Homoallylic derivatives complexes

Starting from 2,4,6-octatriene and pivaldehyde, the conjugated homoallylic alcohol 8 is obtained as the sole product. Cycloheptatriene-derived complexes react with aldehydes and C02 to afford mixtures of the isomeric 1,3- and 1,4-cycloheptadienyl carbinols or acids, respectively. Interestingly, analogous reactions with methyl chloroformate or dimethyl carbamoyl chloride produce the conjugated dienyl ester 9 or amide 10 as unique products [19,20]. 

Nucleophilic attack occurs at C(2) of the diene. The 1,3-cyclohexadiene complex 66 is converted to the homoallyl anionic complex 67 by nucleophilic attack, and the 3-alkyl-1-cyclohexene 68 is obtained by protonation. Insertion of CO to 67 generates the acyl complex 69, and its protonation and reductive elimination afford the aldehyde 70 [20]. Reaction of the butadiene complex 56 with an anion derived from ester 71 under CO atmosphere generates the homoallyl complex 72 and then the acyl complex 73 by CO insertion. The cyclopentanone complex 74 is formed by intramolecular insertion of alkene, and the 3-substituted cyclopentanone 75 is obtained by reductive elimination. The intramolecular version, when applied to the 1,3-cyclohexadiene complex 76 bearing an ester chain at C(5), offers a good synthetic route to the bicyclo[3.3.1]nonane system 78 via intermediate 77 [21]. 

It was determined that carbon nucleophiles derived from carbon acids with p/fa > 22 or so are sufficiently reactive to combine with the diene ligand rapidly at —78°C to produce an anionic intermediate (Scheme 25). With a few exceptions, the regioselectivity favors formation of the homoallyl anionic complex from addition at C-2, by kinetic control. This intermediate can be quenched with protons to give the terminal alkene, or can react with excess CO to produce an acyl iron intermediate. Following the recipes of Collman s reaction, the acyl iron intermediate can lead to methyl ketones, aldehydes, or carboxylic acids. The processes are illustrated with the 1,3-cyclohexadiene complex (Scheme 25). ... 

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 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. 

Pancratistatln. The first total synthesis of ( )-pancratistatin (94) (Scheme 14), the structurally most complex of narciclasine alkaloids, was achieved by Danishefsky [27]. The requisite starting material, the substituted benzaldehyde 95 prepared from pyrogallol in six steps in 18% overall yield, was converted via the homoallylic alcohol 96 into the diene 97. Reaction of 97 with 2-nitrovinylsulphone yielded the cycloadduct 98, which on treatment with tributyltinhydride and 2,2 -azobisisobutyronitrile furnished the cyclohexadiene 99. Whilst the cyclisation of the silylether 99 or the derived phenol, under the influence of iodine, could not be accomplished, the more nucleophilic stannylether did participate in the desired ring closure and provided via the iminium salt, the iodolactone 100 on aqueous work-up. 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

Spirocyclic 4-substituted tetrahydropyrans are readily obtained through the Prins reaction involving cyclic ketones, homoallylic alcohols and MeS03H <02H(58)659>. The cationic species generated when alkyne-Co complexes derived from 8-valerolactone are treated with SnCl4 undergo a double cyclisation to yield the oxaspiro[5.5]undecane <02T2755>. 

The indium-mediated reaction of cinnamyl bromide with 5-formyluracil derivatives gives the corresponding homoallylic alcohols (Equation (21)). The presence of G4 carbonyl is essential for high diasteroselection owing to the complexation with indium.182... 

Similarly, Takahashi and coworkers reported that treatment of alkynes with zirconocene-ethylene complex (9) and homoallylic bromides gave allylcyclo-propane derivatives [21]. Therefore, the possibility of y-elimination of the halogen atom in zirconacyclopentene intermediates appeared to be more general as expected. The plausible mechanism is shown in Scheme 13. Carbozirconation... 

As with the corresponding allylboronate, the enantioselectivity of reactions with (3-alkoxy and conjugated aldehydes are lower (55-74% ee). In the case of benzaldehyde (91%, 66% ee), selectivity can be improved by the use of the derived chromium tricarbonyl complex. The homoallylic alcohol is obtained after... 

Carbonyl Allylation and Propargylation. Boron complex (8), derived from the bis(tosylamide) compound (3), transmeta-lates allylstannanes to form allylboranes (eq 12). The allylboranes can be combined without isolation with aldehydes at —78°C to afford homoallylic alcohols with high enantioselectivity (eq 13). On the basis of a single reported example, reagent control might be expected to overcome substrate control in additions to aldehydes containing an adjacent asymmetric center. The sulfonamide can be recovered by precipitation with diethyl ether during aqueous workup. Ease of preparation and recovery of the chiral controller makes this method one of the more useful available for allylation reactions. 

Reaction of alkenes with carbonyl compounds or carbonyl derivatives in the presence of Lewis acids, the ene reaction, enables the stereoselective preparation of highly functionalized compounds. Copper Lewis acids activate both aldehydes and imines in ene reactions. Evans has reported that Cu(II) Lewis acids catalyze glyoxylates in reactions with alkenes (Sch. 56) [103]. The homoallylic alcohols 257 and 259 are produced in high yield and enantioselectivity. The bis aquo complex 260 is a readily prepared and air-stable catalyst and gave high chemical yield and excellent selectivity in the ene reactions. Another point of note is that catalysts 260 and 261 furnish enantiomeric products even though they differ from each other only by the substituent at the 4-posi-tion of the oxazoline. 

The regio- and stereoselective zirconocene-catalyzed addition of alkylmagnesium halides to alkenes, a process which has been described previously (see Section 7.5.2, Scheme 7-79) was investigated with ethylene-l,2-bis( M,5,6,7-tetrahydroind-l-enyl)zirconium dichloride [(EBTHI)ZrCl2l) [118] as chiral zirconocene. Thus, treatment of the latter with alkylmagnesium halides leads to the formation of the derived zirconocene-alkene complex 88, characterized by NMR [119], which reacts with cyclic ethers or amines to lead to the corresponding homoallylic alcohol or amine, respectively, in > 95% ee and good overall yield [120] (Scheme 7-103). 

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