Selective reductive bromination

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. 

Syntheses of the 1,2- and the 3,4-dihydrodiols of MBA via Methods II and IV have been described (74). The 1,2- and 3,4-diol dibenzoates of 1,2,3,4-tetrahydro-MBA prepared from MBA via the Li/-NH reduction route were readily separable by crystallization. Introduction of the olefinic bond into the 1,2-position of the 3,4-diol dibenzoate by the usual bromination-dehydrobromination procedure was complicated by the greater facility of bromination by NBS on the methyl group than the 1-position. This problem was solved (Figure 14) by allowing bromination to proceed to the dibromo stage, followed by selective reduction of the bromomethyl group with NaBH in diglyme. The monobromo derivative underwent dehydrobromination... 

By carefully monitoring the pH of the reaction, regioselective diiodination was achieved. Treating imidazole with iodine at pH 12 furnished 2,5-diiodoimidazole. Selective reductive deiodination secured 2-iodoimidazole, which upon bromination afforded 4,5-dibromo-2-iodoimidazole [6],... 

Brief treatment of 2,6-dibromo-2,6-dideoxy-D-mannono- (2) or -D-glucono-lactone (9) (Scheme 3) with potassium fluoride or potassium carbonate in acetone gave the 6-bromo-2,3-monoepoxymannonolactone (10), whereas after a more prolonged reaction time the diepoxylactone 11 was formed [19]. This selectivity reflects the difference in reactivity of the two bromine atoms, as also discussed for the selective reductions above. An interesting observation was that... 

In general, aromatic halogenation proceeds to give the para product. Jallal M. Gnaim of the The Triangle Regional R D Center, Kfar-Qari, Israel, has developed (Tetrahedron Lett. 2004,45, 8471) a procedure that selectively converts phenols such as 1 into the ortho chlorinated product 2. Meta substitution is even more elusive. William R. Roush, now at Scripps Florida, prepared (J. Org. Chem. 2004,69,4906) the valuable meta brominated phenol 4 by perbromination followed by selective reduction. 

The presence of bromine at C-12 does not affect the selectivity 12a-bromo-3a-hydroxy-5/J-pregnane-ll,20-dione is reduced to the 20/ -alcohol by NaBH4 in either aqueous tetrahydrofuran or 2-propanol.72 Similarly, a 17-bromo substituent has no effect.239 LiBH4 has also been used for selective reductions of a 20-ketone in the presence of an 11-ketone.92... 

Another approach in the study of the mechanism and synthetic applications of bromination of alkenes and alkynes involves the use of crystalline bromine-amine complexes such as pyridine hydrobromide perbromide (PyHBts), pyridine dibromide (PyBn), and tetrabutylammonium tribromide (BiMNBn) which show stereochemical differences and improved selectivities for addition to alkenes and alkynes compared to Bn itself.81 The improved selectivity of bromination by PyHBn forms the basis for a synthetically useful procedure for selective monoprotection of the higher alkylated double bond in dienes by bromination (Scheme 42).80 The less-alkylated double bonds in dienes can be selectively monoprotected by tetrabromination followed by monodeprotection at the higher alkylated double bond by controlled-potential electrolysis (the reduction potential of vicinal dibromides is shifted to more anodic values with increasing alkylation Scheme 42).80 The question of which diastereotopic face in chiral allylic alcohols reacts with bromine has been probed by Midland and Halterman as part of a stereoselective synthesis of bromo epoxides (Scheme 43).82... 

Bromothiophene can be prepared by selective reduction of the a-bromine atoms of 2,3,5-tribromothiophene." At the end of the reaction the organic material distills with the water. 

Treating imidazole with bromine in a NaOH solution afforded the complete ring bromination product, 2,4,5-tribromoimidazole. 4-Bromoimidazole was then produced in 62% yield upon selective reductive debromination [5]. The same procedure converted 2-methylimidazole and 1-methylimidazole to 4(5)-iodo-2-methylimidazole [6] and 4(5)-bromo-l-methylimidazole [7], respectively. 

Tribromination of thiophene goes smoothly in 48% hydrobromic acid solution. Since it has long been known that treatment of polyhalogeno-thiophenes with zinc and acid brings about selective removal of a-halogen, this componnd can be nsed to access 3-bromothiophene just as 3,4-dibromothiophene can be obtained by rednction of the tetrabromide. One interpretation of the selective reductive removal is that it involves, hrst, electron transfer to the bromine, then transient anions , thns halogen can be selectively removed from that position where snch an anion is best stabilised - normally an a-position (17.4.1). 

Meerwein-Ponndorf reduction of the ketone obtained by deprotection of compound (191) gave the desired 3P-axial hydroxy product. Selective reduction of the y-lactone ring of this substance was achieved by LiAlH4 in THF at — 30°C to give hemiacetal (192). Subsequent acetalization at C-6, acetylation at C-3, bromination at allylic C-17, and epoxidation converted (192) to (193), which on treatment with zinc dust in ethanol at reflux gave the A -allylic 15 3-ol. Oxidation of the latter, deacetylation, and hydrolysis produced the desired enmein (62). Thus, a relay total synthesis of enmein was achieved (see Scheme 38). 

Selective reduction of benzylidene acetals to form mono-benzyl protected diols was discussed in section 2.3.1, Benzyl ethers but differentiation of the oxygen atoms within benzylidene derivatives can also be achieved in the widely used Hanessian procedure. In this process, benzylic bromination, oxonium ion formation, and nucleophilic attack by bromide ion at the (1°-) 6-position leads to the 4-O-benzoyl-6-deoxy-6-bromo derivative. Figure 2.62 [83]. 

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