Regioselectivity complexes

Optically active (—)-(8R)-methylcanadine was stereoselectively synthesized through selective monocomplexation of (—)-canadine (26) to chromium tricarbonyl (240). Heating of chromium hexacarbonyl with 26 effected regioselective complexation of the D ring to give the diastereomeric complexes, which were treated with n-butyllithium and trimethylsilyl chloride to give the 11-trimethylsilyl derivative 475 (Scheme 97). Methylation of this complex with methyl iodide gave stereoselectively the 8-methyl derivative 476 by preferential alkylation from the opposite face to the bulky chromium... 

Even more interesting is the observed regioselectivity of 37 its reaction with 2, 3 -cCMP and 2, 3 -cUMP resulted in formation of more than 90% of 2 -phosphate (3 -OH) isomer. The postulated mechanisms for 37 consists of a double Lewis-acid activation, while the metal-bound hydroxide and water act as nucleophilic catalyst and general acid, respectively (see 39). The substrate-ligand interaction probably favors only one of the depicted substrate orientations, which may be responsible for the observed regioselectivity. Complex 38 may operate in a similar way but with single Lewis-acid activation, which would explain the lower bimetallic cooperativity and the lack of regioselectivity. Both proposed mechanisms show similarities to that of the native phospho-monoesterases (37 protein phosphatase 1 and fructose 1,6-diphosphatase, 38 purple acid phosphatase). 

The propargylic cations [Co2(/i,i/2,Tj3-RC2CR2)(CO)6]+ react as electrophiles with a variety of heteroatom- and carbon-centered nucleophiles to provide, following demetalation, propargylated products with complete regioselectivity. Complexation of the triple bond circumvents isomerization to allenic products. Reaction with asymmetrical ketones results in attack by the cation exclusively (>95%) at the more substituted a-carbon.72,74 (See Scheme 11.)... 

Diederich and co-workers have synthesized a triscluster complex 47 of the unusual Cjg molecule via oxidative cyclotrimerization of the hexatriyne complex 48 (Scheme 4-17) [72]. The cyclocoupling efficiency benefits from the bent geometry of the coordinated triyne (a = 138°). Other noteworthy features include (1) the regioselective complexation of the silylated triyne (2) efficient desilylation of the complexed triyne. 

Benzyl ethers are commonly introduced by the conditions in category (a), section 2.3, Ethers, particularly when perbenzylation is required. The choice of conditions does not affect selectivity greatly (Figure 2.4) [9] except when the copper chelate method is employed. In the latter method dialkoxides (produced from diols with NaH) are deactivated by regioselective complexation of a copper salt so that the free alkoxide reacts preferentially Figure 2.5 illustrates a typical case [10] which should be compared with the variants in Figure 2.4. 

The regioselective complexation of D-mannitol, -galactitol, -xylitol, -ribitol and -erythritol with bis(phosphlne)platinum(II) carbonate complexes has been studied, and conformational analyses of the products by H n.m.r have been performed. Also a study on the preferred conformations of hex-l,S-dien-3,4-diols, which includes reference to hydroxylation reactions, suggesting an approach to hexitol and higher alditol syntheses has been reported. ... 

Hydrothiolation of Conjugated C-C Double Bonds. This reaction reported by He was best catalyzed by Ph3PAuBF4 in most cases and showed excellent regioselectivity. Complex 1 was shown in one case as an effective catalyst (eq 17). 

Resolution of o and m-substituted benzylalcohol chromium tricarbonyls by reduction of the corresponding aldehydes using bakers yeast has been achieved. The regioselective complexation of 1,2 9,10-dibenzo[2.2]paracyclophane-1,9-diene with Cr(CX))3 has been described. The diasteteoselective nuclec hilic 1,2-addition reactions of N-benzylidene-1--methylaniline chromium tricarbonyl has been achieved. A range of hetetobimetallic complexes of substituted mesitylene chromium iricarbonyls has been prepared. ... 

These data from ergosterol and ergosterol-type compounds prove very clearly that approach control in iron-complex formation differs markedly from the one in Diels-Alder cycloadditions. While here all examples investigated so far call for an a-approach of the dienophile to form products like 8 with remarkable regioselectivity, complex formation does at least to some extent take place from the P-side of the molecule. 

It is certainly noteworthy that this highly regioselective complex directed endo-mode cyclization was shown to be absolutely independent of the electronic properties of the triple bond substituent This means that one can switch from electron poor to electron rich substituents by employing the Nicholas complex. 

Figure 3 Cd NMR spectra of the Cd(ll) complexes of five different piperazine-pyridine ligands measured in ethanol at -50 C. The signal of the uncomplexed Cd cation is marked by an asterisk. Reproduced with permission of VCH Verlagsgesellschaft from Ratilainen J, Airola K, Kolemainen E and Rissanen K (1997) Regioselective complexation of new multiple piperazine/pyridine ligands differentiation by Cd-NMR spectroscopy. Chemische Berichte/RecueinZO 1353-1359.

Ratilainen J, Airola K, Kolehmainen E and Rissanen K (1997) Regioselective complexation of new multiple piperazine/pyridine ligands differentiation by " Cd NMR spectroscopy. Chemische Berischte/Recueil 130 1353-1359. 

The regioselectivity benefits from the increased polarisation of the alkene moiety, reflected in the increased difference in the orbital coefficients on carbon 1 and 2. The increase in endo-exo selectivity is a result of an increased secondary orbital interaction that can be attributed to the increased orbital coefficient on the carbonyl carbon ". Also increased dipolar interactions, as a result of an increased polarisation, will contribute. Interestingly, Yamamoto has demonstrated that by usirg a very bulky catalyst the endo-pathway can be blocked and an excess of exo product can be obtained The increased di as tereo facial selectivity has been attributed to a more compact transition state for the catalysed reaction as a result of more efficient primary and secondary orbital interactions as well as conformational changes in the complexed dienophile" . Calculations show that, with the polarisation of the dienophile, the extent of asynchronicity in the activated complex increases . Some authors even report a zwitteriorric character of the activated complex of the Lewis-acid catalysed reaction " . Currently, Lewis-acid catalysis of Diels-Alder reactions is everyday practice in synthetic organic chemistry. 

We shall only be concerned here with those reactions, which have been used in constructions of the carbon skeletons of complex compounds with concomitant regioselective incorporation of the double bond. 1,2-Eliminations are discussed on p. 137ff. 

Many successful regioselective syntheses of heterocydes, however, are more complex than the examples given so far. They employ condensation of two different carbonyl or halide compounds with one nitrogen base or the condensation of an amino ketone with a second difunctional compound. Such reactions cannot be rationalized in a simple way, and the literature must be consulted. 

Allylic acetoxy groups can be substituted by amines in the presence of Pd(0) catalysts. At substituted cyclohexene derivatives the diastereoselectivity depends largely on the structure of the palladium catalyst. Polymer-bound palladium often leads to amination at the same face as the aoetoxy leaving group with regioselective attack at the sterically less hindered site of the intermediate ri -allyl complex (B.M. Trost, 1978). 

The same regioselective and stereospecific reactions are observed in decalin systems. The 3/3-formate 605 is converted into the a-oriented (j-allylpalladium complex 606, and the hydride transfer generates the fra .s-decalin 607, while the cis junction in 610 is generated from the 3tt-formate 608 by attack of the hydride from the /3-side (609). An active catalyst for the reaction is prepared by mixing Pd(OAc)2 and BU3P in a 1 I ratio with this catalyst the reaction proceeds at room temperature. The reaction proceeded in boiling dioxane when a catalyst prepared from Pd(OAc)2 and BujP in a 1 4 ratio was used[390]. 

The regioselective and stereospecific construction of C-20 stereochemistry is explained by the following mechanism. The Pd(0) species attacks the ( )-/3-carbonate 616 from the a-side by inversion to form the Tr-allylpalladium species 620, which has a stable syn structure[392]. Then concerted decarboxylation-hydride transfer as in 621 takes place from the a-side to give the unnatural configuration in 617. On the other hand, the Tr-allylpalladium complex 622... 

The regioselectivity of addition is consistent with the electron distribution in the complex Hydrogen is transferred with a pair of electrons to the carbon atom that can best support a positive charge namely the one that bears the methyl group... 

To date (ca 1996) many potentially usefiil sucrose derivatives have been synthesized. However, the economics and complexities of sucrochemical syntheses and the avadabiLity of cheaper substitutes have limited their acceptance hence, only a few of them are in commercial use. A change in the price and availability of petroleum feedstocks could reverse this trend. Additional impetus may come from regioselective, site-specific modifications of sucrose to produce derivatives to facilitate and improve the economics of sucrochemical syntheses. For example, the microbe yigwbacterium tumifaciens selectively oxidizes sucrose to a three-keto derivative, a precursor of alkylated sucroses for detergent use (50). Similarly, enzymes have been used for selective synthesis of specific sucrose derivatives (21). 

In view of the overall increased reactivity of furan compared with thiophene it would be anticipated that furan would be less regioselective in its reactions with electrophiles than thiophene. Possible reasons for the high regioselectivity of furan in electrophilic substitution reactions include complex formation between substrates and reagents and the ability of heteroatoms to assist in the stabilization of cationic intermediates (80CHE1195). 

The mechanistic complexity of hydroboration-oxidation stands in contrast to the simplicity with which these reactions aie caiiied out experimentally. Both the hydrobo-ration and oxidation steps are extremely rapid reactions and are performed at room temperature with conventional laboratory equipment. Ease of operation, along with the fact that hydroboration-oxidation leads to syn hydration of alkenes and occurs with a regioselectivity opposite to Maikovnikov s rule, makes this procedure one of great value to the synthetic chemist. 

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