Homoallylic alcohols reduction

The complexes may be applied to some very demanding and complex transformations as illustrated by a key step in the synthesis of Bafilomycin A1 (Scheme 9), in which a neutral rhodium catalyst was employed69. In contrast, a cationic iridium-based complex was the catalyst of choice in an exacting selective homoallylic alcohol reduction to achieve a vital inversion of configuration in the synthesis of Brevetoxin B70. Functionalized alkenes may also be effectively reduced, significantly trialkylstannanes which... 

An unprecedented nickel-catalyzed reductive coupling between an epoxide and an alkyne to give synthetically useful homoallylic alcohols has been developed by Jamison [55a], and was recently used in a short enantioselective synthesis of am-... 

One of the most gentle methods for the generation of reactive allylmetallic reagents was introduced in 1977 by Hiyama and Nozaki1,2,3,33. By the action of two equivalents of chromi-um(II) chloride on allylic halides in tetrahydrofuran at 0°C in the presence of a carbonyl compound, reductive coupling with the formation of a homoallylic alcohol takes place. 

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

The grem-dibromocyclopropanes 152 bearing a hydroxyalkyl group, prepared by the addition of dibromocarbene to allylic or homoallylic alcohols, undergo an intramolecular reductive carbonylation to the bicyclic lactones 153. bicyclic lactone derived from prenyl alcohol is an important precursor for the synthesis of ris-chrysanthemic acid. (Scheme 54)... 

Homoallylic alcohols (8, 111-112). CrCl2, prepared in situ by reduction of CrCl, (Strem) in THF with Na/Hg, is superior to CrCl2 prepared by reduction of CrCl, with LiAlHj for the Cr(II)-mediated addition of crotyl halides to aldehydes. The homoallylic alcohols are formed in good yield and with high arm-selectivity.7 Example ... 

The Barhier-type reaction of aldehydes and ketones with allyl halides (485) in the presence of Sml2, leading to homoallyl alcohols (486), has received recent interest as a one-step alternative to the Grignard reaction. However, the reactions require the use of stoichiometric amounts of the reducing Sm(III) species. Recently, the electroreductive Barhier-type allylation of carbonyl compounds in an SmH-mediated reaction has been developed [569]. The electrolysis of (485) is carried out in a DMF-SmCl3-(Mg/Ni) system in an undivided cell to give the adduct (486) in 50 85% yields (Scheme 168) [569]. Electrosynthesis of y-butyrolactones has been achieved by the reductive coupling of ethyl 3-chloropropionate with carbonyl compounds in the presence of a catalytic amount of SmCfi [570]. 

Coupling ofallylic acetates with ketones homoallylic alcohols In the presence of Pd[P(C6H5)3]4, Sml2 effects reductive coupling of allylic acetates with ketones to form homoallylic alcohols in 50-95% yield. 

Looking first at alcohol-directed reductions62, it is apparent that there have been many studies of the reduction of allylic and homoallylic alcohols using both the neutral and cationic reduction complexes based on rhodium, iridium etc. In the case of cyclic substrates where an alcohol is located on one side of a ring, the hydrogen is simply delivered cis to the alcohol function63. This is illustrated by key reduction steps in the synthesis of monensin (Scheme 5)64 and the marine natural product arenarol (Scheme 6)65. In each... 

Reduction of — C C(CH1),OH.2 Lithium bronze is the most effective reagent for conjugate reduction of homopropargylic alcohols to homoallylic alcohols.. 

Ni alkoxide as a stoichiometric reaction. However, in this reaction the silylnickel alkoxide 76 is formed, and its reductive elimination affords silyl ethers 77 and 78. At the same time, Ni(0) is regenerated to make the reaction catalytic. The formal total synthesis of elaeokanine C (79) was carried out by this reaction [25], Homoallylic alcohol 81 is obtained by the intermolecular reaction of benzaldehyde with the diene 80 and hydrosilane in high regio- and stereoselective manner [26],... 

A regio- and stereoselective formation of homoallylic alcohols and amines has been realized by the reaction of easily available allylic acetates 213 and 217 with bispinacolatodiboron 149 in the presence of palladium catalysts followed by the addition of aldehydes/imines (Scheme 36) <2005EJO2539>. The mechanism involves the formation of an 7]3-allyl-Pd complex, which inserts between B-B bond, and subsequent reductive elimination to yield the allyl... 

At this juncture, Danishefsky decided to investigate the possibility of setting the C(ll) and C(17) methyl stereocentres of 23 by hydroxyl-directed hydrogenation.13 Some years earlier, Evans had shown that cationic rhodium- and iridium-phosphine complexes can mediate highly diastereoselective reductions of trisubstituted homoallylic alcohols. However, for excellent stereoselectivities to generally be observed, it... 

The following reactions proceed with the participation of the allylic boron system (i) allylboration and protolytic cleavage of organic compounds with multiple bonds, (ii) allylboron-alkyne condensation,598 599 (iii) reductive mono-and trans-a,a -diallylation of nitrogen aromatic compounds, (iv) disproportionation processes between tribut-2-enylborane and BX3 (X = C1, Br, OR, SR). Allylboration of carbonyl compounds, thioketones, imines, or nitriles leads to the homoallylic alcohols, thiols, or amines (Equations (136) and (137). It is most important that 1,2-addition to aldehydes and imines proceeds with high diastereoselectivity so that ( )-allylic boranes and boronates give the anti-products, while -products are formed preferentially from (Z)-isomers. 

Brown s crotylboration protocol was used effectively in the synthesis of azu-mamide A 28. Azumamides are unusual cyclic peptides that show potent inhibitory activity on histone deacetylase enzymes. A highly diastereo- and enan-tioselective (dr >99% 98% ee) crotylation of 3-benzyloxypropanal with the chiral reagent ( >crotyl-1Ipc2borane (l19E) afforded the homoallylic alcohol 29. Subsequent reductive ozonolysis and K2CO3-mediated hydrolysis of the acetate furnished the diol 3016 (Scheme 3.1m). 

As depicted in the following scheme, a homoallyl alcohol derived from a norbomyl a-diketone underwent a lead(IV) acetate reaction in MeOH, resulting in the formation of a novel methoxy substituted spirocyclic tetrahydrofuran <07CC4239>. It is believed that the addition of the methoxylead(IV) acetate species across the alkene from the less sterically hindered side to form a plumbonium cation leads to the major product after subsequent cyclization and reductive elimination. Moreover, construction of tetrahydrofurans by a Pd(II)/Pd(IV)-catalyzed aminooxygenation of homoallyl alcohols was also reported <07AGE5737>. 

Acylation of the homoallylic alcohol 11 derived from a stannane and 3-phenylpropanal and a subsequent SmI2-promoted reductive cyclisation provides high yields of cA-2,6-disubstituted 2-methoxy-4-methylidenetetrahydropyrans. The methodology has been utilised to synthesise a... 

A common intermediate, a 2-sulfonyltetrahydropyran derived from a protected homoallylic alcohol, is used to obtain both the cis and trans isomers of 2,6-disubstituted tetrahydropyrans. Deprotonation followed by an alkylation and reduction sequence affords the former, while ionisation using AICI3 and subsequent reaction with a nucleophile leads to the latter isomer (Scheme 10). The bis-tetrahydropyran portion of phorboxazole has been constructed using this chemistry <07AG(E)6874>. 

---