Hemiacetal cleavage

Kinetic data on acetal formation and cleavage in alcohols are scarce although kinetic and thermodynamic data in the same experimental conditions are of great interest (Davis et al., 1975). It should be noted that under these conditions inequality (53) is inverted and that, therefore, the rate-limiting step corresponds to water addition to an alkoxycarbenium ion (Step 3) or hemiacetal cleavage (Step 4). Recent data by El-Alaoui (1979) on forward and reverse rates are in agreement with those expected the acetal formation rate is independent of water concentration for a series of substituted acetophenones. 

Acetals (s. a. Hemiacetals) cleavage 31, 61 formation under non-acidic conditions 31, 216... 

This is supported by the observation that 0-labelled alcohol is cleaved to unlabelled /-butanol. Wiberg has given other examples of this type of cleavage, and has dealt with other complications such as further oxidation of products, formation of hemiacetals, etc. 

The reaction mechanism is based on protonation of the hydroxyl moiety, rearrangement of the phenyl group and simultaneous cleavage of water, creating a carbocation as intermediate [135]. This cation is hydroxylated by water. Thereby, an unstable hemiacetal is formed that splits into two molecules, phenol and water. 

O-acetylophiocarpine (381) with ethyl chloroformate afforded the C-8—N cleaved urethane 382 in quantitative yield. Sequential treatment of 382 with silver nitrate, PCC, sodium hydroxide, and p-toluenesulfonic acid in ethanol furnished acetal 384, which was reduced with lithium aluminum hydride followed by hydrolysis to afford the hemiacetal 385. Oxidation of 385 with PCC provided (+ )-a-hydrastine (369). Similar treatment of O-acetylepi-ophiocarpine (386) afforded ( )-/J-hydrastine (368) however, in this case, C—N bond cleavage of 386 with ethyl chloroformate proceeded without regioselectivity. 

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). 

Denmark and coworkers have found that methylaluminum bis (2,6-di-tert-butyl-4-methyl-phenoxide) (MAD) or methylaluminum bis(2,6-diphenylphenoxide) (MAPh) is effective as the Lewis acid promoter for cycloaddition of 2,2-disubstituted 1-nitroalkenes (Eq. 8.100).158 Other Lewis acids such as SnCl4, TiCl4, and TiCl2(Oi-Pr)2 fail to promote the cycloaddition of 2,2-disubstituted 1-nitroalkenes. The products are converted into 3,3-disubstituted pyrrolidines via hydrogenolysis.158 Reductive cleavage of N-0 bonds produces oxime hemiacetals, which are further reduced to amido aldehydes and finally to pyrrolidines. This reaction provides a useful synthetic method for pyrrolidines, which is discussed later. 

To avoid the retro-Diels-Alder reaction, 56 was dihydroxylated prior to the introduction of the bromine atom (57). Removal of the acetonide group followed by cleavage of the diol afforded a bis-hemiacetal. Selective reduction of the less-hindered hemiacetal group gave 58. The remaining hemiacetal was protected, and the ketone was converted to an enol triflate, thus concluding the synthesis of the electrophilic coupling component 51. 

A modification of the Hantzsch synthesis of thiazoles has been reported. The reaction of alkoxyoxiranes 16 with A-arylthioureas 17 affords thiazoles such as 20. The mechanism involves the initial P-cleavage of the oxirane to give the hemiacetal... 

Oxidative cleavage of a-hydroxycycloalkan-ones, (11), in MeOH-LiCl04 at a Pt anode in a divided cell, [13, 20] has been suggested to take place via the hemiacetal, (12), formed in situ by EGA catalysis [13], Scheme 6. 

The proposed mechanism for the photochemical cleavage of nBn ethers (see Scheme 3) involves a n tt transition of the nitrogroup and an intramolecular, benzylic hydrogen abstraction by the excited nitro group. Rearrangement leads to a hemiacetal that decomposes to a free alcohol and to 2-nitrosobenzaldehyde that undergoes further thermal and photochemical reactions. 

The full paper of Tietze s biogenetic-type synthesis of secologanin aglucone methyl ether and sweroside aglucone methyl ether has been published (Vol. 5, p. 18), and a second paper independently reports in full the rapid enzymic cleavage of secologanin to the bicyclic hemiacetal previously described by R. T. Brown (Vol. 7, p. 27) longer reaction times result in the formation of (146). ... 

---