Chelation-controlled product

In the case of the amide 11 (R = CI13) derived from 2-oxopropanoic amid and amine G the chelation-controlled product is predominantly formed with all organometallic reagents. No reversal of the stereochemistry is observed, presumably for the same steric reason as with the corresponding pyruvic amides derived from amines E and F. 

The reaction between a-alkoxyaldehydes and allylsilanes is highly stereoselective in favor of chelation-controlled products if tin(IV) chloride is used as the Lewis acid, whereas boron trifluoride gives modest stereoselectivity in favor of the nonchelation-controlled product58. 

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. 

Chelation-controlled product is formed from reaction of a-benzyloxypropanal and the TBDMS silyl ketene acetal derived from ethyl acetate using 3% LiC104 as catalyst.94... 

An indication of the relative effectiveness of oxygen substituent in promoting chelation of lithium enolates is found in the enolates 3a-d. The order of preference for the chelation-controlled product is CH30CH20 > TMSO > PhCH20 > TBDMSO, with the nonchelation product favored for TBDMSO.107... 

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. 

RCu-MXn, but Alexakis and coworkers163-179 showed that the chelate-controlled product (127) was obtained regiospecifically with lithium organocuprates, RaCuLi (equation 48). 

Grignard reagents also add diastereoselectively to oc-chiral, oc-oxygenated aldehydes and ketones. The chelation-controlled product constitutes the major product (Figure 10.41). It is the diastereomer that is produced via the Cram chelate transition state of Figure 10.16... 

A sterically less hindered N atom is found, for example, in the a-aminated a-chiral aldehyde B in Figure 10.42. This is because this amine is secondary and bears only two nonhydrogen substituents. The N atom of aldehyde B is so unhindered that it can be bound firmly in a chelate by the magnesium. Consequently, the addition of a Grignard reagent to aldehyde B exclusively affords the chelation-controlled product. 

In contrast, the diastereoselectivities of Figure 8.10 can be observed for many additions of hydride donors to carbonyl compounds which contain a stereocenter in the a position with an O or N atom bound to it. One of the product diastereomers and the relative configuration of its stereocenters is called the Felkin-Anh product. The other diastereomer and its stereochemistry are referred to as the so-called Cram chelate product. If the latter is produced preferentially, one also talks about the occurrence of chelation control or—only in laboratory jargon—of the predominance of the chelation-controlled product. ... 

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... 

In the reaction of a-alkoxyaldehydes the stereochemical outcome is different— reactions in the pericyclic mode now lead preferentially to the 5,6-anti product. The reaction of chiral a-benzyloxyaldehyde 6 under the influence of MgBr2 afforded a single pyrone 7, which was consistent with a chelation-control product [9b,12]. A chelated complex was formed, and the exo transition state III was preferred because of steric repulsion between the diene and the chelated ring (Sch. 4). 

Simple addition of n-decylmagnesium bromide to (7) yields an approximately equal ratio of products (8) and (9). The use of conditions which promote chelation (excess Grignard reagent) produces a shift in the pnxiuct ratio (63 37). Addition of ZnBr2 to the reaction mixture further increases the amount of chelation-controlled product formed (85 15 Table 4). 

Nucleophilic additions to tetrahydrofurfural (10 equation 6) proceed under similar constraints. Grignard additions in the presence of HMPT favor formation of product (11), arising from Felkin-Anh addition (Table 5). In the absence of HMPT, nucleophilic addition yields the cyclic chelation control product (12) as the major isomer. ... 

A high level of 1,3-asymmetric induction was achieved by the assistance of a Lewis acid. Complexa-tion of a 3-alkoxy aldehyde with TiCU followed by addition of Bu2Zn, allylsilane or silyl enol ethers at -78 C results in chelation-controlled products in >85% selectivities (Scheme 12). Even a considerable level of 1,4-asymmetric induction is observed with the Me2Zn-TiCl4 system (equation 33). ... 

Lithium aluminum hydride also gave the chelation-controlled product with methyl 2-benzoyl-propanoate, but with a d.r. synjami) of only 90 103°. 

Finally, the reduction of an elaborate substrate to give the chelation-controlled product 6 serves to illustrate that, in the right circumstances, stereocontrolled reduction of an acyclic ketone can be applied efficiently at a late stage in a complex synthesis55. 

Aldehyde 50 is an excellent chiral intermediate in reactions with organometallics. Addition at —78 °C of vinylmagnesium bromide to 50, that has been precomplexed with magnesium bromide etherate, affords the chelation-controlled product 51 with remarkably high diaster-eofacial selectivity (155 1). It is imperative that methylene chloride be used as the solvent in order to achieve this level of selectivity. In fact, if commercial vinylmagnesium bromide in THF is to be employed, the THF must be removed and replaced with methylene chloride [13] or else selectivity drops to 40 1. An analogous reaction of 50 with allyl tri- -butylstannane at — 23 °C furnishes chelation-controlled product 52 with 49 1 stereoselectivity. 

A variety of Lewis acids have been used to promote the addition of an allylsilane or allylstannane to an aldehyde (or ketone or imine). The Lewis acid BF3-OEt2 is effective and promotes Cram (Felkin-Anh)-type addition (see Section 1.1.5.1). However, Lewis acids such as TiCU, SnCU or MgBr2 can co-ordinate to a neighbouring (normally a-) heteroatom and promote chelation-controlled addition. For example, allylation of the aldehyde 161 gave either the Cram-type product or the chelation-controlled product depending upon the nature of the Lewis acid (1.153). 

When 16 was treated with the carbanion of 21 in a mixture of ether-hexane (1 1), the coupling proceeded smoothly to give the expected product in excellent yield, which was converted to the ketone in the usual way. Reduction with sodium borohydride gave only the non-chelation-controlled product (26), which was easily converted to 27. The usual conversion of 27 gave the aldehyde (segment B/C 28). 

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