Protonated diol epoxides

Model computational studies aimed at understanding structure-reactivity relationships and substituent effects on carbocation stability for aza-PAHs derivatives were performed by density functional theory (DFT). Comparisons were made with the biological activity data when available. Protonation of the epoxides and diol epoxides, and subsequent epoxide ring opening reactions were analyzed for several families of compounds. Bay-region carbocations were formed via the O-protonated epoxides in barrierless processes. Relative carbocation stabilities were determined in the gas phase and in water as solvent (by the PCM method). 

Fig. 10.14. Reactivity ofdiol epoxides (Nu = H20, HCT, or another nucleophile), a) Hydrolytic reaction of diol epoxides to tetrols. b) Internal H-bonding in diol epoxides with syw-config-uration and rendering the distal C-atom more electrophilic (modified from [104]). c) General representation of proton-catalyzed (A-H = H+), general acid catalyzed (A-H = acid), or intra-molecularly catalyzed (A-H = syn-OW group) activation of the distal C-atom toward... 

Further studies that demonstrate that hydration of bay-region diol epoxides under acidic conditions can occur by general acid catalysis in addition to proton catalysis have expanded our understanding of their reactivity. General acid catalyzed hydration involves H-bonding of the epoxide O-atom by the acid catalyst, followed by nucleophilic attack of the distal C-atom by H20/H0 [108][109],... 

Most epoxides are easily isolated as stable products if the solution is not too acidic. Any moderately strong acid protonates the epoxide, however. Water attacks the pro-tonated epoxide, opening the ring and forming a 1,2-diol, commonly called a glycol. 

In 2001, ab initio, density-functional and semiempirical calculations on the reactivity of polycyclic aromatic hydrocarbon episulfides 10-22 were reported. Episulfides are predicted to open more easily than the corresponding 0-protonated derivatives, epoxides and diol epoxides <2001HCA3588>. Calculation results for the episulfide ring opening of the j -protonated compounds are shown in Table 1. 

A novel ring-opening reaction of oxirans, catalysed by copper and pyridine, generates c/s-diols under mild conditions. The bicyclic epoxides (186 = 1 or 2) yield (187 n = 1) (95%) and (187 = 2) (85%) in neutral, phosphate-buffered, solution. This type of reaction may have some relevance to the metabolic pathways for fused aromatic compounds, which are thought to proceed via arene oxides and diol epoxides. The catalyst system may be used to add OH", Cr, or MeO regiospecifically to the benzylic centre of indene oxide, with proton addition to the oxygen atom of oxiran. 

The cleavage reaction occurs in three steps O protonation of the epoxide, Sn2 nucleophilic attack on the protonated epoxide, and deprotonation of the ring-opened product. Draw the complete mechanism. How many intermediates are there Which step determines diol stereochemistry ... 

Epoxides are cleaved by treatment with acid just as other ethers are, but under much milder conditions because of ring strain. As we saw in Section 7.8, dilute aqueous acid at room temperature is sufficient to cause the hydrolysis of epoxides to 1,2-diols, also called vicinal glycols. (The word vicinal means "adjacent/ and a glycol is a diol.) The epoxide cleavage takes place by SK2-like backside attack of a nucleophile on the protonated epoxide, giving a trans- 1,2-dio) as product. 

Some such pathway is necessary to account for the migration of oxygen that is found. It may involve a protonated epoxide, a 1,2-diol, or simply a 1,2 shift of an OH group. 

Initial attack by base on (34) yields the alkoxide anion (36), internal attack by this ROe then yields the epoxide (37) with inversion of configuration at C (these cyclic intermediates can actually be isolated in many cases) this carbon atomf, in turn, undergoes ordinary SN2 attack by eOH, with a second inversion of configuration at C. Finally, this second alkoxide anion (38) abstracts a proton from the solvent to yield the product 1,2-diol (35) with the same configuration as the starting material (34). This apparent retention of configuration has, however, been brought about by two successive inversions. 

Scheme 4-21 shows the preparation of L-threitol and L-erythritol.38 Epoxy alcohols (2J ,3iS)-61 and (2S,3/ )-61. generated by asymmetric epoxidation, are exposed to sodium benzenethiolate and sodium hydroxide in a protonic solvent to undergo base-catalyzed rearrangement, yielding the threo-diol 62 and erythro-diol 63, which can then be converted to the corresponding tetraacetate of l-threitol 67 and L-erythritol 69 through subsequent transformations. 

Fig. 10.11. Chemical mechanisms in the hydrolysis ofK-region epoxides. Pathway a characteristic proton-catalyzed hydrolysis under acidic conditions Pathway b nucleophilic hydrolysis by H2C) Pathway c HO"-catalyzed hydrolysis under basic conditions. Pathways b and c form the trans-diol. In the case of Pathway a, partial configurational inversion may occur at the carbonium ion, resulting in a mixture of the trans- and cw-diols. 

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