Chelation control also

Chelation control also occurs in the reaction of (S -benzyloxybutanal with the bis(enol) ether 2,3-bis(trimethylsilyloxy)-2-butene3. 

Exclusive trims attack of the nucleophile is also observed with 2,3-epoxycyclopentanones 1559. In contrast to 2-alkyl- and 2-methoxy-substituted cyclopentanones, preferential trans attack to 2,3-epoxycyclopenlanones occurs with alkyl, ethenyl, and ethynyl nucleophiles. Thus, there is no assistance by the epoxidic oxygen for cis attack. Due to the geometry of the molecule, chelation-controlled cis attack is not possible39 60. 

The lower diastereoselectivity found with aldehyde 15 (R = CH3) can be explained by the steric influence of the two methyl substituents in close vicinity to the stereogenic center, which probably diminishes the ability of the ether oxygen to coordinate. In contrast, a significant difference in the diastereoselectivity was found in the additions of phenyllithium and phenylmagnesium bromide to isopropylidene glyceraldehyde (17)58 (see also Section 1.3.1.3.6.). Presumably the diastereo-sclcctivity of the phenyllithium addition is determined by the ratio of chelation-controlled to nonchelation-controlled attack of the nucleophile, whereas in the case of phenylmagnesium bromide additional chelation with the / -ether oxygen may occur. Formation of the -chelate 19 stabilizes the Felkin-Anh transition state and therefore increases the proportion of the anZz -diastereomeric addition product. 

The extent of the stereoselectivity depends on the protection of the nitrogen and also on the catalyzing Lewis acid. However, the monoprolected a-amino aldehydes 1 (R3 = H) show good to excellent chelation-controlled syn preference, independent of the Lewis catalyst employed6fi S9. 

The fact that with acetal 1 (R1 = H R2 = CH3) a lower stereoselectivity is observed than with the acetals where R1 = Ft or C6II5 suggests that the bulkiness of the substituent at the acetal center also plays an important role in fixing the conformation of the transition state. With 1 bearing a hydrogen atom at the acetal center (R1 = II), the acetyl group is allowed to occupy the quasiequatorial position (3B) and the addition reaction therefore proceeds with no or only a weak chelation control. The same presumably holds for the elyoxal monoacetal 1 (Ri = R2 = M). 

Chelation control, as indicated in 5, is also a suitable model for rationalizing the stereochemical outcome of titanium tetrachloride mediated additions of 3,3-dimelhyl-2-trimethylsilyl-oxy-l-butenc (6) or l-methoxy-2-methyl-l-trimethylsilyloxy-l-propene (7) to 3-benzyloxy-2-methylpropanal (4). In both cases, there is almost exclusive formation of the chelate-controlled product (95 5 and >97 3, respectively)13. 

The Mukaiyama variation of the aldol reaction also allows 1,3-induced chelation control. Thus, the reaction of the enolsilane or silylketene acetal with (5 )-3-benzyloxybutanal results in both cases in the predominant formation of the cwt/ -adduct (92 8 and 90 10), respectively14. 

These results may be explained by a chelation-controlled mechanism A with M representing a complex of JVtg(ll), Ce( 111) or of both cations. The highly stereoselective addition of the organocop-per reagent can be rationalized either by the dipolar model B or the Felkin-Anh model C (see also ref 12). 

With a- and (3-benzyloxyaldehydes, the /-butylthio ketene acetals also gave chelation-controlled addition.91... 

Entry 10 is an example of the application of chelate-controlled stereoselectivity using TiCl4. Entry 11 also involves stereodirection by a (3-O-methoxybenzyloxy) substituent. In this case, the BF3-catalyzed reaction should proceed through an open TS and the (3-polar effect described on p. 96 prevails, resulting in the anti-3,5-isomer. 

The effect of the steric bulk of the hydride reducing agent has been examined in the case of 3-benzyloxy-2-butanone.135 The ratio of chelation-controlled product increased with the steric bulk of the reductant. This is presumably due to amplification of the steric effect of the methyl group in the chelated TS as the reductant becomes more sterically demanding. In these reactions, the degree of chelation control was also enhanced by use of CH2C12 as a cosolvent. 

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

Oxy substituents can also lead to chelation control. Excellent stereoselectivity is... 

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. 

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. 

Further variations of the Claisen rearrangement protocol were also utilized for the synthesis of allenic amino acid derivatives. Whereas the Ireland-Claisen rearrangement led to unsatisfactory results [133b], a number of variously substituted a-allenic a-amino acids were prepared by Kazmaier [135] by chelate-controlled Claisen rearrangement of ester enolates (Scheme 18.47). For example, deprotonation of the propargylic ester 147 with 2 equiv. of lithium diisopropylamide and transmetallation with zinc chloride furnished the chelate complex 148, which underwent a highly syn-stereoselective rearrangement to the amino acid derivative 149. 

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