Transition states ether formation

In a more recent study, Hillier placed two water molecules around the oxygen of allyl vinyl ether and its transition state for formation of 4-pentenal in an MP2/RHF/6-31G calculation [56]. When the SCRF model was used, no net decrease in activation free energy was obtained at the /= 1 level (atomic monopoles) and lack of convergence accompanied attempts to use higher terms in the multipole expansion. However, the PCM model provided a net energy decrease of 4.3kcalmol, which corresponds favorably to experiment. Somewhat disconcerting, however, were the calculated kinetic isotope effects = 1.149 and =0.919), which differed from the exper-... 

The smooth intramolecular nucleophilic displacement of biphenyl carboxylic acids leading to benzocoumarins (See Section II.A.) inspired also investigation of the behavior of similar diphenyl ether, diphenyl sulfide and A-methyldiphenyl amine derivatives 458 under similar conditions. However, all these attempts to achieve cyclization to tricyclic compounds 459 were unsuccessful, probably due to the unfavorable stereochemistry for the formation of the required seven-mem-bered transition states and also to the presence of the deactivating bridge groups X (Eq. 42) [68JCS(C)1030]. 

The Lewis acid-catalyzed reaction of nitrone 21 with ethyl vinyl ether 22 (Scheme 8.8) was also investigated for BH3 and AlMe3 coordinated to 21 [32]. The presence of BH3 decreases the activation energy for the formation of 23 by 3.1 and 4.5 kcal mol to 9.6 kcal mol for the exoselective reaction and 11.6 kcal-mol for the endo-selective reaction, respectively, while the activation energy for the formation of 24 increases by >1.4 kcal mol , compared to those for the uncatalyzed reaction. The transition-state structure for the BH3-exo-selective 1,3-dipolar cycloaddition reaction of nitrone 21 with ethyl vinyl ether 22 is shown in Fig. 8.19. 

The successful implementation of this strategy is shown in Scheme 4. In the central double cyclization step, the combined action of palladium(n) acetate (10 mol %), triphenylphosphine (20 mol %), and silver carbonate (2 equiv.) on trienyl iodide 16 in refluxing THF results in the formation of tricycle 20 (ca. 83 % yield). Compound 20 is the only product formed in this spectacular transformation. It is noteworthy that the stereochemical course of the initial insertion (see 17—>18) is guided by an equatorially disposed /-butyldimethylsilyl ether at C-6 in a transition state having a preferred eclipsed orientation of the C-Pd a bond and the exocyclic double bond (see 17). Insertion of the trisubstituted cycloheptene double bond into the C-Pd bond in 18 then gives a new organopal-... 

The lower diastereoselectivity found with aldehyde 15 (R = CH3) can be explained by the steric influence of the two methyl substituents in close vicinity to the stereogenic center, which probably diminishes the ability of the ether oxygen to coordinate. In contrast, a significant difference in the diastereoselectivity was found in the additions of phenyllithium and phenylmagnesium bromide to isopropylidene glyceraldehyde (17)58 (see also Section 1.3.1.3.6.). Presumably the diastereo-sclcctivity of the phenyllithium addition is determined by the ratio of chelation-controlled to nonchelation-controlled attack of the nucleophile, whereas in the case of phenylmagnesium bromide additional chelation with the / -ether oxygen may occur. Formation of the -chelate 19 stabilizes the Felkin-Anh transition state and therefore increases the proportion of the anZz -diastereomeric addition product. 

Reaction of 2a with Cl2BCH2SiMe3 yields the compound 3a [18]. When the symmetrically substituted 3a is reacted with lithium in diethyl ether, the unsymmetri-cally substituted folded 4b [18] is obtained (Scheme 3.2-3). Formation of 4b can be explained by a rapid isomerization of the first formed 4a via the distorted tetrahedral transition state 5a. 

Thus far, in the alkaloid series discussed, the nitrogen atom has always been part of the core of the alkaloid strucmre, rather than acting in a dipolarophilic manner in the cycloaddition of the carbonyl ylide. Recently, Padwa et al. (117) addressed this deficiency by conducting model studies to synthesize the core of ribasine, an alkaloid containing the indanobenzazepine skeleton with a bridging ether moiety (Scheme 4.57). Padwa found that indeed it was possible to use a C = N 7i-bond as the dipolarophile. In the first generation, a substimted benzylidene imine (219) was added after formation of the putative carbonyl ylide from diazoketone 218. The result was formation of both the endo and exo adduct with the endo adduct favored in an 8 1 ratio. This indicates that the endo transition state was shghtly favored as dictated by symmetry controlled HOMO—LUMO interactions. 

The transition state of singlet carbene cycloaddition to alkenes involves an electrophilic approach of the vacant p orbital to the n bond of alkenes. By contrast, the first step of the triplet addition process may involve the in-plane a orbital of the carbene. As in the case of C—H insertion (see Section 5.1), the difference in the transition structure between the singlet and triplet cycloaddition becomes important in the intramolecular process, especially when approach to a double bond is restricted by ring strain. Direct photolysis of ( )-2-(2-butenyl)phenyldiazomethane (99) in the presence of methanol gives l-ethenyl-l,la,6,6fl-tetrahydrocycloprop [fljindene [100, 29%, (E/Z)= 10 1] and l-(2-butenyl)-2-(methoxymethyl)benzene (101, 67%). Triplet-sensitized photolysis results in a marked increase in the indene (52%, EjZ) = 1.3.T) at the expense of the ether formation (4%) (Scheme 9.30). On the other hand, direct photolysis of phenyldiazomethane in an equimolar mixture of... 

---