Ether cleavage pattern

The structural features of this group are summarized as follows (1) possession of an acetal or a hemiacetal ether linkage between C-8 and C-10, and (2) either absence of a substituent or presence of a hydroxyl group or ester moiety at C-6. Because a large number of hasubanan alkaloids follow this cleavage pattern, the metaphanine-type cleavage may be one of the primary pattern for all hasubanan alkaloids (76). 

A clue to the structure of ipecoside was obtained from the NMR and mass spectra of the glycoalkaloid and many of its derivatives. The NMR spectrum of ipecoside hexatrimethylsilyl ether showed the presence of two aromatic protons, four olefinic protons, one methoxycarbonyl, and one N-acetyl function. In the mass spectrum of ipecoside no molecular ion could be detected, but important characteristic peaks appeared at m/e 220,206,178, 164, and 43, assigned to the cleavage pattern of substituted IV-acetyl-l-alkyl-l,2,3,4-tetrahydroisoquinolines. 

The clear cleavage pattern emerges the tertiary alkyl group is converted more readily into the corresponding bromide than the secondary one, and the latter more readily than a primary group. Consequently, f-butyl-n-butyl ether gives exclusively f-butylbromide, whereas sec-butyl-n-butyl ether leads only to sec-butylbromide. Isobutyl-n-butyl ether yields predominantly n-butylbromide. 

Each substituted benzyl ether has a different oxidation potential (1.45 V for the DMB-OR, and 1.78 V for the PMB-OR), so each methoxy substitution pattern results in different rates of ether cleavage. This means that the DMB group can be removed in the presence of a PMB ether with high selectivity (eq 3). It has also been shown that other methoxybenzyl ethers react at widely differing rates. For example, the reaction time for the DMB ether was <20 min (86% yield of alcohol), and the 2,6-dimethoxy isomer required 27.5 h (80% yield) (eq 4). Other substitution patterns give reaction times between these two extremes. 

As with long-chain ethers, the hydrocarbon pattern may dominate the spectrum of long-chain sulfides the CnH2n peaks seem especially prominent. In branched-chain sulfides, cleavage at the branch may reduce the relative intensity of the characteristic sulfide peaks. 

The synthesis followed this pattern with the ethers 24 being made immediately after the reduction of 25 and the esters made with diazomethane CH2N2 after oxidative cleavage. 

C—O bond cleavage with the charge remaining on the alkyl fragment. The spectrum of long-chain ethers becomes dominated by the hydrocarbon pattern. 

Several of the reactivity patterns that were observed in the development of the oxidative carbon-carbon bond forming reactions were evident in the ETIC reaction of compound 56 (Scheme 3.19). Two homobenzylic ethers that potentially could fragment are present in this substrate. Cleavage in the presence of CAN was observed exclusively at the site that contains the geminal methyl groups, however, resulting in the formation of tetrahydropyran 57. This cyclization, which was used in the synthesis of a subunit of the cytotoxin apicularen demonstrated that fragmentations can be... 

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