Intramolecular chelation

Lindo-rv.ff oselecli ve oxacydization of polyepoxides is less common the first ster-eospedfic tandem endo-regioselective biomimetic oxacydization of polyepoxides to fused THP rings has only recently been reported [38a], The cyclization of the hydroxy-methoxymethyl-substituted triepoxide 75 (a 1,4,7-triepoxide), promoted and directed by La(OTf)3 through an intramolecular chelation and based on a procedure originally described for a monoepoxide system [38b], afforded the tri-... 

An unexpected result was obtained in the coupling of bis(3-alkoxypropyl)zincs with 152 [56] (Scheme 25). A substantial erosion in 1,3-anti selectivity was observed. The lower diastereoselectivity observed in these couplings may be a consequence of an equilibrium between the open-chain form (167) and the intramolecular chelated form (168) of the dialkylzinc, which increases the steric bulk about the C-Zn bond [57,58] (Fig. 6). As the steric bulk of the chelated form increases, addition from the less hindered equatorial trajectory begins to become competitive, and substantial amounts of the 5yn-l,3-diol synthon are generated. 

The same coordination is used to account for the observed anti preference in the allylation of (t-hydroxybutanal with allyl bromide/indium in water (Scheme 8.16). The intermediate leads to the anti product. In support of the intramolecular chelation model, it is found that if the hydroxy group is converted to the corresponding benzyl or t-butyldimethylsilyl ether, the reaction is not stereoselective at all and gives nearly equal amounts of syn and anti products. 

The Zn11 cation may lend soft electrophilic assistance for transmetalation. The most efficient such assistance is in the intramolecular chelating mode, which is exemplified by cross-coupling of... 

The carbocupration of methoxyallene affords a (Z)- or (E)-enol ether depending on the solvent used [52], In THF, the reaction exhibits Z-selectivity because the coordination ability of THF excludes the intramolecular chelation effect of the methoxy group, which may be responsible for the E-selectivity for the reaction in ether (Scheme 10.49). 

Fig. 4 Halotelluronium species stabilized by intramolecular chelation formed by oxidative addition of halogens to A,A-dimethyl-2-(aminomethyl)phenyl phenyltelluride (17).

Reaction of the intramolecular chelating copper afkoxides 121 or 122 with (Me3Si)3 CZnCl afforded complexes 123 and 124 (equation 22) . In these complexes the copper bis(alkoxide) moiety acts as an 0,0-chelating ligand coordinated to zinc. 

Carbocupration of chiral alkynylsulfoxides 47 in a regio- and stereospecific manner produces alkenyl organocopper 48, which is subsequently reacted with bis(iodomethyl) zinc in the presence of aldehydes or imines. The zinc carbenoid homologation step leads to 49, the conformation of which is controlled by intramolecular chelation 49 reacts with the aldehyde or imine before it can undergo a -elimination (cf. equation 20). The final product 63 is generally obtained with high diastereoselectivity and in good overall yield (Table 8). 

The intramolecular chelation between the ether oxygen and the zinc atom shown in equation 34 can be utilized to create stereocontrol as demonstrated in equation 3 545. 

For unsubstituted allylic systems some kind of intramolecular chelation is necessary to obtain diastereoselection. If the ethylene moiety in 87 is replaced by an ethyl group, diastereoselectivity is lost completely (72% yield, dr = 50/50). The syn isomer of 88 can be obtained if the methyl substituent is not attached to the vinyl but to the allyl moiety (equation 40), taking advantage of the selectivity arising from a crotyl system (cf. Scheme 6). 

If the facial selectivity created by intramolecular chelation is combined with the selectivity arising from substitution at the allylic system, the relative stereochemistry of three stereogenic centres can be controlled (equation 41 )49. 

Dimetallic reagents of the vinylidene type (Section II.A.2), in which the reactivity of one metal is lowered by intramolecular chelation, can be selectively chlorinated to... 

Kspecially interesting is the fact that the epoxide ring is activated by intramolecular chelation" <37). Pnor to this discovery, 18 standard reagents had tailed in opening the epoxide.7 The reducing agent attacks activated epoxide 37 selectively from the sterically more accessible side and produces a tertiary alcohol Selective protection of the secondary alcohol leads to compound 16... 

Analogous intramolecular chelation-controlled ketone/olefin couplings with Sml2, in which Sm+3 was complexed in a cyclic manner to the ketyl anion and a /1-carbonyl of an ester or amide functionalilty, were reported as early as 1987 (Scheme 31)86. The cyclized samarium intermediate 49 could be further reacted with added electrophiles such... 

A series of complexes (Chart 5) have been reported that comprise both a poly(pyrazolyl)borate ligand and an intramolecularly chelating, monoanionic coligand. These are typically obtained via halide displacement and dimer cleavage by the respective sodium or potassium poly(pyrazo-lyl)borate salt, a means by which 462—466,45 467—469,143 and 470 479144 145 were each prepared in good yield, while the related poly (pyrazolyl)methane complexes 480+— 483+ were isolated as their perchlorate salts in the presence of NaClO 145... 

They found that the normal stereochemical tendency can be overcome by specific intramolecular chelation effects ... 

Instead of solvent complexation, intramolecular chelation can also stabilize germanium-centered anions. Aryl(8-methoxy-l-naphthyl)hydrogermyllithiums, prepared from the corresponding chelated organogermane in 50-90% yield, are stable and their spectroscopic characteristics suggest a double-metal complexed structure (equation 7)17. 

To assess the effect of intramolecular chelation in this class of organolithium, Gawley also made 157 and treated it under similar conditions.57 In THF alone, the MEM-protected 158 has greater chemical stability than 155, and is configurationally stable up to about -60 °C. Like the lithiated Boc-pyrrolidine 138 (but unlike the lithiated /V-methyl pyrrolidines 155) TMEDA tends to decrease its configurational stability and a direct comparison between MEM protected 158 and 155 in the presence of TMEDA shows that the MEM group also... 

When hydroxy bromide 20 is subjected to the typical coupling conditions, neither 3- nor 2-PyCHO shows high diastereoselectivity (Scheme 25). The low-level stereochemical bias toward 3-PyCHO can be accounted for in terms of the Felkin-Anh transition states 21. When 2-PyCHO is involved, the intramolecular chelation option 22 is favored over 23, despite the obvious steric congestion associated with the onset of intermolecular chelation in both transition states. 

Thioxoketones with aromatic -substituents show an equilibrium mixture of 4 1 of the enol enethiol conformers150. Structures of some five and six-membered 2-acylcyc-loalkanethiones and 2-thioacylcycloalkanones have been shown by H NMR, IR and UV spectroscopy also to exist as equilibrium mixtures of the enol and enethiols which interconvert very rapidly by intramolecular chelate proton transfer151. ... 

Zinc chloride has also been observed to have a significant influence on the enantiose-lectivity of these reactions. But several other important parameters have been pointed out, such as the temperature (best performances are obtained at very low temperatures), the solvent (HMPA is often required) or the concentration of the lithium amide96. As underlined above about the stereoselectivity of the deprotonation, the formation of lithium amides-lithium chloride mixed aggregates (1 1 or 2 1) has been proposed to rationalize the important salt effects (Scheme 20), the amide homogeneous dimer being supposed to provide only mediocre enantioselections. With diamines, the intramolecular chelation would provide a fairly rigid system. 

The relative stereocontrol of carbons 1, 2 and 6 observed in the above example has been assigned to the intramolecular chelation of the lithium of the intermediate enolate by the carbonyl of the second ester group. Note that lithium amide cuprate reagents also add efficiently to enoates and dienoates163. 

---