Synthesis of Homoallylic Alcohols

RCHO + BrCHjCHCHj Zn-NH CI rch(OH)CH2CH=CH2 Aldehyde 3-Bromopropene Homoallylic alcohol 

The B-allyl-9-BBN derivatives react with carbonyl compounds to afford borinate esters, which on protonolysis using triethanolamine afford the corresponding homoallylic alcohols. Consequently, the allylboration sequence provides a synthetically useful alternative to the familiar Grignard s synthesis of these alcohols. However, the protonolysis by triethanolamine causes a problem in the isolation of homoallylic alcohol from the thick, air-sensitive, boron-containing mixture. Fortunately, treatment of pentane solution of borinate esters of 9-BBN with 1 equiv of ethanolamine results in the rapid formation of a fluffy white precipitate of ethanolamine 9-BBN adduct, which can be easily removed (Eq. 6.7) [1]. 

Allylboration of aldehydes and ketones with B-crotyl-9-BBN affords only the rearranged product (Eq. 6.8 Table 6.7) [1]. Monomeric formaldehyde gives 2-methyl-3-buten-1 -ol. 

Unsymmetrical allylboranes (prepared from allenes or 1,3-dienes) when treated with acetone give only the rearranged homoallylic alcohol (Table 6.8) [1]. 

The allylboration offers certain advantages over the familiar Grignard route for preparation of homoallylic alcohols  

Certain functionalities like halides can be tolerated allylboration with unhindered aldehydes and ketones are far faster than those with esters and amides. The former groups are readily allylborated in the presence of latter. 

---

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. 

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). 

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. 

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. 

Homoaliyttc alcohols,An efficient synthesis of homoallylic alcohols of type I involves carbometallation of 1-alkynes (8, 506) followed by reaction of the alkcnyl-aluminate (a) with an epoxide.2... 

A highly selective synthesis of homoallylic alcohols has been reported by Tietze et al.,917 who reacted methyl ketones, the chiral norpseudoephedrine derivative 285, and an allylsilane in the presence of a catalytic amount (0.2 mol%) of triflic acid [Eq. (5.340)]. The transformation was interpreted as an SN2 attack of the allylsilane to the protonated mixed acetal 286. The obtained ethers were then cleaved to the final product, homoallylic alcohols. 

Since the 1980s, chemists have attempted to develop novel Lewis acids and Lewis bases able to catalyze the Sakurai reaction with full diastereo- and enantiocontrol. A review by Denmark and Fu [19] summarizes the most recent advances in this area. Thus, we will not discuss these aspects of the Sakurai reaction but shall focus our attention on the one-pot three-component synthesis of homoallylic alcohols and ethers. 

The [2,3]-Wittig Rearrangement allows the synthesis of homoallylic alcohols by the base-induced rearrangement of allyl ethers at low temperatures. 

An aluminium-catalysed tandem Claisen-ene sequence has been developed for the synthesis of homoallylic alcohols (89) and thence a-methylene-y-butyrolactones (90) in good overall yields. Extensive investigation has revealed that Et2AlSPh catalyses Claisen rearrangement of ft -substituted allyl vinyl ethers (85) into 0,5-aluminium... 

Synthesis of homoallylic alcohols containing two chiral centres... 

The ability of allyltin halides to extend their coordination sphere allowed the preparation of chiral hypervalent complexes with diamine ligands, which have been efficient in the asymmetric synthesis of homoallylic alcohols with up to 82% ee100. Similarly, a chiral hypervalent allyltin was prepared from a low valent tin (II) catecholate, chiral dialkyl tartrate and ally lie halide101. The allylation of aldehydes and activated ketones proceeded with high enantiomeric excess. Allyltins prepared from Lappert s stannylene and allylic halides were shown to be efficient as well, although the Lewis acid character of the tin atom is much less marked in that case102,103. 

Carbonyl allylation using pentacoordinate allylsilicates is valuable for stereospecific synthesis of homoallyl alcohols ... 

Thus allylboration of carbonyl compounds with B-allylic derivatives of 9-BBN, followed by transesterification with ethanolamine, provides a simple, convenient method for the synthesis of homoallylic alcohols 98). 

Chiral homoallylic alcohols, The glycol 1 has been used as the chiral matrbt in an enantioselective synthesis of homoallylic alcohols (4) from aldehydes and allyl-boranes (equation I). 

Thus ailylboration of carbonyl compounds with B-allylic derivatives of 9-BBN, followed by transesterification with ethanolamine, provides a simple, convenient method for the synthesis of homoallylic alcohols It has been reported that enantiomerically enriched allylic boranes provide homoallylic alcohols with high degree of enantio- and diastereoselectivity. The scheme is illustrated in Eqs. 48 and 49... 

Addition of allylmetal compounds to aldehydes synthesis of homoallylic alcohols 864... 

Perfect anti selectivities may also result where they would not have been predicted on the basis of much less satisfactory model studies (cf. Table 5, entries 1 and 9). Pertinent examples are the Wittig rearrangements of the sterically demanding acid (85 equation 20) or of the oxazoline (87 equation 21). ° The highly syn,as selective synthesis of homoallylic alcohols (26) from isopropyl esters was discussed earlier in a different context (equation 12, Scheme 3). ... 

Faller, J. W., Sams, D. W. I., Liu, X. Catalytic Asymmetric Synthesis of Homoallylic Alcohols Chiral Amplification and Chiral Poisoning in a Titanium/BINOL Catalyst System. J. Am. Chem. Soc. 1996,118, 1217-1218. 

Okude, Y., Hirano, S., Hiyama, T., Nozaki, H. Grignard-type carbonyl addition of allyl halides by means of chromous salt. A chemospecific synthesis of homoallyl alcohols. J. Am. Chem. Soc. 1977, 99, 3179-3181. 

Hoffmann, R. W., Herold, T. Enantioselective synthesis of homoallyl alcohols via chiral allylboronic esters. Angew. Chem. Int. Ed. 1978,17, 768-769. 

---