Alcohols through hydroboration-oxidation

Alcohols from Alkenes Through Hydroboration-Oxidation... 

ALCOHOLS FROM ALKENES THROUGH HYDROBORATION-OXIDATION ANTI-MARKOVNIKOV SYN HYDRATION... 

Alcohols from Alkenes through Hydroboration-Oxidation Anti-Markovnikov Syn Hydration... 

Although this three-step synthesis is the most efficient answer, a related approach derives from our earlier consideration of ketone synthesis with the use of an alcohol. It, too, proceeds through an alkyne. Construction of bond a of the target molecule, shown earlier, requires addition of an organo-metallic reagent to a six-carbon aldehyde, which, in turn, may be produced through hydroboration-oxidation (Section 13-8) of the terminal alkyne shown in the preceding scheme. 

A solution of CuCl (1.5 mg, 15 pmol), the NHC ligand precursor (8.7 mg, 17 pmol), and NaOMe (32.4 mg, 0.600 mmol) in THF (0.40 mL) was stirred for 15 min at RT. The organoboronic acid neopentylglycol ester (0.600 mmol) was added and the mixture stirred for 5 min at RT. The allylic phosphate (0.300 mmol) was then added with additional THF (0.20 mL), and the resulting mixture was stirred for 16 h at 30 °C. After dilution wifli EtOAc, the mixture was passed through a pad of silica gel with EtOAc, and the solvent was then removed under vacuiun. The residue was purified by silica gel preparative TLC using EtOAc/hexane to afford the desired product. For ee analysis, the product was converted into the corresponding primary alcohol via a hydroboration-oxidation sequence. 

As a consequence, hydroboration-oxidation gives us a method for the preparation of alcohols that cannot normally be obtained through the acid-catalyzed hydration of alkenes or by oxymercuration—demercuration. 

In a synthesis of heteroyohimbane alkaloids tetrahydroalstonine 362 and akuammigine 363, Uskokovic prepared a chemoenzymatic process alcohol 364 [85, 86]. This compound afforded ester 366 with R configuration at C-15 after orthoester rearrangement through a chair-Hke transition state 365. Functionahza-tion at C-16 followed by a stereoselective hydroboration-oxidation afforded compound 367 with the DE rings framework of the alkaloids (Scheme 6.61). The same rearrangement has been used by Bosch in a synthesis of alkaloid tubifoHne 368 [87] (Scheme 6.61). 

Scheme 27 Synthesis of y-alkyl-substituted alcohols through Cu-catalysed asymmetric allylic alkylation of allyl bromides with organolithium reagents followed by a hydroboration/oxidation...

An extensive array of chiral phosphine ligands has been tested for the asymmetric rhodium-catalyzed hydroboration of aryl-substituted alkenes. It is well known that cationic Rh complexes bearing chelating phosphine ligands (e.g., dppf) result in Markovnikoff addition of HBcat to vinylarenes to afford branched boryl compounds. These can then be oxidized through to the corresponding chiral alcohol (11) (Equation (5)) ... 

Zinc-mediated Barbier-t) e addition of 238, followed by Luche s procedure obtained a mixture of the homoallylic alcohol diastereomers 239 and 240. Alcohol 239 was carried through benzoylation, deketalization, silylation, and ozonolysis, to produce C-branched y-lactone 241. Benzoylation of 240 followed by hydroboration, PCC oxidation, debenzoylation, and alkaline-promoted cyclization directly formed C3-branching 2-deoxyfuranose 242 [87] (O Scheme 63). A novel method for stereoselective synthesis of 4 -a-carbon-substituted nucleosides, through epoxidation of 4, 5 -unsaturated nucleosides and SnCU-promoted epoxy ring opening, was... 

Hydroboration of alkenes yields alkylboranes, and these, we have seen (Sec. 15.9), can be converted through oxidation into alcohols. But oxidation is only one of many reactions undergone by alkylboranes. Since the discovery of hydroboration in 1957, H. C. Brown and his co-workers (p. 507) have shown that alkylboranes are perhaps the most versatile class of organic reagents known. 

Hydroboration occurs by a concerted process and takes place through a four-membered cyclic transition state, formed by addition of a polarized B—H bond (boron is the more positive) to the alkene double bond (5.2). This is supported by the fact that the reaction is stereospecific, with syn addition of the boron and hydrogen atoms. The reaction can also be stereoselective, with hydroboration taking place preferentially on the less hindered side of the double bond. Stereospecific addition of borane to a 1-alkylcycloalkene such as 1-methylcyclohexene, gives, after oxidation of the organoborane product (see Scheme 5.21), almost exclusively the trans alcohol product (5.3). 

Ring expansion with Tamura et al. s Beckmann reagent, followed by dechlorination with Zn-Cu couple in methanol saturated with ammonium chloride, provided key pyrrolidinone intermediate 197 in 72% overall yield from 193. The intermediate 197 was then converted by using selenium dioxide and tcrt-butyl hydroperoxide into allylic alcohol (62%), which yielded the desired 1,3-diol 198 through rhodium-catalyzed hydroboration and oxidation as a 1 1 mixture of diastereomers in 72% yield. A seven-step reaction sequence then converted the diol 198 into (-l-)-retronecine 199, which was indistinguishable from an authentic sample of the natural product obtained by hydrolysis of natural monocrotaline (Scheme 16.29). ... 

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