Transition state oxetane

For oxetane formation from formaldehyde and ethylene, we should consider the following four transition states and intermediates for the reaction<181) ... 

Kinetic data on the influence of the reaction temperature on the enantioselectivity using chiral bases and prochiral alkenes revealed a nonlinearity of the modified Eyring plot [16]. The observed change in the linearity and the existence of an inversion point indicated that two different transition states are involved, inconsistent with a concerted [3+2] mechanism. Sharpless therefore renewed the postulate of a reversibly formed oxetane intermediate followed by irreversible rearrangement to the product. 

The rates of nucleophilic additions to adamantanone have been studied in an attempt to determine the structure of the transition states of nucleophilic additions to carbonyl compounds in general. The kinetic analysis suggests that the transition states of borohydride reductions of ketones are product-like while for bisulfite additions the transition states are reactant-like 367). A similar analysis 36 ) of data obtained for photo-initiated oxetane formation (trans-dicyanoethylene + carbonyl compound) 3681 indicates a reactant-like transition state. 

The influence of substituents on the energetics of the uncatalyzed Mukaiyama aldol reaction was studied using ab initio molecular orbital calculations at the G3(MP2) level <2005JOC124>. For the reaction between formaldehyde and trihydrosilyl enol ether, a concerted pathway via a six-membered transition state was favored over a stepwise pathway and an oxetane intermediate. 

The malic acid derivative 12 reacted with benzaldehyde to yield the oxetanes 13a,b with a diastereomeric excess of 80% (Scheme 4) [10]. It should also be mentioned that the regioselectivity and the exo/endo selectivity are complete. The favored formation of 13a is explained by the dominant conformation depicted in A, B. The syn approach of benzaldehyde excited in the 3n,7r state with respect to the alkoxy substituent (transition state A) is hindered by electrostatic repulsion between the substituent and the carbonyl group having a reversed polarity in the excited state. The addition of benzophenone to the furan derivative 14 was stereospecific [11]. In this case, however, the attack of the 3n,TT excited ketone occurred in a syn manner with respect to the hydroxy function to yield 15. The conformation indicated in the transition state C was supported by calculations. 

A unique condensation is observed between 1,3-dimethoxy-l-trimethylsiloxybuta-diene (35) and cinnamaldehyde (36) producing the acyclic adduct 37 in 72 % yield when catalyzed by Ag(fod) (Sch. 8). In contrast, when Eu(fod)3 or Yb(fod)3 is used as the catalyst, a hetero-Diels-Alder reaction takes place exclusively [17]. The acyclic adduct 37 is believed to be formed by a [2 -i- 2] cycloaddition via an oxetane rather than through a six-membered ring transition state (Mukaiyama aldol type reaction). 

The calculations of the transition states led to the following predictions concerning the kinetically most favorable reactions pathways [140]. The reaction of ketene with OSO4 should proceed via [3+2] addition across the C=C bond. The [2+2] addition reactions of all LReOj species to ketene have lower activation energies than the [3+2] addition. These were the first examples where calculations showed that the [2+2] addition of a metal oxide to a C=C bond has a lower barrier than the [3+2] addition. For Re07 and (HjPNlReOj it was found that the [2+2] addition to the C=0 bond is kinetically even more favorable than the addition to the C=C bond. However, the calculation predicted that the [2+2] addition of MeReOj, CpReOj and Cp ReOj should proceed via [2+2] addition across the C=C bond yielding the metalla-2-oxetane. 

Whether the oxetane or the tetrahydrofuran is formed depends on which end of the iodonium ion is attacked by the OH group. In terms of Baldwin s rules, oxetane formation is a simple A-exo-tet reaction and is favoured. The THF formation is sUghtly more complicated. It is a 5-exo-tet as far as the Sn2 reaction is concerned, but in the transition state the nucleophile, the carbon atom under attack and the leaving group are also all in the same six-membered ring—there is disfavoured 6-endo-tet character. It is very difficult... 

The activation energy of polymerizations of oxetane monomers is higher that that of tetrahy-drofuran (see next section). This indicates that the orientation of the cyclic oxonium ion and the monomer is looser in the Siv2 transition state" ... 

Hi as exemplified be ( )-361 with axial C7-H which destabilize transition state leading to the diastereomer of ester 360. Calculations also indicate attractive interactions of Ci of the ketene acetals with the hydrogens of the ring fused oxetane as depicted in arrangement ( )-362. 

According to the scheme, formaldehyde dimers preliminary form the corresponding 71-cations (2b-5b) with alkenes (2a-5a), which are isomer-ized into a-cations (2i-5i). These a-cations are transformed through the transition states (2j-5j) into oxetanes (2k-5k). The calculated values of the thermodynamic parameters are represented in Table 11.3. 

The transition states of the oxetane formation reaction are shown in Fig. 11.7. 

For a smooth transition from the previous section, we will continue by discussing the work of Sun and coworkers, who reported their efforts on the application of a new directing group in an organocatalyzed MCR in 2013 [25]. The rarely used oxetane proved to be the ideal hydrogen-bond acceptor that supports the formation of the desired transition state. The previously used ethers already exhibited some desired directing effects and delivered perfect diastereoselectivity (>95 5 dr), but proved ineffective for enantioselectivity (<5% ee). By employing the oxetane, however, the envisioned aza-Diels-Alder reaction proceeded as intended with excellent diastereo (>99 1 dr) and enantioselectivity (99% ee). The proposed transition state of this desymmetrization clarifies the selectivity of the reaction the chiral phosphoric acid allows the amine to approach only from the front face (Scheme 14.10). 

Another photoreaction between ketones and olefins or dienes, which has often been connected to the involvement of exciplexes, is the Patemo-Biichi reaction [4,5], i.e., the photocycloaddition of C=C double bonds to carbonyl C=0 bonds under formation of oxetanes [17,78,207-217], Especially for electron-rich olefins such as ethyl vinyl ether or 1,2-diethoxyethylene, intermediary exciplexes have often been postulated [212], with the consequence of a diminished legioselectivity and stereospecificity for oxetane formation. On the other hand, electron-deficient olefins such as a,P-unsaturated nitriles react with a high legioselectivity and stereospedlicity due to a well defined transition state, which is based on the electronic leqniranents of n,7t -excited ketones [17]. 

The lowest-lying excited state of ketones most often corresponds to a o 7t c=o transition. The maximum of this band is around 280 nm with simple aldehydes or ketones and is shifted to the red for conjugated or aryl derivatives. As hinted above, the unpaired electron on the hq orbital gives to these states electrophilic properties similar to those of alkoxy radicals, and indeed the observed chemistry is similar in the two cases. Typical reactions are a-fragmentation, inter- or intramolecular (from the easily accessible y position) hydrogen abstraction and attack of alkenes (finally resulting in a formal 2h-2 cycloaddition to give an oxetane, the Paterno-Btichi reaction). 

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