ether, oxetane formation was highly stereoselective (Scheme 7.18) [36]. Such stereoselectivity could be explained by the preferred conformation of the intermediary triplet 1,4-biradical for the ISC process. 

In the PB reaction of furan derivatives with benzaldehyde (as shown in Scheme 7.13), a site-random - but highly stereoselective - formation of exo-oxetanes was reported (Scheme 7.13) [15q,30]. The highly exo-selective formation of oxetanes was explained by the conformational stability of the intermediary triplet biradicals. The anomeric effect was proposed to play an important role in stabilization of the exo-isomer precursor (Scheme 7.20). Thus, the inside conformer which should... 

It should be noted that the stereoselectivity is also completely different from that associated with triplet 1,4-biradicals. Thus, a highly exo-selective formation ofbicyclic oxetanes was observed during PET-promoted PB reactions, whereas a highly endo-selective formation ofbicyclic oxetanes was reported for PB reactions that proceeded via triplet 1,4-biradicals (see Scheme 7.25). The competitive reaction pathway for electron-rich alkenes explained a notable solvent effect on the regioselectivity and stereoselectivity of the PB reaction of dihydrofuran (Scheme 7.15). Thus, an endo-selective formation of 3-alkoxyoxetane was observed when using benzene, whereas the exo-isomer of 2-alkoxyoxetane was detected as a product of the PB reaction in acetonitrile (Scheme 7.15). 

Bach and coworkers observed both regioselective and stereoselective oxetane formation during the PB reaction of acyclic vinyl ethers (Scheme 7.26) [15n], The stereoselectivity observed for such photochemical reactions cannot be explained using the Griesbeck Model, even though triplet, 14-biradicals were proposed as intermediates. Thus, the stereoselectivity was proposed to be largely dependent on product stability. 

In this chapter, recent developments in the regioselective, site-selective, and stereoselective preparation of oxetanes have been summarized. The relative nudeophilicity of the alkene carbons was seen to be important for regioselectivity, in addition to the well-known radical stability rule. Likewise, the three-dimensional structures of the triplet 1,4-biradicals were seen to play an important role in stereoselectivity. For photochemical reactions that proceed via radical ion pairs, the spin and charge distributions are crucial determinants of regioselectivity. It follows that the concepts used in selective oxetane synthesis should stimulate future investigations into the mechanistically and synthetically fascinating Paterno-Bitchi-type reactions. 

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