Homoallyhc alcohols

Aldehydes react with alkenylborates to give 1,3-diols upon oxidation of the intermediate (300). Alkynylborates ate transformed by epoxides into homoallyhc alcohols and alkenylborates into 1,4-diols (300,301). Carbon dioxide reacts with alkenylborates to yield catboxyhc acids (302). The scope of these transformations is further extended by the use of functionalized electrophiles and borates, often reacting with high stereoselectivity. For example, in the... 

A novel lactone and lactol synthesis was achieved by Cossy and coworkers [268], usinga CM followedby ahydrogenationandaringclosure. Ina typical procedure, aso-lution of acrylic acid or acrolein and an allylic or homoallyhc alcohol is stirred at room temperature under 1 atm of H2 in the presence of the ruthenium catalyst 6/3-16a and Pt02. Under these conditions, the homoallylic alcohols 6/3-101 (n= 1) and acrylic acid 6/3-102 led to the lactones 6/3-103 and the reduced alcohol 6/3-104 with acrolein, the corresponding lactols were obtained, together with 6/3-104 (Scheme 6/3.30). 

The approach to polyketide synthesis described in Scheme 5.2 requires the relatively nontrivial synthesis of acid-sensitive enol acetals 1. An alternative can be envisioned wherein hemiacetals derived from homoallylic alcohols and aldehydes undergo dia-stereoselective oxymercuration. Transmetallation to rhodium could then intercept the hydroformylation pathway and lead to formylation to produce aldehydes 2. This proposal has been reduced to practice as shown in Scheme 5.6. For example, Yb(OTf)3-cata-lyzed oxymercuration of the illustrated homoallyhc alcohol provided organomercurial 14 [6]. Rhodium(l)-catalyzed hydroformylation of 14 proved successful, giving aldehyde 15, but was highly dependent on the use of exactly 0.5 equiv of DABCO as an additive [7]. Several other amines and diamines were examined with variation of the stoichiometry and none proved nearly as effective in promoting the reaction. This remarkable effect has been ascribed to the facilitation of transmetallation by formation of a 2 1 R-HgCl DABCO complex and the unique properties of DABCO when both amines are complexed/protonated. 

The allylation reaction between ketones and allylsilanes was achieved in 2005. Yamamoto and Wadamoto developed the asymmetric allylation reaction in the presence of AgF-Difluorphos (Scheme 9.6).12 The reaction of ketones and allyltrimethoxysilane in the presence of AgF and Difluorophos afforded the corresponding tertiary homoallyhc alcohols with high enantioselectivities. Additionally, a,(3-unsaturated ketones could be used as substrates, and this catalytic system could be applied for the asymmetric crotylation reaction to obtain anti adducts preferentially (Schemes 9.7 and 9.8). When a,p-unsaturated ketones were used as substrates, 1,2-addition products were obtained exclusively. As described before, the anti adducts were obtained predominately, regardless of the geometry of crotyltrimethoxysilane. 

Barrett and Lebold used the Brown asymmetric crotylation to prepare the homoallyhc alcohol 22 in the total synthesis of nikkomycin B 21, a natural product that exhibits fungicidal, insecticidal, and acaricidal activities14 (Scheme 3.1k). 

The six-membered transition state for the reaction of an allylic borane or boronate is very reminiscent of the cyclic transition state for the aldol reaction you met in Chapter 34. In this case the only change is to replace the oxygen of the enolate with a carbon to make the allyl nucleophile. The transition state for the aldol reaction was a chair and the reaction was stereospecific so that the geometry of the enolate determined the stereochemistry of the product aldol. The same is true in these reactions. B-Crotyl boranes (or boronates) give anti homoallyhc alcohols and Z-crotyl boranes (or boronates)... 

Consecutive treatment of an allylic stannane with SnCl4 and hexanal derivative provided the corresponding homoallyhc alcohol. Subsequent cyclization of this alcohol, promoted by phenylselenyl chloride and tin chloride, followed by reduction with Bu.Sri 11 afforded a disubstituted tetrahydrofuran as a single stereoisomer. Repetition of this procedure enabled access to pamamycin 607 which has three 2,5-cis-disubstituted tetrahydropyran moieties (Scheme 12.19) [54]. 

Asymmetric allyation of carbonyl compounds to prepare optically active secondary homoallyhc alcohols is a useful synthetic method since the products are easily transformed into optically active 3-hydroxy carbonyl compounds and various other chiral compounds (Scheme 1). Numerous successful means of the reaction using a stoichiometric amount of chiral Lewis acids or chiral allylmetal reagents have been developed and applied to organic synthesis however, there are few methods available for a catalytic process. Several reviews of asymmetric allylation have been pubHshed [ 1,2,3,4,5] and the most recent [5] describes the work up to 1995. This chapter is focussed on enantioselective allylation of carbonyl compounds with allylmetals under the influence of a catalytic amount of chiral Lewis acids or chiral Lewis bases. Compounds 1 to 19 [6,7,8,9,10,11,12,... 

If the carbanion of (1) is allowed to react with an aldehyde or ketone, 3-hydroxy aldehydes can be prepared. Since 3-hydroxy aldehydes are usually labile, it is advantageous to trap the adduct (a) with chloromethyl methyl ether as shown for (5). The protected hydroxy aldehydes (6) so obtained can be converted into homoallyhc alcohols by a Wittig reaction. 

In a separate investigation by Porco, Jr. and coworkers, the isatin derivative 134 (R = H) was converted to spirooxindole pyran 141 in 13 1 dr and 99% ee by means of a Prins-type cyclization involving homoaUyhc alcohol 140 [79]. The diastereos-electivity of the transformation has been proposed to arise from a preferred chairlike transition state with the benzenoid ring of oxindole in a pseudoequatorial orientation. Spirooxindole oxepenes also were prepared via diastereoselective spiro-annulation of isatins with bis-homoallyhc alcohols. 

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

Kabalka et al. have investigated the Pd-catalyzed eross-eoupling reaction of MBH acetates and bis(pinacolato)diboron to produee 3-substituted-2-alkoxy-carbonyl allylboronates 371, whieh ean be further transformed into stable allyl trifluoroborate salts 372 by addition of exeess aqueous KHF2. The allylboronate 371 and allyltrifluoroborate derivatives 372 react with aldehydes to afford functionalized homoallyhc alcohols 373 and 374, respectively, stereoselectively in the presence of Lewis acid (Scheme 3.166). ... 

As shown in Scheme 14.6, this novel domino sequence could indeed be realized [12]. It was found that optimized conditions for the selective generation of the l,3-sy -dioxane products involved treatment of homoallyhc alcohol 10 in acetaldehyde (19) as co-solvent with a slight excess of potassium hexamethyldisi-lazide (KHMDS) (1.5 equiv) and catalytic amounts (10 mol%) of [Pd(allyl)Cl]2 and PPhg (30 mol%), and conducting the reaction in toluene at room temperature. 

In the presence of bismuth(lll) chloride-aluminum, allylic bromides have been found to react with aldehydes at room temperature in tetrahydrofuran-water to afford the corresponding homoallyhc alcohols in high yields (Wada et al, 1987). Water was found to play a crucial role since the allylation failed in pure tetrahydrofuran. Only a catalytic amount of bismuth chloride was needed to carry out the reaction. Bismuth(ill) chloride was reduced by aluminum to zero-valent bismuth, which could insert into the carbon-bromine bond of the allylic bromide to afford an allylbismuth intermediate as the reactive species. The allylation reaction could occur with the couple Bi(0)-Al(0) in tetrahydrofuran-water only in the presence of a catalytic amount of hydrobromic acid (Wada et al, 1990). Since bismuth(O) was postulated to be an intermediate oxidation state, the reaction was accomplished via an electrochemical redox pathway (Figure 4.1) in a two-phase system (Minato and Tsuji, 1988). Reactions mediated by Bi(0) as the only promotor were sluggish (Wada et ah, 1990). An exception was, however, reported with the coupling between p-nitrobenzaldehyde and allyl iodide in water (Chan and Isaac, 1996). 

The allyl transfer chemistry is applicable to the synthesis of aryl-substituted vinylic and allylic sUanes of synthetic importance [17]. Homoallyhc alcohol bearing a ferf-butyldimethylsUyl group at the allylic position participates in the allyl transfer to yield ( )-3-aryH-alkenylsilanes (Scheme 5.17). The transition state of the retro-allylation should have the bulky silyl group at the equatorial position, accounting for the -stereoselectivity. 

Yamamoto took a similar approach for the epoxidation of allyUc and homoallyhc alcohols (Schane 4.20). This process employed chiral hydroxamic acid ligand 101 to induce stereocontrol and VO(OtPr)3 to serve as the Lewis acid [49]. ( )-HomoaIlyhc alcohol 102 was converted to epoxide 103... 

Alternatively, Mootoo and coworkers [82,83] have developed a two-step iodoether-ification/Ag-catalyzed cychzation method for the synthesis of spiroacetals from homoallyhc alcohols 150 (Scheme 37). Treatment of the diol with iodonium dicollidine perchlorate (IDCP), followed by exposure to silver triflate in the presence of collidine affords the spiroacetals 154 in moderate to good yield as diastereomeric mixtures. This method was most recently applied in their synthesis of a simplified monensin analogue, polyether spiroacetal 156 [84]. Thus, two-step treatment of diol 155 under the established conditions provided spiroacetal 156 as a 2 1 mixture of epimers. 

General experimental procedure for Yamamoto epoxidation of homoallylic alcohols To a mixture of hydroxamic acid 21 (0.02 mmoi) and toiuene (0.25 mL) at room temperature was added VO(0/-Pr)3 (0.01 mmol). The mixture was stirred at room temperature for 8hours. After that time, 88% cumene hydroperoxide (1.5 mmol) was added, followed by homoallyhc alcohol (l.Ommol). The reaction mixture was stirred for 24 hours and then quenched by the addition of trimethyiphos-phite (1.5 mmol). The mixture was extracted with ethyi acetate. The combined organic layers were dried over Na2S04, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gei to give the desired epoxide. 

SCHEME 35.9. The asymmetric epoxidation of homoallyhc alcohols in the synthesis of the potent tachykinin receptor antagonists 35 and 36. 

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