Of homoallylic alcohol

Allyllic ether 53 is oxidized regioselectively to the /3-alkoxy ketone 54, which is converted into the a,/i-unsaturated ketone 55 and used for annulation[99]. The ester of homoallylic alcohol 56 is oxidized mainlv to the 7-acetoxy ketone 57[99]. 

These are usually obtained from the isomeric conjugated ketone, and are sometimes useful as intermediates, offering an alternative to enol derivatives. They may also be formed as a result of double bond introduction or by oxidation of homoallylic alcohols if so the conditions must be mild because they generally represent a less stable isomer. 

In contrast to the behavior of homoallylic alcohol (70a) when treated with methanesulfonyl chloride is pyridine, heating A -19-methanesulfonate (68b) in pyridine gives the 5)5,19-cyclo-6-ene (72). Vinylcyclopropane (72) is inert to the conditions used for converting vinylcyclopropane (73) to the A ° -B-homo-7)5-ol (70a). The latter results are only consistent with the existence of two discrete isomeric carbonium ion intermediates which give rise to isomeric elimination products. °... 

Hydroxy-l-alkenyl diisopropylcarbamates 2 (X = OCb), in this respect, occupy a medium position since they are stable in strongly acidic and basic protic solvents. For deblocking vinyl carbamates, the presence of catalytic amounts of mercuric or palladium(II) salts is required. Due to this stability, several reactions of homoallylic alcohols, proceeding with high diastereo-selectivity, e g., epoxidation, are applicable in order to introduce further hetero-substituents. 

Allylboron compounds have proven to be an exceedingly useful class of allylmetal reagents for the stereoselective synthesis of homoallylic alcohols via reactions with carbonyl compounds, especially aldehydes1. The reactions of allylboron compounds and aldehydes proceed by way of cyclic transition states with predictable transmission of olefinic stereochemistry to anti (from L-alkene precursors) or syn (from Z-alkene precursors) relationships about the newly formed carbon-carbon bond. This stereochemical feature, classified as simple diastereoselection, is general for Type I allylorganometallicslb. 

Z)-2-Butenylpotassium is generated from 4.5 mL (50 mmol) of (Z)-2-butene, 2.8 g (25 mmol) or /-BuOK. and 10.8 mL (25 mmol) oT 2.3 M butyllithium in THF for 15 min at —45 JC. This solution is cooled to — 78 C and 30 mmol of a 1 M solution of methoxy(diisopinocampheyl)borane in diethyl elher is added dropwise. The mixture is stirred for 30 min at — 78 °C, then is treated with 4mL (33 mmol) of boron trifluoride-diethyl ctherate complex this removes methoxide from the intermediate ate complex. This solution is immediatelv treated with 35 mmol of an afdchyde. Isolated yields of homoallylic alcohols are 63-79%. 

Allylboronates are attractive reagents for the highly diastereoselective ally-lation of carbonyl compounds. A sequential cross-metathesis-allylation reaction has recently been developed by Grubbs et al. [88c] and by Miyaura et al. [103]. The sequence is illustrated in Scheme 23 for the formation of homoallylic alcohol 114 from allylboronate 112, acetal 113, and benzaldehyde [88c]. 

An (E)-selective CM reaction with an acrylate (Scheme 61) was applied by Smith and O Doherty in the enantioselective synthesis of three natural products with cyclooxygenase inhibitory activity (cryptocarya triacetate (312), cryptocaryolone (313), and cryptocaryolone diacetate (314)) [142]. CM reaction of homoallylic alcohol 309 with ethyl acrylate mediated by catalyst C led (E)-selectively to d-hydroxy enoate 310 in near quantitative yield. Subsequent Evans acetal-forming reaction of 310, which required the trans double bond in 310 to prevent lactonization, led to key intermediate 311 that was converted to 312-314. 

Cho et al. reported a indium trichloride-catalyzed intramolecular Prins-type reactions of compounds having both the functionalities of homoallyl alcohol and acetal moiety. The intramolecular Prins cycliza-tions were performed using indium trichloride in chloroform or 25%... 

RajanBabu et al. have described an addition-elimination sequence employing vinyl stannanes for the preparation of homoallylic alcohols containing 5-membered rings [104],... 

The regiochemical control of Pd-catalyzed hydride transfer reaction is much more effective than that of the radical denitration, as shown in Eq. 7.98. The base-catalyzed reaction of nitroolefins with aldehydes followed by denitration provides a new synthetic method of homoallyl alcohols (Eq. 7.99).140 Exomethylene compounds are obtained by denitration of cyclic allylic nitro compounds with Pd(0), HC02H and Et3N (Eq. 7.100).140b... 

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). 

In 2001, the preparation of allylytterbium bromide and the synthesis of homoallylic alcohols using allylytterbium bromide were reported.39 393 Ytterbium metal was found to be activated by a catalytic amount of Mel at 0 °C in THF to produce allylytterbium bromide 66 (Equation (11)). The allylation reaction of a wide range of aromatic aldehydes and ketones proceeded at ambient temperature or less in good to high yields (Table 2). Imines also reacted with allylytterbium bromide to afford homoallyl amines (Table 3). 

Synthetic transformations of the products of the intramolecular bis-silylation have been examined. The five-membered ring products derived from homopropargylic alcohols were hydrogenated in a stereoselective manner (Scheme ll).90 Oxidation of the products under the Tamao oxidation conditions (H202/F /base)96 leads to the stereoselective synthesis of 1,2,4-triols. This method can be complementary to the one involving intramolecular bis-silylation of homoallylic alcohols (vide infra). 

In the case of tri-substituted alkenes, the 1,3-syn products are formed in moderate to high diastereoselectivities (Table 21.10, entries 6—12). The stereochemistry of hydrogenation of homoallylic alcohols with a trisubstituted olefin unit is governed by the stereochemistry of the homoallylic hydroxy group, the stereogenic center at the allyl position, and the geometry of the double bond (Scheme 21.4). In entries 8 to 10 of Table 21.10, the product of 1,3-syn structure is formed in more than 90% d.e. with a cationic rhodium catalyst. The stereochemistry of the products in entries 10 to 12 shows that it is the stereogenic center at the allylic position which dictates the sense of asymmetric induction... 

Scheme 13.1. Synthesis of homoallylic alcohols by addition of allylmetal compounds to aldehydes.

Efforts have been made to apply r 3-allyltitanium chemistry to the asymmetric synthesis of homoallylic alcohols and carboxylic acids. The synthesis and reactions of chiral r 3 -allyl-titanocenes with planar chirality, or containing Cp ligands with chiral substituents, have been reported [6c,15,30—32]. The enantiofacial selectivity in the allyltitanation reactions has been examined for the complexes 12 [15], 13 [30], 14 [31], 15, 16, and 17 [32] depicted in Figure 13.2. 

Tetrahydrofurans.s The (tributylstannyl)methyl ethers (1) of homoallylic alcohols (9, 475) on treatment with butyllithium undergo tin-lithium exchange to a-... 

P-Cleavage of homoallylic alcohols.1 Homoallylic tertiary potassium alkox-ides undergo cleavage in HMPT (or DMF) of the allylic C—C bond to give the enolate of a ketone (equation I). A rigid bicyclic system is not essential for the cleavage. 

The electrosynthesis of homoallyl alcohols (193) or 8-hydroxy esters (196) has been carried out by the reaction of methallyl chloride (190) (Scheme 75) or... 

A norpseudoephedrine auxiliary has been used to achieve >98% ee in the preparation of homoallylic alcohols from aliphatic alcohols and allylsilane. On-line NMR spectroscopy has been used to shed light on the mechanism, including a diversion that occurs if the temperature is not kept low enough. 

In an interesting reaction, reshuffling of functional groups can be achieved in the [RuCl2(PPh3)3]-catalyzed rearrangement of homoallylic alcohols (Scheme 9.2) [8,9]. Allyhc alcohols also react the same manner, however, when both kind of olefinic bonds are present in the same molecule, than it is the homoallylic moiety which reacts exclusively. 

A symmetric activation is also observed in the combination of (/f)-BINOL and Zr(0 Bu)4, which promotes enantioselective synthesis of homoallylic alcohols (Scheme 8.13). A 2 1 ratio of (/ )-BINOL and Zr(0 Bu)4 without any other chiral source affords the homoallylic alcohol product in 27% ee and 44% yield. Addition of (7 )-(+)-a-methyl-2-naphthalenemethanol ((/ )-MNM) leads to higher enantiomeric excess (53% ee) than those using only (7 )-BINOL. Therefore, (7 )-MNM can act as a chiral activator a higher ee can be achieved via activation of the allylation of benzaldehyde by addition of (7 )-MNM as a product-like activator. 

Figure 7. Preparation of homoallyl alcohol 15 via a Conforth-like transition state.

The first total synthesis of the marine macrolide leucascandrolide A relied upon the use of two key hydroformylahon reactions [25]. Yb(OTf)3-catalyzed oxymercuration of homoallylic alcohol 46 provided organomercurial 47, which was hydroformylated to give... 

In a recent paper, Zhang and Yamamoto have described a modified BHA ligand (235d) that is suitable for highly enantioselective vanadium-catalyzed epoxidation of homoallylic alcohols (Scheme 102). Both tram- and cA-substituted epoxides were achieved with nearly complete enantioselectivities and good yields. 

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