Remote nucleophile addition

The organochromium complex 47 provides a good example of remote addition to an j " complex (Scheme 14.18) with stereocontrolled reaction with the nucleophile and trapping the anion [198]. Similar examples have been reported by Uemura s group [199], establishing the general principles of remote nucleophile addition to tf Cr(CO)3 complexes. An example from Muller in Munich has used this effect to add PrS" to an allenylbenzene ligand [200]. 

Remote Nucleophile Addition in Synthetic Applications of Multihapto-Complexes... 

With chiral auxiliaries1,41 a remote chiral moiety is temporarily introduced into the substrate in order to direct the nucleophilic addition diastereoselectively. The chiral auxiliary can be removed from the initial addition product with complete conservation of the chirality of the desired product and also of the chiral auxiliary. The recovered chiral auxiliary can then be reused in further reactions. Therefore, chiral auxiliaries are used to chiralize an a priori achiral carbonyl substrate by the introduction of a covalently bound, but nevertheless easily removable, chiral source. 

Remote steric effects have also been noted to play an unanticipated role in the sense of asymmetric induction. This is apparent from related condensations carried out on aldehydes 106 (26) and 107 (eqs. [76]-[78]) (26,92). Other examples illustrating the influence of remote structural perturbations on the carbonyl addition process have been observed in these laboratories. The addition of the lithio benzoxazole 110 to aldehyde 108 proceeded with good Cram diastereoface selection (95a), whereas the same nucleophilic addition to aldehyde 109 was stereorandom (95b). 

With metals in place of carbons, we might expect some similarities as well as differences, the latter due to the closer packing of energy levels and the availability of nonbonding (or nearly so) orbitals centered on the metals. One major difference between MeM bonds and CeC bonds is especially evident in nucleophilic addition. In eq. 4, displacement of the tr-bond by a nucleophile renders the remote carbon nucleophilic as a result of its nonbonding lone pair. However, displacement of the -bonds of MhM apparently renders the remote metal electrophilic as seen by electron counting arguments (eq. 5). Assume that both M and M1 have... 

Wu, Y.-D. Tucker, J. A. Houk, K. N. Stereoselectivities of nucleophilic additions to cyclohexanones substituted by polar groups. Experimental investigation of reductions of trans-decalones and theoretical studies of cyclohexanone reductions. The influence of remote electrostatic effects, J. Am. Chem. Soc. 1991,113, 5018-5027. 

Stereoselective, conjngate allylation of more remote positions nsing aUyl trimethylsilane and TiCU is possible. Further transformation by nucleophilic addition and ringclosing metathesis affords fused polycychc ring systems (Scheme 88). Stabilized anions and organocopper see Copper OrganometaUic Chemistry) reagents also participate in Michael-type additions to complexed Q, /3-unsaturated aromatic enones. 

In general, nucleophilic addition reactions using Grignard or organolithium reagents to -chiral or other remotely chiral ketones usually yield mixtures of stereoisomers which are not synthetically use-fiil.9,12-27 However, some specific examples of stereoselective organolithium and Grignard additions to these remotely chiral carbonyl compounds have been reported. 

Nucleophilic additions to cyclic carbonyl compounds differ greatly from those of acyclic systems. In acyclic systems, only the configuration at an adjacent (1,2-asymmetric induction) or nea y center (remote asymmetric induction) is usually considered in predicting the outcome of nucleophilic attack. In cyclic systems, the conformation of the entire molecule (which is in part determined by the individual substituents) must be considered when predicting the mode of nucleophilic attack. Furthermore, a number of other factors such as torsional and electronic effects also play a role in the stereochemical course of additions to cyclic substrates. The relative importance of all of these effects (as well as others) has been the subject of considerable debate in the literature, and has not as yet been adequately resolved. ... 

Nucleophilic addition of alkyl lithium to difluorovinyl-substituted epoxide (48) proceeds on the difluoromethylene carbon via the addition-ring opening pathway [16]. However, trimethylaluminum reagent transfers the methyl group at the carbon remote from the difluorinated carbon of 50 presumably via the Lewis acid catalyzed ring opening-addition mechanism as shown in Scheme 2.26. 

Nucleophilic addition to organic radical-cations is one of the most common pathways to produce radicals. Irradiation of a wide variety of A-(2-alkenyl)- and N-(3-alkenyl)phthalimides and A-alkenylphthalimides [26] with a remote alkenyl double bond [27] afford new 5-, 6- and medium-size ring systems. Irradiation in methanol-acetonitrile triggers intramolecular electron transfer from the olefin double bond to the excited phthalimide carbonyl group. Because of the highly nucleophilic character of methanol, the olefin radical-cation can be trapped. The derived radical combines with the radical-anion to yield coupling products (Scheme 15). 

Although there are some mechanistic uncertainties, there is evidence that the reaction occurs via two successively formed arynes produced after metal-halogen exchange at both iodines. If arynes were formed independently at each halogen pair, one would expect a mixture of m- and p-terphenyls as products. It is thought that the regioselectivity in the nucleophilic additions to aryne intermediates 638 and 639 is a consequence of the need to keep the two carbanionic sites on the benzene ring remote (i.e. para) to each other. 

The pattern of chemical reactions observed for these compounds clearly sets them apart from "Fischer-type" carbyne complexes of GroupVI e.g., W(hCR)X(CO)4. Whereas the "Fischer-type" complexes typically react with nucleophiles at the carbyne carbon all of the reactions observed for the five coordinate mthenium and osmium complexes, including the cationic examples, are electrophilic additions to the MsC bond. The following sections deal individually with, protonation, addition of halides of the coinage metals, addition of chlorine and chalcogens, and finally an attempted nucleophilic addition where the nucleophile is directed to a remote site on the aryl ring of the carbyne substituent. 

The Pd(ll)- and Pt(ll)-promoted nucleophilic additions to olefins are important reactions in organic synthesis. Nucleophiles that have been shown to add to coordinated olefins include OH , RO , AcO , CP, amines, and amides, and with the possible exception of OH", nucleophilic attack takes place on the side of the double bond remote from the metal. The main difference between Pd(ll)- or Pt(Il)-promoted and Fe(II)-promoted addition is that nucleophilic attack on Pd(ll)- or Pt(II)-coordinated monoolefins results in reduction of the divalent metal to the zero valent state. In most cases, Pd(ll) salts promote nucleophilic attack on olefins more readily than Pt(II) salts (Hartley, 1973 Maitlis, 1971). Equations (97) (Stern and Spector, 1961), (98) (Baird, 1966), (99) (Kitching et al., 1966), (100) (Akermark et al., 1974), and (101) (Kohl and Van Helden, 1968 Henry, 1972) illustrate some typical Pd(ll)- and Pt(II)-promoted additions to olefins. 

Linear Alkenes and Alkynes.— Nucleophilic addition to co-ordinated alkenes can either occur on the same side as the metal (cm attack) or on the side remote from the metal (trans attack) (Scheme 3). A study on the oxidative hydrolysis of alkenes in the... 

The examples of nucleophilic substitution discussed in Sect. 3.4 belong to the ipso-type [185]. In c/ne-substitution, the leaving group departs from the position adjacent to the nucleophile addition site, and in teZe-substitution, the leaving group departs from a more remote position on the ring or even from a side-chain [159]. cine- and feZe-substitutions of various nonaromatic, aromatic and heteroaromatic compounds, including thiophene, have been reviewed [185]. 

For olefins with Ji-substitucnts, whether electron-withdrawing or electron-donating, both the HOMO and LUMO have the higher coefficient 021 the carbon atom remote from the substituent. A predominance of tail addition is expected as a consequence. However, for non-conjugated substituents, or those with lone pairs (e.g. the halo-olefins), the HOMO and LUMO are polarized in opposite directions. This may result in head addition being preferred in the case of a nucleophilic radical interacting with such an olefin. Thus, the data for attack of alkyl and fluoroalkyl radicals on the fluoro-olefins (Table 1.2) have been rationalized in terms of FMO theory.16 Where the radical and olefin both have near neutral philicity, the situation is less clear.21... 

The effect of remote halo substitution on the face selectivity of addition to 5-haloadamantan-2-ones (62b) has been extended to the corresponding nor- and homoadamantane systems, (62a) and (62c), and to some of their aza and diaza analogues. A syn approach of the nucleophile is favoured in all cases. 

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