Bromohydrins, synthesis

SCHEME 42.9. Enantioselective bromohydrin synthesis leading to (+)-pericosine A 26. 

Murai, A., Abiko, A., Kato, K., and Masamune, T. (1981) Cationic cyclization of geranonitrile related compoimds via their bromohydrins synthesis of snyderols. Chem. Lett., 10,1125-1128. 

In 1975, van der Baan and Bickelhaupt reported the synthesis of imide 37 from pyridone 34 as an approach to the hetisine alkaloids, using an intramolecular alkylation as the key step (Scheme 1.3) [23]. Beginning with pyridone 34, alkylation with sodium hydride/allyl bromide followed by a thermal [3,3] Claisen rearrangement gave alkene 35. Next, formation of the bromohydrin with A -bi omosuccinimide and subsequent protection of the resulting alcohol as the tetrahydropyranyl (THP) ether produced bromide 36, which was then cyclized in an intramolecular fashion to give tricylic 37. 

The synthesis of other biologically active thiazoles was described by Ohsumi et al. [50] and is shown in Scheme 16. Condensation of phosphonium bromide and 4-methoxy-3-nitrobenzaldehyde gave a 1 1 mixture of (Z)- and (-E)-stilbenes. ( )-stilbene 64 was purified by crystallization and then converted to bromohydrin 65 by NBS-H2O. Oxidation of the bromohydrin by DMSO-TFAA gave the bromoketone intermediate 66, which was condensed with thiocarbamoyl compounds in the presence of Na2C03 in DMF to give the corresponding 2-substituted thiazole derivatives (67a and b). Compound 67a... 

A new elegant stereoselective synthesis of humulene (192) has been achieved by a route (Scheme 22) in which the 11-membered-ring framework [cf. (191)] is produced by cyclization of the 11-allylpalladium complex derived from intermediate (190). Buddledin-A (193), -B (194), and -C (195) are new piscicidal sesquiterpenoids which have recently been isolated from the root bark of Buddleja davidiC The caryophyliane framework of these compounds has been established by spectroscopic data and X-ray analysis of the mono-bromohydrin (196) derived from buddledin A (193). An extension of previous studies on the cyclization of the epoxy-ketone (197) derived from caryophyllene has shown that the base-catalysed cyclization of the isomeric epoxy-ketones (198) and (199) provides compounds... 

The indirect electrochemical generation of propylene oxide via propylene chloro- or bromohydrin using anodically generated hypochlorite or hypobromite has been studied very intensively. The reason is the lack of a technically useful process for the synthesis of propylene oxide by way of heterogeneous catalysis. The propylene halohydrins are saponified using the cathodically generated sodium hydroxide (Eqs. (42)-(47)) (Table 4. No. 12-15)... 

Mildly basic to neutral conditions for the ring closure of 1,3-halohydrins include tetra-phenylantimony methoxide as an effective non-basic reagent for oxetane synthesis from 1,3-bromohydrins (90S106). The salts of (3-halo acids cyclize in ionizing media to oxetan-2-ones, as do (3-diazonium carboxylates (64HC(l9-2)787). Thietanes are obtained analogously. 

Elwesine. The starting material for a synthesis [83] of elwesine (320) [84] (Scheme 48), the 0-protected cyclohexene derivative 321, itself obtained from 4-benzyloxycyclo-hexanone, was converted into a 1 4 diastereomeric mixture of bromohydrins 322 and 323 with N-bromosuccinimide and thence by dehydration to a mixture of a-allyl bromide 324 and the p isomer325. 

Pretazetiine. Ishibashi s formal synthesis [96] of the alkaloid 369 [97] (Scheme 54) in the racemic form commenced with 4-methoxy-l-(3 ,4 -methylenedioxyphenyl)-cyclohex-l-ene (370), which was converted into a mixture of P-bromohydrin 371 and the a-isomer 372. 

The partial synthesis from solasodine of nitrogen-containing analogues of ecdysone has been explored.22 In the successful route, 7V,0-diacetylsolasodine (16b) was treated with TV-bromo acetamide and HCI04. The bromohydrin (26a) that was formed was reductively debrominated with chromous acetate and butanethiol to... 

The products of bromination in water are called bromohydrins. They can be treated with base, which deprotonates the alcohol. A rapid intramolecular Sjyj2 reaction follows bromide is expelled as a leaving group and an epoxide is formed. This can be a useful alternative synthesis of epoxides avoiding peroxy-acids. 

Most of the published syntheses of XIV have been previously summarized (2). One of the more practical large-scale syntheses of XIV in high purity is the one outlined in Figures 3 and 4, which is based on an earlier synthesis by Jacobson and co-workers (41 see also 20b). Thus the diol is converted to the bromohydrin VI by reaction with aqueous HBr in a two-phase system. The crude product is purified by conversion of the alcohol group to a non-volatile borate ester with triethyl borate and removal of the 1,8-dibromooctane by distillation. After hydrolysis of the borate any residual diol is removed by extraction with water. 

The bromohydrin is then quantitatively converted to the THP ether, which is added to LiC=CH-ethylenediamine complex in dimethyl sulfoxide to give VII in very high yield. No purification is required in either of these steps. A shorter synthesis of 9-decyn-l-ol (IX) was subsequently developed. An acetylene "zipper" isomerization (42) with sodio-1,3-diaminopropane is used to convert either 3-decyn-l-ol (VIII) or 2-decyn-l-ol into the terminal alkynol IX. Both of these starting alkynols are commercially available and the saving in labor is advantageous for moderate scale production. 

The synthesis of 6a-methyldigitoxigenin acetate (394) has been reported according to Scheme 19.198 Pregn-4-en-21-ol-3,20-dione was converted into its 6a-methyl derivative (387) using a previously described five-step reaction sequence biological hydroxylation furnished the 14a,12-diol (388) and reduction of the derived 21-acetate gave the 5/3-dihydro-steroid (389). Dehydration furnished the A14-olefin (390) which was converted into the 21-mesylate and thence into the lactone (391) by reaction with the monoethyl ester of malonic acid. The crude lactone was decarbox-ylated, reduced to the 3/3-alcohol (392), and converted into the bromohydrin (393) via its 3/3-acetate and thence by debromination into 6a-methyldigitoxigen 3-acetate... 

The conversion of a diol or bromohydrin to the corresponding epoxide is a well-known and useful method. Recently two methods have been reported that significantly add to this chemistry. A synthesis of a key component of the natural product neocarzinostatin has been reported <07OL45>. In this work, an allenyl zinc bromide was added to a propargylic ketone to provide a chlorohydrin stereoselectively. Treatment of the chlorohydrin with base provided the epoxide. 

Direct synthesis of a-bromo ketones from alkenes is carried out by use of sodium bromite (NaBr02). The reaction proceeds via the bromohydrin (48) as intermediate (equation 19). 

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