Chelation, regioselective reaction

In the former reaction regioisomers are possibly formed, so regioselectivity cannot be controlled. Chelation-assisted reactions, on the other hand, occur regioselec-tively, usually at the position ortho to the directing group. 

The hydroxyalkylation of phenols with chiral glyoxylates, followed by hydrolysis, gives regioselectively 2-hydroxymandelic acids with high enantioselectivity (eqnation 28). The crystal-structure determination of the titanium phenoxide complex shows evidence for chelation-controlled reaction giving the observed high enantioselectivities . ... 

Finally, we invented a highly regioselective reaction promoting the cyclodehycfrative collapse of specifically dioxaphosphorane O that is presumably controlled by Li " ion chelation (52). When LiBr was added to a DMF solution containing l,3,2X5-dioxaphospholanes N and O, a facile decomposition (50°C) occurred, affording methyl allopyranoside 20 as the exclusive product (>99% by NMR). The rate constant for the uncatalyzed decomposition (in the absence of LiBr) is kuncat 1.5 X 10" s (65°C) while the catalyzed process has a rate constant, k / =... 

Optically active D- and L-Ins(1,3,4,5)P4 were also prepared from the orthoester 95 by Vasella et al. although the process required many additional steps compared with the synthesis of the racemic material described above. The orthoester 95 was regioselectively silylated to give 58% of 100 which was then mono-benzylated by the chelation-controlled reaction mentioned above to afford the ether 101 in 99% yield (Scheme 3-14). Chiral synthetic intermediates... 

Regioselective Reactions. An important attribute of DIBAL is its capacity to react regioselectively. Acetal cleavage is a classical example of this property, which finds its source in electronic, steric, and/or chelation effects. The reduction of aryl-1,2-ethanediol benzylidene acetals is controlled mainly by electronic effects a change in electron donating capacity of the aryl moiety changes the regioselectivity of the reaction (eq 43).4 ... 

Regioselective Reactions Based on Chelation and Participation of Heteroatoms... 

A synthetically useful diastereoselectivity (90% dc) was observed with the addition of methyl-magnesium bromide to a-epoxy aldehyde 25 in the presence of titanium(IV) chloride60. After treatment of the crude product with sodium hydride, the yy -epoxy alcohol 26 was obtained in 40% yield. The yyn-product corresponds to a chelation-controlled attack of 25 by the nucleophile. Isolation of compound 28, however, reveals that the addition reaction proceeds via a regioselective ring-opening of the epoxide, which affords the titanium-complexed chloro-hydrin 27. Chelation-controlled attack of 27 by the nucleophile leads to the -syn-diastereomer 28, which is converted to the epoxy alcohol 26 by treatment with sodium hydride. 

Microwave-assisted Heck reaction of (hetero)aryl bromides with N,N-dimethyl-2-[(2-phenylvinyl)oxy]ethanamine, using Herrmann s palladacycle as a precatalyst, yielded the corresponding /3-(hetero)arylated Heck products in a good EjZ selectivity (Scheme 79) [90]. The a/yd-regioselectivity can be explained by the chelation control in the insertion step. This selectivity is better than 10/90 when no severe steric hindrance is introduced in the (hetero)aryl bromides. The process does not require an inert atmosphere. There is evidence that a Pd(0)/Pd(II)- and not Pd(II)/Pd(IV)-based catalytic cycle is involved. Similarly, other j6-amino-substituted vinyl ethers such as... 

Several Pd11 complexes with thiolate or thioether derivative ligands have been studied to be applied in the hydroxycarbonylation reaction.394 Aminothiolate complexes of palladium with PPh3 catalyze the conversion of styrene to 2-phenylpropionic acid in high yield and excellent regioselectivity.644 Under mild conditions and in the presence of a catalytic amount of an S, TV-chelated palladium or//zo-amino-arenethiolate complex, styrene reacts with CO and oxalic acid or water to selectively give 2-phenylpropanic aid in high yield.645... 

Reduction of a. -epoxy esters to fi-hydroxy esters. Sml2 alone reduces these esters to a mixture of a- and p-hydroxy esters. The reaction rate and yield is increased by addition of HMPT. Addition of a chelating agent, TMEDA or N,N-dimethylaminoethanol (DMAE), results in regioselective reduction to p-hydroxy esters (equation I). The system reduces optically active epoxy esters with complete... 

The regioselectivity of Michael additions of thiolates to 2,4-dienones can be altered drastically by variation of the reaction conditions and addition of Lewis acids to the reaction mixture. Lawton and coworkers examined the reaction of 2-mercaptoethanol with l-(3-nitrophenyl)-2,4-pentadien-l-one and observed a high regioselectivity in favor of the 1,6-addition product at 45 °C (equation 42)123,124. Lowering of the reaction temperature caused an increase in the amount of 1,4-adduct, and at —40°C, a product ratio of 40 60 was found. These events suggest that kinetic control favors the 1,4-addition product whereas the 1,6-adduct is thermodynamically more stable. If, however, the reaction was carried out with a complex of the dienone and titanium tetrachloride, only the 1,4-adduct was isolated after hydrolytic workup123. Obviously, this product is trapped as a metal chelate which prevents formation of the 1,6-adduct by retro-Michael/Michael addition. In the absence of the chelating Lewis acid, the 1,4-addition product can indeed be converted... 

An X-ray crystal structure analysis was obtained from the 3-(trimethylsilyl)-aUyllithium-(—)-sparteine complex (5 )-302b. It reveals the monomeric structure of these aUyllithium compounds and a -coordination of the ally lie anion to the lithium cation. The latter is tetracoordinated and takes advantage of the chelating 0x0 group. The fixation of the lithium at the a-carbon atom is supposed to be the origin of the high regioselectivity of several substitution reactions. 

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