Hydroboration-oxidation alcohol synthesis

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... 

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... 

Pearson and Lin (52) developed an elegant approach to the synthesis of optically active ( )-swainsonine (247) from isopropylidene-D-erythrose (242) (Scheme 9.52). Wittig reaction of the acetonide 242 led to the (Z) alkene 252 in 86% yield. The chloro alcohol 252 was converted to the azide 253 in 76% yield, which subsequently underwent 1,3-dipolar cycloaddition, isomerization and hydroboration-oxidation to give the indolizidine 255 in 70% overall yield. Cleavage of the acetonide unit in 255 using 6 N HCl gave the target molecule 247 in 85% yield. 

Coupling the hydroboration with a subsequent oxidation of the new formed borane yields a //-Markovnikov alcohols. The hydroboration/oxidation sequence constitutes a powerful method for the regio- and stereoselective synthesis of alcohols. 

The starting material for the present synthesis was Wieland-Miescher ketone (24), which was converted to the known alcohol (25) by the published procedure [10], Tetrahydropyranylation of alcohol (25) followed by hydroboration-oxidation afforded the alcohol (26), which on oxidation produced ketone (27). Reduction of (27) with metal hydride gave the alcohol (28) (56%). This in cyclohexane solution on irradiation with lead tetraacetate and iodine produced the cyclic ether that was oxidized to obtain the keto-ether (29). Subjection of the keto-ether (29) to three sequential reactions (formylation, Michael addition with methyl vinyl ketone and intramolecular aldol condensation) provided tricyclic ether (30) whose NMR spectrum showed it to be a mixture of C-10 epimers. The completion of the synthesis of pisiferic acid (1) did not require the separation of epimers and thus the tricyclic ether (30) was used for the next step. The conversion of (30) to tricyclic phenol (31) was... 

The structure of baloxine (236) has been confirmed by partial synthesis from vindolinine,110 which has previously been converted into 19-hydroxytabersonine (237). The tetrahydropyranyl ether (238) of the (19.S)-epimer, on hydroboration-oxidation, gave a mixture of C-14 epimeric alcohols (239) on oxidation and removal of the tetrahydropyranyl ether grouping, these gave baloxine (236) (Scheme 34). Its formulation as (19S)-hydroxy-14-oxovincadifformine is thus confirmed. 

A synthesis of a-lipoic acid and derivatives has been reported. The pendant alkene of complex (111) was transformed to a primary alcohol (112) via hydroboration-oxidation sequence. Mitsunobu coupling of (112) with thiobenzoic acids to give (113), followed by desilylation and nucleophilic substitution again employing thiobenzoic acid gave the advanced intermediate (114) (Scheme 169). 

The hydration of alkenes via hydroboration-oxidation, developed by Herbert C. Brown (1912-2004 Nobel Prize, 1979) and coworkers, provides a valuable tool for the synthesis of a wide variety of alcohols of predictable regio- and stereochemistry. 

Details have been published of the total syntheses of velbanamine, isovel-banamine, cleavamine, 18/3-carbomethoxycleavamine, and catharanthine. Rosen-mund s route to the iboga alkaloids has now been appropriately modified to yield ibogamine and ibogaine, in addition to epi-ibogamine, and details of this work are also available. Hydroboration-oxidation of (227), presumably obtained by a thio-Claisen rearrangement [cf. (200)- (201)] affords the alcohol (228) which is a key intermediate in a Kutney-type synthesis of cleavamine however, details of the synthesis are not yet available. ... 

S-Hydroxytabersonine (108), in another series of transformations, has been used in a partial synthesis of baloxine (352), an alkaloid of Melodinus balansae. Protection of the hydroxyl group in 108 as its tetrahydropyranyl ether 353, followed by regiospecific hydroboration-oxidation, gave a mixture of epimeric C-14 alcohols (354) that, on oxidation and removal of the tetrahydropyranyl group, gave baloxine (352), whose structure as 19S-hydroxy-14-oxovincadifformine is thus confirmed (241) (Scheme 17). 

The Mitsunobu reaction has been used by It6 and co-workers as a key step in the synthesis of unnatural (+)-a-skytanthine (184) (196). The chiral amide 210 (197) was subjected to an aza-Claisen rearrangement, and the resulting amide 211 was reduced with LiAlU to afford the amine 212 in 80% yield. A hydroboration-oxidation sequence led to a mixture of amino alcohols 213, which was heated at 100°C for 24 h in the presence of cyanomethylene-trimethylphosphorane (CMMP) to yield a 92 8 mixture of cis- and rrans-fused isomers 214 and 215 in 81% yield from 212. 

Among the pinene-derived mono-alcohols, only (-)-isopinocampheol [(— )-33] has been used as an auxiliary. Its enantiomer ( + )-33 is commercially available or is readily prepared by a hydroboration/oxidation sequence from (+)-a-pinene (for a detailed procedure, see ref 34). The phenyl ether of (—)-33 has been used as a starting material for cyclic enol ethers 35. obtained by Birch reduction of the phenyl group3s, which are used as chiral dienes in Diels-Alder reactions (Section D.1.6.1.1.1.), although no description of the synthesis of the ether has been given. The alcohol has also been used for the synthesis of di(isopinocampheyloxy)-2-propenylborane 3433 (Section D.2.3.5.). 

This functionalization has been used for a synthesis of cortisone from cor-texolone that is an attractive alternative to biological hydroxylation. Thus irradiation of (5) and lodobenzene dichloride gives, after dehydrohalogenation and saponification, the unsaturated alcohol (6). Hydroboration, oxidation, and deprotection of (6) affords dihydrocortisone, which had been converted previously into cortisone acetate and prednisolone acetate. 

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