Hydroboration and oxidation

The (partial) description of the synthesis and coupling of the five fragments starts with the cyclohexyl moiety C —C. The first step involved the enantio- and diastereoselective harpless epoxidation of l,4-pentadien-3-ol described on p. 126f. The epoxide was converted in four steps to a d-vinyl d-lactone which gave a 3-cyclohexenecarboxylate via Ireland-CIaisen rearrangement (cf. p. 87). Uncatalysed hydroboration and oxidation (cf. p. 131) yielded the desired trans-2-methoxycyclohexanol which was protected as a silyl ether. The methyl car-... 

It IS customary to combine the two stages hydroboration and oxidation m a sm gle equation with the operations numbered sequentially above and below the arrow... 

The combination of hydroboration and oxidation leads to the overall hydration of an alkene. Notice, however, that water is not a reactant. The hydrogen that becomes bonded to carbon comes from the organoborane, and the hydroxyl group from hydrogen peroxide. 

Quebrachitol was converted into iL-c/j/roinositol (105). Exhaustive O-isopropylidenation of 105 with 2,2-dimethoxypropane, selective removal of the 3,4-0-protective group, and preferential 3-0-benzylation gave compound 106. Oxidation of 106 with dimethyl sulfoxide-oxalyl chloride provided the inosose 107. Wittig reaction of 107 with methyl(triphenyl)phos-phonium bromide and butyllithium, and subsequent hydroboration and oxidation furnished compound 108. A series of reactions, namely, protection of the primary hydroxyl group, 0-debenzylation, formation of A-methyl dithiocarbonate, deoxygenation with tributyltin hydride, and removal of the protective groups, converted 108 into 7. 

Synthesis of PIB prepolymers. fm-Chlorine-telechelic PIB (Mn=4,000 MVf/Mn 1.09) (7), and an allyl-telechelic PIB (Mn=9,500 Mw/Mn 1.14) (7,8) were prepared by living carbocationic polymerizations. The tert-chlorine ended PIB was quantitatively dehydrochlorinated (9) to -C(CH3)=CH2 terminated polymer. Both olefin-telechelic PIBs were then hydroborated and oxidized (10) to prepare the primary hydroxyl termini. The hydroxyl-telechelic polymers were esterified with methacryloyl chloride to methacrylate-telechelic PIBs, MA-PIB-MA (11). 

Hydroboration and oxidation of 160 yields an alcohol that is subsequently oxidized with PDC to give ketone compound 161. Enolization and triflation converts this compound to enol triflate 162, which can be further converted to x,/i-unsaturated ester 163 upon palladium-mediated carbonylation methox-ylation. The desired alcohol 164 can then be readily prepared from 163 via DIBAL reduction. Scheme 7 50 shows these conversions. 

The reactivity of 464 was also used to prepare perhydrofuropyrans with the same methodology as shown in Scheme 129, but with an epoxide as second electrophile. Diols 467 were obtained in 35-68% yield which, after hydroboration and oxidation reactions (as shown in Scheme 128), gave perhydrofuropyrans 468 in 57-64% yield. This heterocyclic unit is present in many natural products, azadirachtins being probably the most important ones. ... 

The acid portion of 1 was assembled by enantio-and diastereocontrolled addition of Z-crotyl borane to the aldehyde 8, following the Brown protocol. Hydroboration and oxidation led to 9, which was condensed with the allenyl silane 10 to give 11 with high diastereocontrol. Conversion of the alcohol to the iodide followed by three-carbon homologation by the Myers procedure then led to 1, which was cyclized with > 10 1 regio- and diasterocontrol to give 12. Ozonolysis and methylenation of the less hindered ketone then delivered 3. 

This type of disconnection is mainly used for the preparation of dipeptides of type Xaai >[ , CH=CH]Gly. It allows control of the stereochemistry of the Xaa residue by starting from chiral a-amino aldehydes. For the construction of the /ram -p,y-unsaturated carboxylic acid moiety, the use of the triphenylphosphonium salt 31 (Scheme 9) derived from 3-chloro-propanoic acid was not suitable.14 Instead, the trimethylsilylprop-2-ynyl phosphonium salt 33 serves as a three-carbon unit, which can be converted into the P,y-unsaturated acid by hydroboration and oxidation. The required Boc-protected a-amino aldehyde 32 can be prepared using virtually racemization-free procedures. 37 However, at the end of the reaction sequence, racemization has been detected, especially for Boc-Phet )[ , CH=CH]Gly-OH, but not for the Ala and Pro analogues. 63 A mixture of E- and Z-enynes 34 and 35 is formed (8 2 to 9 1), which can be separated by column chromatography. 4,48 50 53 64 65 ... 

Hydroboration and oxidation of 3,4-dihydro-2-methoxy-2//-pyran gives a mixture of cis- and rra s-5-hydroxy-2-methoxytetrahydropyran (70CJC2334). After methylation, trans-2,5-dimethoxytetrahydropyran was isolated in small amounts. The cis isomer was obtained from 3,4-dihydro-3-methoxy-2//-pyran via 3-bromo-2,5-dimethoxytetrahydropyran. 

Three isomers of the substituted cyclobutanes 33, 34 and 35 are obtained by the [2+2] cycloaddition of isoprene, and separated at low temperature from other cooligomers without undergoing Cope rearrangement. When the mixture was subjected to hydroboration and oxidation, the alcohol 37 was obtained from the isomer 34, and easily separated from 35 and the diol 36. The alcohol 37 is a pheromone called grandisol [11]. Although overall yield was 15%, this is the shortest synthetic route to this pheromone. 

Aqueous chromic acid has been used to oxidize alkylboranes derived from cyclic alkenes to ketones. For example, hydroboration and oxidation of 1-methylcyclohexene converts it into 2-methylcyclohexanone (Equation B2.10). 

The oxidation of primary and secondary trialkylboranes with pyridinium chlorochromate (PGG) provided aldehydes or ketones.504-507 An oxidative conversion of alkenes into a carbonyl compound was conducted by tandem hydroboration and oxidation with excess A-methylmorpholine-A-oxide (NMO) in the presence of Pr4NRu04 (TPAP) (Equation (105)).508... 

For the first example, we chose to acylate olefin alcohol la. This was readily accomplished using acetic anhydride and 4-DMAP in pyridine to provide ester 17. Methylenation, using Takai s (10) protocol, yielded the acyclic enol ether 18 which was subsequently cyclized with 15 mol % of the Schrock catalyst 6 in hot toluene to afford the glycal 19 in good yield. Hydroboration and oxidative work-up led to the methyl-C-glycoside 20 (Scheme 4). With this proof of principle in hand, we then set out to prepare a number of additional examples as shown in Table 1 (11). 

Problem 15.13 Synthesize (a) p-methoxybenzaldehyde from benzene (b) cyclohexylethanal by hydroboration and oxidation (c) phenylacetaldehyde, using 1,3-dithiane (d) phenyl n-propyl ketone from a dithiane (e) cyclohexyl phenyl ketone from PhCOOH and RLi (/) 2-heptanone, using a cuprate. ... 

Somewhat less direct procedures have also been recognized. In 1967, Corey and Glass described the preparation of hydrocarbon 138 and its conversion through hydroboration and oxidation to ketone 139 (Scheme 23).216 Subsequent Baeyer-... 

Acylsilanes may serve as synthetic equivalents of cai boxylic acids when treated with alkaline hydrogen peroxide. Especially attractive is the one-pot conversion of the ethynyl group of 1-alkynes into monosubstituted acetic acids via sequential silylation, hydroboration, and oxidation, as depicted below. 

The known bicyclo[3.1. Ojhexene 167 was hydroborated and oxidized to afford anti alcohol 168 in up to 80% yield. Chromic acid oxidation of 168 was followed by p elimination of malonate anion with EtaN to produce enone 169 (86%). Initial deprotonation of 169 followed by the addition of cuprate 166 afforded an 82% yield of 170. As expected, Michael addition to the enone occurred anti to the malonate unit. Reduction of ketone 170 with LiBH4 gave a 4 1 mixture of Cy alcohols, the major product being the desired a-hydroxy isomer. Chromatographic separation of the alcohols, followed by protection and ester cleavage, then gave the diacid 171. 

A simple example is the oxidation of an alkene to a carboxylic acid 93 in Evans synthesis of cytovaricin. The alkene had been put in by allylation and the optically active unsaturated alcohol 90 was first protected 91 and then subjected to hydroboration and oxidation. Protection before the second alcohol appeared prevented impossible chemoselectivity problems.14... 

The hydroboration of alkynes using borane (BH3) produces an intermediate vinylic borane, which then reacts with BH3 in a second hydroboration the two boron groups add to the less hindered end of the triple bond. However, when a bulky dialkylborane (HBR2) is used, steric hindrance prevents a second hydroboration, and oxidation of the intermediate vinylic borane produces an enol, which tautomerises to an aldehyde. (For a related mechanism, see Section 6.2.2.5.)... 

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