Hemiacetal synthesis

The reaction starts of with a protonation - use the catalyst. Resist the urge to protonate the 4-hydroxyl, but go for the one at position 1 that has the added functionality of the hemiacetal linkage. It is going to be the more reactive one. Protonation is followed by loss of water as leaving group. The intermediate oxonium cation shown is actually a resonance form of the simpler carbocation now you can see the role of the adjacent oxygen. The reaction is completed by attack of the nucleophile, the 4-hydroxyl of another molecule. This is not special, but is merely another version of the hemiacetal synthesis done in part (a). 

Kluge, M. and Sicker, D. 1996. Double diastereoselective glucosidation of cyclic hemiacetals synthesis of the 1,4-benzoxazinone acetal glucosides GDIBOA and GDIMBOA from Gramineae. Tetrahedron 52, 10389-10398... 

The assignment of the absolute cofiguration was performed by the Mosher method as illustrated below. The sample of the resulting (S,/ )-diastereomer was derivatized to the benzoate by treatment with HA1(/-Bu)2 followed by benzoylation and then compared with the product of the asymmetric hemiacetal synthesis. In this manner the product was shown to be (5). 

The synthesis of 11-oxaprostaglandlns from o-glucose uses the typical reactions of gl cofuranose diacetonide outlined on p. 267. Reduction of the hemiacetal group is achieved a thioacetal. The carbon chains are introduced by Wittig reactions on the aldehyde grou] which are liberated by periodate oxidation and laaone reduction (S. Hanessian, 1979 G Lourens, 1975). 

Structural drawings of carbohydrates of this type are called Haworth formulas, after the British chemist Sir Walter Norman Haworth (St Andrew s University and the University of Birmingham) Early m his career Haworth contributed to the discovery that carbohydrates exist as cyclic hemiacetals rather than m open chain forms Later he col laborated on an efficient synthesis of vitamin C from carbohydrate precursors This was the first chemical synthesis of a vitamin and provided an inexpensive route to its prepa ration on a commercial scale Haworth was a corecipient of the Nobel Prize for chem istry m 1937... 

A variation involves the reaction of benzylamines with glyoxal hemiacetal (168). Cyclization of the intermediate (35) with sulfuric acid produces the same isoquinoline as that obtained from the Schiff base derived from an aromatic aldehyde and aminoacetal. This method has proved especially useful for the synthesis of 1-substituted isoquinolines. 

An alternative approach to the use of a-aminoketones involves acetals (72JOC221) and pyrazine-2,3-diones have been synthesized by this route (Scheme 58). The acetals are readily available from the phthalimido derivatives via the a-chloroketones. Hemiacetals have also served as a starting point for pyrazine synthesis, although in most cases hemiacetals are too labile to be easily prepared examples are common in the 2-amino-2-deoxy sugar series 2-amino-2-deoxy-D-glucose for example dimerizes to the pyrazine (101) when generated in situ from the hydrochloride salt (68JAP6813469). 

Animal cells can modify arachidonic acid and other polyunsaturated fatty acids, in processes often involving cyclization and oxygenation, to produce so-called local hormones that (1) exert their effects at very low concentrations and (2) usually act near their sites of synthesis. These substances include the prostaglandins (PG) (Figure 25.27) as well as thromboxanes (Tx), leukotrienes, and other hydroxyeicosanoic acids. Thromboxanes, discovered in blood platelets (thrombocytes), are cyclic ethers (TxBg is actually a hemiacetal see Figure 25.27) with a hydroxyl group at C-15. 

Heat of combustion, 113 Heat of hydrogenation, 186 table of, 187 Heat of reaction, 154 Helicase, DNA replication and, 1106 Hell-Volhard-Zelinskii reaction, 849 amino acid synthesis and. 1025 mechanism of, 849 Heme, biosynthesis of, 966 structure of, 946 Hemiacetal, 717 Hemiketal, 717 Hemithioacetal, 1148 Henderson-Hasselbalch equation,... 

The sequence was successfully applied to the synthesis of the phthalide isoquinoline hemiacetals (-)-egenine (6) and (-)-corytensine (7) from the bis-oxygenated precursor 513,14. 

Polysubstituted 3-thiofiirans which are receiving a great interest as flavour and odour chemicals have been obtained by mono-//J5osubstitution and ortho-metallation from 3,4-dibromofuran <96T4065>. Dihydrofuran is used in a new synthesis of ketones from acids via acyl hemiacetals (Scheme 8, <96JOC6071>). 

The indium-mediated allylation of trifluoroacetaldehyde hydrate (R = H) or trifluoroacetaldehyde ethyl hemiacetal (R = Et) with an allyl bromide in water yielded a-trifluoromethylated alcohols (Eq. 8.56).135 Lanthanide triflate-promoted indium-mediated allylation of aminoaldehyde in aqueous media generated (i-airiinoalcohols stereoselectively.136 Indium-mediated intramolecular carbocyclization in aqueous media generated fused a-methylene-y-butyrolactones (Eq. 8.57).137 Forsythe and co-workers applied the indium-mediated allylation in the synthesis of an advanced intermediate for azaspiracids (Eq. 8.58).138 Other potentially reactive functionalities such as azide, enone, and ketone did not compete with aldehyde for the reaction with the in situ-generated organo-indium intermediate. 

Vassilikogiannakis and coworkers described a simple sequential process for the biomimetic synthesis of litseaverticillol B (4-159) which includes a cycloaddition of 4-158 and singlet oxygen to give 4-160, followed by ring opening to afford the hydro-genperoxide 4-161 (Scheme 4.34) [55]. Reduction of 4-161 led to the hemiacetal 4-162, which underwent an aldol reaction to afford 4-159. 

Scheme 27 summarizes Yamamoto s synthesis of lardolure (16), the aggregation pheromone of the acarid mite, Lardoglyphus konoi [45]. The key-step was the transformation of acetal A to hemiacetal B. 

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]. 

Synthesis of Oxygen Heterocycles (Excluding Epoxides, Hemiacetals, Lactones and Acetals) as Pheromones... 

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. 

The subsequent deprotection of the hemiacetal concluded the synthesis of 1. We also successfully used this convergent approach to synthesize nakiterpiosinone (2) and 6,20,25-< /E-nakiterpiosiii (49). 

Such a secondary photoreaction can be avoided by trapping the unsaturated aldehyde, e.g. as a hemiacetal. This principle is demonstrated in the synthesis of a furanoid sesquiterpene (2.6)210). 

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... 

An interesting variant involves the use of an allylic alcohol as the alkene component. In this process, re-oxidation of the catalyst is unnecessary since the cyclization occurs with /Uoxygen elimination of the incipient cr-Pd species to effect an SN2 type of ring closure. Both five- and six-membered oxacycles have been prepared in this fashion using enol, hemiacetal, and aliphatic alcohol nucleophiles.439,440 With a chiral allylic alcohol substrate, the initial 7r-complexation may be directed by the hydroxyl group,441 as demonstrated by the diastereoselective cyclization used in the synthesis of (—)-laulimalide (Equation (120)).442 Note that the oxypalladation takes place with syn-selectivity, in analogy with the cyclization of phenol nucleophiles (1vide supra). 

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). 

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