Hydroboration, oxidative

Synthesis of (A) started with the combination of 2,4,6-trimethylphenol and allyl bromide to give the or/Ao-allyl dienone. Acid-catalyzed rearrangement and oxidative hydroboration yielded the dienone with a propanol group in pore-position. Oxidation of the alcohol and bromolactonization (see p. 273) followed. Bromine and the lactone ring were trans in the product as expected (see p. 273). Treatment with aqueous potassium hydroxide gave the epoxy acid, which formed a crystalline salt with (R)-l-(a-naphthyDethylamine. This was recrystallized to constant rotation. 

The structure of (24) was established by the chemical correlation shown in Scheme 3. Reduction of (24) with NaBH4 gave a mixture of (26), O-to-N acyl migration product, and (27) the latter was methylated to (29) which was identical with the product formed from the enamine (28) by oxidative hydroboration. 

This rule has found wide applicability in the field of structure elucidation. For example, in the oxidative hydroboration of (4-)car-2-ene and (- -)car-3-ene, corroborative evidence for the proposed stereochemistry of the respective products (20) and (21) has been obtained from the solvent shifts of the 10-methyl protons (d =<5cdci3 CeHe)-... 

A.2.3. Hydroboration-Oxidation Hydroboration is a stereospecific syn addition. Hydroboration is covered in further detail in Section 5.7. The reaction occurs by an electrophilic attack by borane or alkylborane on the double bond with a concerted shift... 

The highly selective asymmetric addition of organolithiums to acyclic imines and N-aryl group oxidative removal provided a facile and efficient synthetic route to the optically active 1-substituted tetrahydroisoquinoline (TIQ) 81 [74] (Scheme 24), (R)-(-i-)-salsohdine (84) [71] (Scheme 25), and optically pure a-amino acid derivatives 88 bearing a bulky a-substituent [75] (Scheme 26). The reaction of organoiithium reagents with the acyclic imine 78 and subsequent cy-clization of the secondary amine under Moffat oxidation conditions, after oxidative hydroboration of 79, gave 80 (Scheme 24). 

Oxidative hydroboration 91) of lactone 11.49 afforded a mixture of four lactarorufins (Scheme 20), in which diols 11.30 and 11.33, arising from a attack of diborane, largely predominated (more than 90%). The same type of stereoselectivity was observed for other addition reactions, i.e. epoxidation, osmylation, hydrogenation (775), (704), 43) to 2,9, 3,4- or 6,7-double bond of lactaranolides and marasmanes. Apparently, the tricyclic structures of these substrates provided enough conformational and steric bias to direct approach of reagents from the same side as the bridgehead protons H-2 and H-9. However, when the double bond was located in a different position, exceptions were observed 98). 

Hydroboration-oxidation, hydroboration-C2-homologation, reduction byLiAlH4 and acetylation of alcohols by AcCl/Py procedures were described by us in detail [1]. Epoxydation of 15 into 16 was described in [40]. 

The hydration of alkenes with aqeuous add (Table 6.1, entry 2 Scheme 6.23) or, more conveniently in the laboratory, by oxymercuration (Table 6.1, entry 6) and reduction (Scheme 6.24), can be usefully compared with oxidative hydroboration (Table 6.1, entry 17 Scheme 6.25) as alternative synthetic techniques for preparation of alcohols. 

Scheme 6.25. A representation of the oxidative hydroboration of 1-methylcyclopentene (as a typical alkene). The addition of boron and hydride (H ) is suprafacial with the double bond attacking the boron so as to build up charge on that carbon of the double bond that would be the most stable carbocation it is to this carbon of the double bond that the hydride (H") adds. In the oxidation step, the anion of hydrogen peroxide (H02 ) attacks the boron. Subsequent rearrangement of carbon to oxygen with oxygen-oxygen bond cleavage produces the alcohol. Only one ligand to boron is shown to emphasize the oxidation process.

Further, it should be clear that if a chiral alkene such as the terpene a-pinene (Scheme 6.27) is used, and if steric effects are important, then the specificity of addition would result in a chiral borane reagent. Use of the chiral borane reagent, in, for example, oxidative hydroboration, would then produce a chiral alcohol. 

Finally, because the adduct of borane with an alkene is formed reversibly, when the temperature is raised, borane is lost and the least sterically hindered alkene results. As shown in Scheme 6.28, the initially formed adduct, at temperatures above ca. >150°C, produces (reversibly) an alkene, isomeric with the original. The readdition and ehmination reoccurs until the double bond has migrated to the terminus. Three possibilities then intrude, viz (a) borane is removed and the isomeric alkene is isolated (b) oxidative hydroboration is effected to produce a primary alchol or (c) reduction can be produced by addition of a carboxylic acid. ... 

As was the case for alkenes, other reactions in which an oxidation will be seen to have occurred (e.g., oxidative hydroboration) are also found for alkynes. Following the same pattern, however, dictates that those reactions be found under the general heading of Addition (vide infra). 

A synthetic method used to accomplish this is an indirect one known as hydroboration-oxidation. Hydroboration is a reaction in which a boron hydride, a compound of the type R2BH, adds to a carbon-carbon tt bond. A carbon-hydrogen bond and a carbon-boron bond result. 

Chiral boranes are easily available from the chiral pool of Nature, specifically from terpenes and sesquiterpenes, as indicated by the retrosynthetic arrow in the Fig. 6.3. They enable enantioselective hydroboration of alkenes in which a stereo-genic centre is generated on addition of an hydride ion. This important synthetic aspect of oxidative hydroboration, however, is beyond the scope of this chapter. 

The hydroxyalkyl compounds of the type 120 (where R = GH2(GH2) GH20H and / = 2,3,4, or 6) have been prepared as well as the Gp analogs by the oxidative hydroboration of the 77 -alkenyl compounds Gp""Fe(GO)2 (GH2) GH=GH2 (where Gp = Gp or Gp and n = 2,3,4, or 6). These new cu-hydroxy-alkyl compounds were isolated as low-melting yellow solids or yellow-brown oils and characterized by IR, NMR, and mass spectrometry. 

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