Nucleophilic displacement stereochemistry

The smooth intramolecular nucleophilic displacement of biphenyl carboxylic acids leading to benzocoumarins (See Section II.A.) inspired also investigation of the behavior of similar diphenyl ether, diphenyl sulfide and A-methyldiphenyl amine derivatives 458 under similar conditions. However, all these attempts to achieve cyclization to tricyclic compounds 459 were unsuccessful, probably due to the unfavorable stereochemistry for the formation of the required seven-mem-bered transition states and also to the presence of the deactivating bridge groups X (Eq. 42) [68JCS(C)1030]. 

Michalski, M., Mikolajczyk, M., and Omelanczuk, ]., Stereochemistry of nucleophilic displacement reaction at thiophosphoryl centre. An example of the Walden cycle involving phosphorus, Tetrahedron Lett., 1779, 1965. 

Reactions.—Alkaline Hydrolysis. The first total resolution of a heterocyclic phosphonium salt containing an asymmetric phosphorus atom (128) has been reported, providing ready access to optically active phospholan derivatives of value for studies of the stereochemistry of nucleophilic displacement at phosphorus.124 Alkaline hydrolysis of (128) proceeds with retention of configuration at phosphorus to form the oxide (129). Stereochemical studies in the phospholan series have also been facilitated by the X-ray investigation125 of an isomer of l-iodomethyl-l-phenyl-3-methylphospholanium iodide, which is shown to have the structure (130). 

The most frequently encountered reactions in organic sulfur chemistry are nucleophilic displacement reactions. The mechanism and steric course of reactions have been the main points of interest of research groups all over the world, in particular, Andersen, Cram, Johnson, and Mislow in the United States Kobayashi and Oae in Japan Kjaer in Denmark and Fava and Montanari in Italy. The results of these investigators have been discussed exhaustively in many reviews on sulfur stereochemistry. In a recent report on nucleophilic substitution at tricoordinate sulfur, the literature was covered by Tillett (10) to the end of 1975. Therefore only some representative examples of nucleophilic substitution reactions at chiral sulfur are discussed here. However, recent results obtained in the authors laboratory are included. 

Contrary to the case of anionic reactions, the formation of a strong proton-bound dimer for alcohols suggests that nucleophilic displacement may actually involve a frontside attack. Recent experiments carried out at atmospheric pressure by Speranza and Angelini (1980) using radiolytic techniques with isolation and glc analysis of neutral products reveal some interesting stereochemistry. For example, the reaction of protonated epoxy-rra/is-but-2-ene with H20 results in 98% inversion of configuration, while a similar reaction with cis-1 -chloro-4-methylcyclohexane results in approximately 80% of tro/is-4-methylcyclohexanol. With the high pressures utilized and with the possible participation of cluster ions a likelihood in this case, the data are consistent with a Walden inversion for these cases. 

Nucleophilic displacement on 1-chlorosilacyclopentanes is dominated by inversion, in contrast to silacyclobutanes (78JOM(154)203). For 2-oxa- and 2-thia-silacyclopentanes, however, both inversion and retention are observed. The stereochemistry is determined by the leaving group and the electronic nature of the nucleophile rather than ring strain... 

Oxidative Addition of Alkyl Halides to Palladium(0). The stereochemistry of the oxidative addition (31) of alkyl halides to the transition metals of group VIII can provide information as to which of the many possible mechanisms are operative. The addition of alkyl halides to d8-iridium complexes has been reported to proceed with retention (32), inversion (33), and racemization (34, 35) via a free radical mechanism at the asymmetric carbon center. The kinetics of this reaction are consistent with nucleophilic displacement by iridium on carbon (36). Oxi-... 

NUCLEOPHILIC DISPLACEMENT AT SILICON CONTROLLING FACTORS OF THE STEREOCHEMISTRY... 

It should be noted that pseudorotation does not explain the retention as stereochemistry in nucleophilic displacements it only yields a picture of observed stereochemical events. Retention is the consequence of a nucleophilic attack at 90° with respect to the leaving group. 

NUCLEOPHILIC DISPLACEMENTS AT SILICON A RATIONALIZATION OF THE STEREOCHEMISTRY BY A FRONTIER-ORBITAL APPROXIMATION... 

Cryptand Effect on the Stereochemistry and Rate of Nucleophilic Displacements at Silicon... 

Studies in the stereochemistry of nucleophilic displacements at silicon over the past few years have been numerous. Significant progress has been achieved in establishing the controlling factors of the stereochemistry (i) the lability of the leaving group, (ii) the electronic character of the nucleophile, and (iii) the bond angles at silicon. 

Stereochemistry is one of the most important characteristics of a reaction mechanism. In the nucleophilic displacement of iodide ion on. V luilyl bromide, Eq. (2). the reaction is known to occur with inversion. If one... 

The mechanisms of nucleophilic displacements on tricoordinated sulfur are not yet fully understood. The stereochemistry can be determined by studying the relative configuration of starting materials and products.63 The substituents attached to tricoordinated sulfur form a tetrahedron with the lone pair occupying one of the apices (10) but, unlike its nitrogen-containing analog, the sulfur... 

Carrying out the benzhydrylpiperazine formation via nucleophilic displacement as depicted in Scheme 2 using the enantiopure (—)-(2R,5S)-l -allyl-2,5-dimethylpiperazine provides two stereoisomers, epimeric at the benz-hydryl position. These epimers are separable by common chromatographic techniques (although these are sometimes difficult separations), and the absolute stereochemistry of the products has been proven via x-ray crystallography [19,23,40,41]. For large-scale preparation, a stereoselective approach to the final products is preferred to minimize waste and reduce costs. Two distinct stereoselective routes to benzhydrylpiperazines have been described. 

K. Mislow, Role of Pseudorotation in the Stereochemistry of Nucleophilic Displacement Reactions, Acc. Chem. Res. 1, 321 (1970). 

Having established the three-dimentional structure of carbocations as planar, we can now study the stereochemical progression of Sk 1 reactions as compared to Sk2 reactions. As shown in Scheme 5.6, the stereochemical course of an Sk2 reaction is well defined because nucleophilic displacement of a leaving group proceeds with inversion of stereochemistry. Thus, the stereochemical outcome is defined by the stereochemistry of the starting material. As for SnI reactions, since the step required for initiation of these reactions involves formation of a planar species, incoming nucleophiles have equal access to both sides of the reactive carbocation. As shown in Scheme 5.7, this results in complete elimination of... 

He and his students developed C-alkylation with quaternary ammonium salts and nucleophilic displacements on such salts, including the stereochemistry. His name is immediately associated with important innovations in the use of polyphosphoric acid for inter- and intramolecular condensations, cyclizations, and functional conversions in organic chemistry. He pioneered the use of boron trifluoride as an efficient catalyst in the Fischer indole synthesis and discovered new reactions of anils, including Diels-Alder reactions. He and his students delineated the requirements for disproportionation of tertiary amines. He developed the synthesis and chemistry of arylboranic acids. One of his fundamental ideas was for the incorporation of sufficient boron into organ-specific drugs that they could then be... 

Preparation. [(i )-a-(2-Naphthyl)aminomethyl]ferrocene was prepared in three steps from ferrocenyl 2-naphthyl ketone featuring an asymmetric CBS reduction with >99% ee (eq 1). After protection of the secondary hydroxyl group with an acetyl group, a nucleophilic displacement of the acetoxy group with an amino group proceeded with retention of stereochemistry. A range of different variations of [(i )-a-(2-naphthyl)aminomethyl]ferro-cene could be prepared using this sequence with similar efficiency. 

Sn2 reaction. This problem together with the associated stereochemical ambiguity was described in Chapter 23. In contrast, jt-aUyl cation complexes of palladium allow both the stereochemistry and regiochemistry of nucleophilic displacement reactions to be controlled. 

R. J P. Corriu, C. Guerin, Nucleophilic Displacement at Silicon. Stereochemistry and Mechanistic Implications", J. Organomet. Chem. 1980,198, 231. 

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