Iodohydrin synthesis

The ready reduction of iodohydrins is utilized in the Cornforth reaction for preparing olefins from epoxides. Here the opening and reduction are carried out in one step by treatment of the epoxide, in an acetic acid-sodium acetate buffer, with sodium iodide and zinc. A less common use of iodohy-drin reduction is illustrated in the synthesis of the diene (127) ... 

One of the few industrial examples of the asymmetric synthesis of halohydrins is in a process to the human immunodeficiency virus (HIV) protease inhibitor, Indinavir.190 The y,8-unsaturated carboxamide 23 is smoothly converted into iodohydrin 24 (92%, 94% de) (Scheme 9.34). (For more on the chemistry of the indanol, see Chapter 24.)191... 

In this reaction sequence, a different fatty acyl group can be substituted at the sn-1 position of the optically active iodohydrin, and then subsequently a different fatty acyl residue can be substituted at the sn-2 position. This derivative is then converted by a series of steps to the desired phosphatidylcholine form. If one s mind is set on a de novo synthesis, then reference should be made to the classic experimental paper by de Haas and van Deenen (1961) (and also earlier publications) and an equally impressive review article on phospholipid synthesis by Eibl (1980). 

Organophosphorus reagents based on triphenylphosphine, or trimethylsilyl iodide, may be used to deoxygenate epoxides to re-form the parent alkene. Reactions based on this, or on a related scheme using the reduction of an iodohydrin, have been used in the synthesis and protection of alkenes as their epoxides (Scheme 2.23). 

A different route to these types of compounds is illustrated by the synthesis of perhydropyrrolo[2,l-Z>][l,3]oxazin-6-one (448). The tetrahy-dropyranyl ether (445), derived from trimethylene iodohydrin, was boiled... 

EUmimtion of iodohydrins. Treatment of the iodolactone (1) in dry pyridine with 1.3 eq. of mesyl chloride at -20° for 2 hr. and at 0° for 1.5 hr. affords the unsaturated lactone (2) in practically quantitative yield. The reaction provided a key step in the synthesis of A prostaglandins, which previously were available from the primary E prostaglandins by dehydration of the )S-kctol unit. 

Elimination of iodohydrias. Treatment of the iodohydrin (1) with freshly distilled phosphoryl chloride in pyridine first at 0° and then at room temperature (30 min.) affords the bicyclic olefin (2) in high yield. The reaction is generally applicable for olefin synthesis,... 

Deoxygenation via iodohydrin intermediates using chlorosilane/sodium iodideand p-toluenesul-fonic acid/sodium iodidehas also been reported. In a natural product synthesis, an epoxide has been deoxygenated with a large excess of triethylsilane at 300 C for 30 h (equation 51). 

During the enantioselective total synthesis of (-)-coriolin, I. Kuwajima and co-workers used a Darzens-type reaction to construct the spiro epoxide moiety on the triquinane skeleton. Interestingly, the usual Darzens condensation where the a-bromoketone was condensed with paraformaldehyde yielded a bromohydrin in which the hydroxymethyl group was introduced from the concave face of the molecule. This bromohydrin upon treatment with DBU gave the undesired stereochemistry at C3 (found in 3-ep/-coriolin). To obtain the correct stereochemistry at C3, the substituents were introduced in a reverse manner. It was also necessary to enhance the reactivity of the enolate with potassium pinacolate by generating a labile potassium enolate in the presence of NIS. The in situ formed iodohydrin, then cyclized to the spiro epoxide having the desired stereochemistry at C3. 

Reduction of iodohydrins. In Cornforth s stereospecific synthesis of a cis or irons olefin, an intermediate is a chlorohydrin of predictable configuration which cannot be reduced directly to the olefin. The conversion is accomplished by three strictly stereospeciflc steps formation of the epoxide, cleavage with HI (Nal—AcOH—EtCOgH), and reduction of the resulting iodohydrin with stannous chloride, phosphoryl chloride, and pyridine. 

Formation of oxacycles via intramolecular radical addition reactions of oxygen-centered radicals under oxidative and reductive conditions is known [116] (see also Chapter 5.2, Volume 2). However, cyclic ether formation via intramolecular displacement reaction of iodohydrins obtained by hydrogen abstraction of oxy radicals has been more widely used, as exemplified in the reports by Suarez [117]. The usefulness of this reaction was amply demonstrated by Paquette in the synthesis of (-t-)-epoxydiclymene (179) [118] (Scheme 61), in which the strained trans-... 

A synthesis of all four stereoisomers [(15,25)-, (1R,2R)-, (15,2/ )- and (l/ ,25)-] of l-amino-2-(hydroxymethyl)cyclobutanecarboxylic acid was presented. The synthesis is based on the chiral glycine equivalent, employed in both enantiomeric forms. The key step involves the cyclization of the silyl-protected iodohydrins to the corresponding sprro derivatives with the aid of the phosphazene base Bu-P4. The final compounds were found to display moderate potency as ligands for the glycine binding of the A-methyl-D-aspartate (NMDA) receptor [43] (Scheme 5.25). 

Additional examples of synthetic application of periodic acid as an oxidant include the oxidative iodination of aromatic compounds [1336-1341], iodohydrin formation by treatment of alkenes with periodic acid and sodium bisulfate [1342], oxidative cleavage of protecting groups (e.g., cyclic acetals, oxathioacetals and dithioacetals) [1315, 1343], conversion of ketone and aldehyde oximes into the corresponding carbonyl compounds [1344], oxidative cleavage of tetrahydrofuran-substituted alcohols to -y-lactones in the presence of catalytic PCC [1345] and direct synthesis of nitriles from alcohols or aldehydes using HsIOe/KI in aqueous ammonia [1346],... 

The argument is closely analogous to that used to explain the regioselectivity of formation of bromoacetoxy compounds (Table 9.2) formed in the addition of bromine to alkenes in acetic acid. Similarly, addition of bromine to alkenes in water produces bromohydrins. Although they are more difficult to synthesize, iodohydrins and fluorohydrins are also known. For a review of the synthesis and reactions of halohydrins, see Rosowsky, A. in Weissberger, A., Ed. Heterocyclic Compounds with Three- and Four-Membered Rings, Part One Wiley-Intersdence New York, 1964 p.l. 

Phosphatidylethanolamine is usually synthesized from phosphatidic acid or from iodohydrin diesters. The analogous route to that of phosphatidylcholine from glycerophosphorylcholine is not usually used because it is difficult to obtain the substrate in a sufficiently pure state. Care must be taken during the synthesis of phosphatidylethanolamine to protect the unsubstituted amino function. 

One simple procedure allows the synthesis of phosphatidylserine by condensation of phosphatidic acid with an amino- and carboxy-protected serine. iV-Carbobenzoxyl-DL-serine benzyl ester was condensed with the phosphatidic acid in the presence of tri-isopropylbenzenesulphonyl chloride. The protecting groups were then removed by hydrogenation which limits the method to saturated phosphatidylserines. However, the use of different protecting groups should allow this method to be used for unsaturated compounds. An alternative procedure involves the introduction of the phosphate and serine functions via a complex silver salt to glycerol iodohydrin diesters (de Haas etal, 1964). 

E)-4-hydroxyenestannanes, with 2 extra C-atoms 44, 850 a-hydroxyketones 43,1 P-hydroxyketones 44,627 hydroxynitriles, synthesis 43, 558 2-hydroxythioethers 43,450 rran5-l,2-iodohydrins 44 922 ketene acetals, cyclic 44, 575... 

The synthesis of the epoxide 48 is described in Scheme 15.15 in three steps, starting with a diastereoselective allylation of the lithium (Z)-enolate of 50 followed by a diastereoselective conversion of 51 to iodohydrin 52 via NIS-mediated cyclic iodoimidate formation and hydrolysis. Finally a base-mediated conversion of 52 to the epoxide 48 was accomplished, with all three steps giving excellent yields [29]. 

Duan and Smith developed a diastereoselective electrophilic cyclization of carbonates derived from homoallylic alcohols 98 via reaction with iodine monobromide to afford a-iodocarbonates 99 (Figure 25.13). These can further be utilized as intermediates for the synthesis of epoxy alcohols, iodohydrins, diols, triols, cyclic carbonates, and so on ... 

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