Allylation chelation control

Chelation control was postulated for the reaction between 2,3-[isopropylidenebis(oxy)] propanal and allyl iodide/stannous fluoride which proceeded with useful erythro selectivity92. 

The results show that modest chelation control can be obtained using organomctallics like allylmagnesium chloride, chloromagnesium allyltriethylaluminate and allylzinc bromide, which are capable of /1-chelation. In contrast to this, 9-allyl-9-borabicyclo[3.3.1]nonane (9-allyl-BBN)... 

The predominant formation of 16 is consistent with a chelation-controlled allyl addition as shown in 18, with attack occurring from the more readily accessible. 57-face. 

For enolates with additional functional groups, chelation may influence stereoselectivity. Chelation-controlled alkylation has been examined in the context of the synthesis of a polyol lactone (-)-discodermolide. The lithium enolate 4 reacts with the allylic iodide 5 in a hexane THF solvent mixture to give a 6 1 ratio favoring the desired stereoisomer. Use of the sodium enolate gives the opposite stereoselectivity, presumably because of the loss of chelation.61 The solvent seems to be quite important in promoting chelation control. 

Enolates of allyl esters of a-amino acids are also subject to chelation-controlled Claisen rearrangement.249... 

Allylic stannaries with y-oxygen substituents have been used to build up polyoxy-genated carbon chains. For example, 16 reacts with the stannane 17 to give a high preference for the stereoisomer in which the two oxygen substituents are anti. This stereoselectivity is consistent with chelation control.183... 

Reactions through chelated TS Reactions of a- or (3-oxy-substituted aldehydes often show chelation-controlled stereoselectivity with Lewis acids that can accommodate five or six ligands. Chelation with substituents in the allylic reactant can also occur. The overall stereoselectivity depends on steric and stereoelectronic effects in the chelated TS. 

Epoxides of allylic alcohols exhibit chelation-controlled regioselectivity.128... 

Normally, the addition of C-nucleophiles to chiral a-alkoxyaldehydes in organic solvents is opposite to Cram s rule (Scheme 8.15). The anti-Cram selectivity has been rationalized on the basis of chelation control.142 The same anti preference was observed in the reactions of a-alkoxyaldehydes with allyl bromide/indium in water.143 However, for the allylation of a-hydroxyaldehydes with allyl bromide/indium, the syn isomer is the major product. The syn selectivity can be as high as 10 1 syn anti) in the reaction of arabinose. It is argued that in this case, the allylindium intermediate coordinates with both the hydroxy and the carbonyl function leading to the syn adduct. 

In reactions of chiral aldehydes, TiIV compounds work well as both activators and chelation control agents, a- or A-oxygcnated chiral aldehydes react with allylsilanes to afford chiral homoallylic alcohols with high selectivity (Scheme 22).85 These chiral alcohols are useful synthetic units for the synthesis of highly functionalized chiral compounds. Cyclic chiral 0,0- and A/O-acetals react with allylsilanes in the same way.86,87 Allenylsilanes have also been reported as allylation agents. 

Synthesis of (—)-monatin (524), a high-intensity sweetening agent, was achieved by chelation-controlled cycloaddition of chiral oxazinone-derived nitrone (16 ) to allyl alcohol (520) in the presence of MgBr2 OEt2 (Scheme 2.248) (746). 

The synthesis of the smaller fragment methyl esters 144-147 was completed as depicted in Scheme 20. Chelation-controlled allylation of aldehydes 135-138 prepared by chromium(VI) oxidation of alcohols 122,123,133, and 134 with allyltrimethylsilane (139) in the presence of titanium(IV) chloride proceeded... 

The construction of the heterocycle 3 started with enantiomerically-pure ethyl lactate. Protection, reduction and oxidation led to the known aldehyde 6. Chelation-controlled allylation gave the monoprotected-diol 7. Formation of the mixed acetal with methacrolein followed by intramolecular Grubbs condensation then gave 3. The dihydropyran 3 so prepared was a 1 1 mixture at the anomeric center. 

The synthesis of the C20—C26 fragment started with a 4-alkylation of methyl aceto-acetate The first stereocentre was introduced by enantioselecuve catalytic hydrogenation with Noyort s (S)-binap rhodium complex (cf p 102f.) Stereoselective Frater-Seebach alkylation with allyl bromide introduced the second stereocentre in 90% yield (cf p 27) Stereospecifid introduction of the stereocentres C24 and C2 was achieved by a chelation controlled addition of an allylstannane to an aldehyde (see p 66f) After some experimentation with Lewis acid catalysts and reaction conditions a single diastereomer of the desired configuration was ob-... 

The cycloaddition of a nitrile oxide with a chiral allylic ether affords an isoxazoline with selectivity for the pre/-isomer. This selectivity increases with the size of the alkyl substituent and is insensitive to the size of the allyl oxygen substituent. However, allyl alcohols tend to form the / ar/ isomcr preferentially, although the selectivity is often low.427"434 The product of dipolar cycloadditions based on nitrile oxides, the isoxazoline moiety, can be converted into a large variety of functional groups under relatively mild conditions.3 Among other products, the addition can be used to prepare P-hydroxy ketones (Scheme 26.17).435 The isoxazoline moiety can be used to control the relative stereochemistry through chelation control.436,437... 

Recently, catalytic amounts of Lewis acids have been used in the reaction of allyllic tri- -butyltins with carbonyl compounds. Maruoka et al. report the remarkably chemoselective allylstannation of o-anisaldehyde over/>-anisaldehyde, catalyzed by BlCgFsL.1 z Piers et al. report that the chemoselectivity observed does not rely on classical chelation control. They conclude that stannylium ion pair [Bu3Sn(o-anisaldehyde)2]+[o-ArCH(allyl)OB(G6Fs)3] is the active species which is preferentially formed over the complex of/>-anisaldehyde with BlCgFsL (Equation (44)).143 Lambert et al. report a similar formation of stannyl cation from allyltri- -butyltin and trityl (CgFsLB-.144... 

The effect of proximal groups on the diastereoselectivity in the addition of allylindium to a carbonyl group has been extensively surveyed.153 When a- and /3-hydroxy aldehydes are subjected to the allylation, excellent diastereocontrol is realized, syn- 1,2-Diol and anti- 1,3-diol products are formed, respectively, at accelerated rates (Tables 1 and 2). Protection of the free hydroxy group results in the alternative formation of 1,2-anti products. High stereoselectivities have been observed for indium-promoted allylations of a- and /3-hydroxy aldehydes in aqueous media, implying that a chelate control still operates even in water.72,73,154-158... 

The effect of ionic liquid solvents on the stereochemical selectivity of allylation of 2-methoxycyclohexanone has been investigated, and found a higher selectivity (axial alcohol 34/equatorial alcohol 35) toward the chelation-controlled mechanism in ionic liquid than in conventional solvents such as water and THF. The use of 0.1 equiv. of indium, combined with Mn and TMSC1 (2 equiv. of each), results in the isolation of the desired products in good purity, with an overall conversion of 81% (Scheme 39).168... 

Gallium-mediated allylation of aldehydes or ketones in water gives the corresponding homoallyl alcohols in high yields without the assistance of either acids or sonication. The diastereoselectivity of the allylation of 2,3-dihydroxy-propanal depends on the solvent. When the reaction is carried out in water, the dominant product is the yy/z-isomer. In contrast, the anti-isomer is dominant when THF is employed. The yy/z-isomer may be regarded as the chelation-controlled product, due to the hydrogen bond between the two hydroxy groups. The aqueous environment favors... 

Similar results were obtained with chelation-controlled allylation mediated by radicals (Sch. 12) [28], In the presence of MgBr2 OEt2, the reaction of 2-iodoprop-ionate 29a with allyltributyltin 30 proceeded more readily even at a low temperature (-78 °C) than the reaction under reflux in hexane in the absence of the catalyst. The... 

Additions of the presumed /3-oxygenated allylic trichlorostannane to a-methyl, a-benzyloxy and /3-benzyloxy aldehydes are characterized by high reagent-controlled diastereoselectivity (Eq. 48) [70]. In the several examples examined aldehyde facial attack is little influenced by the resident chirality of the aldehyde. The result is particularly striking with the a-methyl aldehyde where the syn, syn adduct is the product of Felkin-Ahn addition and the anti, syn adduct is the anh-Felkin-Ahn or chelation-controlled adduct. 

---