Hydroboration alcohol synthesis

We ve already looked at several alcohol synthesis reactions hydration of an alkene, oxymeixruration/demeicu ration, hydroboration, and nucleophilic substitution. 

Because the oxidation step in the hydroboration-oxidation synthesis of alcohols takes place with retention of configuration, the hydroxyl group replaces the boron atom where it stands in the alkylboron compound. The net result of the two steps (hydroboration and oxidation) is the syn addition of —H and —OH. We can review the anti-Markovnikov and syn aspects of hydroboration-oxidation by considering the hydration of 1-methylcyclopentene, as shown in Fig. 8.3. 

Hydroboration was discovered by Professor Herbert C. Brown (1912-2004). This reaction is so useful in synthesis that Brown s work earned him a Nobel Prize in 1979. We will describe here only one practical example of hydroboration, a two-step alcohol synthesis from alkenes. 

Our previous method for alcohol synthesis, hydration of aikenes, necessarily produced the more substituted alcohol. So now we have complementary synthetic methods for producing hoth possible alcohols from a given alkene (Fig. 9.69). Direct hydration gives the more substituted product (Markovnikov addition) and the indirect hydroboration/oxidation method gives the less substituted alcohol (anti-Markovnikov addition). Be sure to add these reactions to your file-card collection of synthetically useful reactions. 

A Stereospeeific and Regioselective Alcohol Synthesis hy Hydroboration-Oxidation... 

Hydroboration - regloseiective and stereoselective (syn) addition of BH3 (RBH2, R2BH) to olefins. Synthesis of alcohol including optically active alcohols from olefins. Also useful In synthesis of ketones by stitching ot olefins and CO... 

Because the olefin geometry in compound 9 will most certainly have a bearing on the stereochemical outcome of the hydroboration step, a reliable process for the construction of the trans trisubsti-tuted olefin in 9 must be identified. A priori, the powerful and predictable Wittig reaction28 could be used to construct E u, [3-unsaturated ester 10 from aldehyde 11. Reduction of the ethoxycarbonyl grouping in 10, followed by benzylation of the resulting primary alcohol, would then complete the synthesis of 9. Aldehyde 11 is a known substance that can be prepared from 2-furylacetonitrile (12). 

An important stage in the synthesis has been reached. The reaction processes described thus far have proceeded uneventfully and have culminated in the synthesis of compound 9. The stage is now set for an evaluation of the first of two hydroboration reactions. Treatment of 9 with diborane in THF, followed by standard alkaline hydrogen peroxide workup, furnishes an 8 1 stereoisomeric mixture of alcohols in favor of 28 (85 % total yield). On the basis of some important precedent,32 it is presumed that compound 9 preferen-... 

The conversion of a thiolactone to a cyclic ether can also be used as a key step in the synthesis of functionalized, stereochemically complex oxacycles (see 64—>66, Scheme 13). Nucleophilic addition of the indicated higher order cuprate reagent to the C-S double bond in thiolactone 64 furnishes a tetrahedral thiolate ion which undergoes smooth conversion to didehydrooxepane 65 upon treatment with 1,4-diiodobutane and the non-nucleophilic base 1,2,2,6,6-pentamethylpiperidine (pempidine).27 Regio- and diastereoselective hydroboration of 65 then gives alcohol 66 in 89 % yield after oxidative workup. Versatile vinylstannanes can also be accessed from thiolactones.28 For example, treatment of bis(thiolactone) 67 with... 

A biomimetic synthesis of benzo[c]phenanthridine alkaloids from a protoberberine via the equivalent of a hypothetical aldehyde enamine intermediate has been developed (130,131). The enamide 230 derived from berberine (15) was subjected to hydroboration-oxidation to give alcohol 231, oxidation of which with pyridinium chlorochromate afforded directly oxyche-lerythrine (232) instead of the expected aldehyde enamide 233. However, the formation of oxychelerythrine can be rationalized in terms of the intermediacy of 233 as shown in Scheme 41. An alternative and more efficient... 

In the synthesis of methyl corydalate (55) Nonaka et al. (65) used the methiodide of (-t-)-tetrahydrocorysamine (65) as substrate and the Hofmann degradation method for ring opening (Scheme 16). The methine base (66) on hydroboration afforded alcohol 67, identical with a product obtained from 55 by lithium aluminium hydride reduction. 

This is likely due to four groups on the ring being in the axial position. We were successful by protecting the alcohol as the mesylate, but further reactions did not prove fruitful in moving forward in the total synthesis. These reactions, as well as optimization of the hydroboration described, are discussed in detail in [48]. 

One of royal jelly acids (10-hydroxy-2-decenoic acid) (141) was prepared from the telomer of acetoacetate, 142 (128). The terminal double bond was converted to terminal alcohol by hydroboration. The internal double bond was reduced and then reintroduced at the conjugated position by the addition of phenylselenyl group, and its oxidative removal completed the synthesis ... 

Ligand 73 was prepared directly from a single enantiomer of the corresponding naphthol of QUINAP 60, an early intermediate in the original synthesis, and both enantiomers of BINOL. Application in hydroboration found that, in practice, only one of the cationic rhodium complexes of the diastereomeric pair proved effective, (aA, A)-73. While (aA, A)-73 gave 68% ee for the hydroboration of styrene (70% yield), the diastereomer (aA, R)-73 afforded the product alcohol after oxidation with an attenuated 2% ee (55% yield) and the same trend was apparent in the hydroboration of electron-poor vinylarenes. Indeed, even with (aA, A)-73, the asymmetries induced were very modest (31-51% ee). The hydroboration pre-catalyst was examined in the presence of catecholborane 1 at low temperatures and binuclear reactive intermediates were identified. However, when similar experiments were conducted with QUINAP 60, no intermediates of the same structural type were found.100... 

In 1993, Hayashi and co-workers reported a catalytic asymmetric synthesis of alle-nylboranes 256 by palladium-catalyzed hydroboration of conjugated enynes 253 (Scheme 4.66) [105]. Reaction of but-l-en-3-ynes 253 with catecholborane 254 in the presence of a catalyst, prepared from Pd2(dba)3 CHC13 (1 mol%) and a chiral mono-dentate phosphine ligand (S)-MeO-MOP 255 (1 mol%), gave an allenylborane 256. The ee of 256 was determined by the reaction with benzaldehyde affording the corresponding optically active homopropargyl alcohols 257 with up to 61% ee (syn anti= 1 1—3 1). 

The iodoetherification strategy was applied to the synthesis of the smaller fragment coupling component 109 as well (Scheme 16). Silylation of alcohol 104 [30] (76% de) allowed the separation of the pure desired diastereomer, which in turn was subjected to hydroboration/oxidation, sulfide formation with thiol 105, and oxidation to give sulfone 106. The requisite y-triethylsilyloxy alkene functionality in 107 was constructed as a diastereomeric E) Z)=l.2 l mixture by another sulfone-based olefination of aldehyde 90 with 106. Treatment of 106 with... 

This is attributed to the unfavourable steric interactions which arise in the transition state that is required for antiperiplanar migration of the exocyclic substituent.143 Some examples of synthesis of alcohols by hydroboration-oxidation are included in Scheme 4.8. More vigorous oxidizing agents such as Cr(VT) reagents effect replacement of boron... 

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