Activations hemiacetals

Reactions of Vinyl Ethers. Vinyl ethers undergo the typical reactions of activated carbon—carbon double bonds. A key reaction of VEs is acid-catalyzed hydrolysis to the corresponding alcohol and acetaldehyde, ie, addition of water followed by decomposition of the hemiacetal. Eor example, for MVE, the reaction is... 

The effect of a substituent may be substantially modified by fast, concurrent, reversible addition of the nucleophile to an electrophilic center in the substituent. Ortho- and para-CS.0 and pam-CN groups have been found by Miller and co-workers to have a much reduced activating effect on the displacement of halogen in 2-nitrohaloben-zenes with methoxide ion [reversible formation of hemiacetal (143) and imido ester anions (144)] than with azide ion (less interaction) or thiocyanate (little, if any, interaction). Formation of 0-acyl derivatives of 0x0 derivatives or of A-oxides, hydrogen bonding to these moieties, and ionization of substituents are other examples of reversible and often relatively complete modifications under reaction conditions. If the interaction is irreversible, such as hydrolysis of a... 

Reaction of 1,2-glycol systems, such as in the hemiacetal sesquiterpene 1751, with Me3SiCl/NaI in acetonitrile for 5 min at ambient temperature affords more than 80% of the corresponding olefin 1752 [15, 16] (Scheme 12.4). On reacting active methylene groups such as in ethyl acetoacetate or acetylacetone with benzal-dehyde in the presence of TCS14/Nal in acetonitrile, the intermediate unsaturated ketones 1753 and 1755 are reduced to ethyl 2-benzylacetoacetate 1754 [17] or 2-benzylacetylacetone 1756 [18] in 82% and 80% yield, respectively. 

The natural product panepophenanthrin (6/1-170), isolated in 2002 from the fermented broth of the mushroom strain Panus radus IFO 8994 [90], is the first example of an inhibitor of the ubiquitin-activating enzyme [91]. Retrosynthetic analysis based on a biomimetic analysis led to the conjugated diene 6/1-172 by a retro-Diels-Alder reaction via the hemiacetal 6/1-171. Further disconnections of 6/1-172 produces the vinyl stannane 6/1-173 and the vinyl bromide 6/1-174 [92]. 

Hemiacetal 25 [(3 ,4S,l E)-3,4-bis(r-butenyl)tetrahydro-2-furanol] is the male pheromone of the spined citrus bug (Biprorulus bibax). Scheme 38 summarizes Mori s synthesis of 25 [61]. Claisen rearrangement (A B) and lipase-catalyzed asymmetric acetylation [meso-C >(5S,6R)-D] were the two key steps of the synthesis. Further purification of D was executed at the stage of its crystalline derivative E. In this particular case, the unnatural (3S,4R,l E)-25 was as active as the natural (3R,4S,VE)-25. Accordingly, a more efficient synthesis of ( )-25 was achieved by the rearrangement of F, avoiding the use of toxic HMPA [62]. 

The total synthesis of optically active loganin (53) was accomplished by Partridge 25), who photolyzed a solution of the chiral acetate (60) and the ester (56). The intermediate (61) rearranged to the chiral hemiacetal (62), which served as a key compound in the synthesis of chiral loganin (53)15). 

Scheme 3.1 Electrophilic activation of hemiacetals for dehydrative glycosylation.

Silicon presents an attractive option among eledrophilic activating and dehydrating agents of hemiacetals because of the wide commercial availability of eledrophilic silicon sources. The two main classes of silicon electrophiles used, namely silyl halides and silyl sulfonates, have been demonstrated to promote a variety of glycosylations including some examples of oligosaccharide synthesis. 

In fact, other studies have shown that TMSOTf catalyzes the glycosylation of a silylated acceptor with a silylated hemiacetal donor [49]. Nudel man s procedure was applied to the synthesis [1-glucuronide 30, isolated in 57% yield. Kiyoi and Kondo have applied the TMSOTf activation protocol to protected L-fucose hemiacetal donors for glycopeptide synthesis and obtained glycopeptide fragment 31 in 74% yield (a p, 20 1) [50], Posner and Bull have developed a procedure that uses excess TMSOTf in the presence of molecular sieves (SYLOSIV A4) to synthesize various l.l -linked disaccharides such as the galactopyranose dimer 32 [51,52]. 

In addition to the silicon-based in situ activation of hemiacetal donors, there has been a significant body of work that uses electrophilic silicon activation of preformed C-l silyl hemiacetal donors [54—67]. However, this work is outside the scope of this discussion. 

This method has been used only a few times, despite the high yields reported. In the procedure, the hemiacetal was activated with tributylphosphine oxide (4.5 equiv) and triflic anhydride (2.1 equiv) for 2 h at 0 °C, followed by an addition of the giycosyi acceptor. As a result, the isopropyl riboside 46 was prepared in 93% and the cho-lestanyl riboside 47 was prepared in 75%, both with a-anomeric selectivity. 

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