Inversion of configuration at carbon

Inversion of configuration at carbon in hydrolysis of methyl iodide. 

Stereoelectronic control also plays a role in mechanistic stereoselectivity. One such case is the very fundamental 8 2 process which proceeds rigorously with inversion of configuration at carbon. Because of that intrinsic and predictable stereoselectivity, the C-C disconnective Sn2 displacement transform is very important even though it does not directly reduce the number of stereocenters, e.g. 153 => 154. 

By studying the NMR spectra of the products, Jensen and co-workers were able to establish that the alkylation of (the presumed) [Co (DMG)2py] in methanol by cyclohexene oxide and by various substituted cyclohexyl bromides and tosylates occurred primarily with inversion of configuration at carbon i.e., by an 8 2 mechanism. A small amount of a second isomer, which must have been formed by another minor pathway, was observed in one case (95). Both the alkylation of [Co (DMG)2py] by asymmetric epoxides 129, 142) and the reduction of epoxides to alcohols by cobalt cyanide complexes 105, 103) show preferential formation of one isomer. In addition, the ratio of ketone to alcohol obtained in the reaction of epoxides with [Co(CN)5H] increases with pH and this has been ascribed to differing reactions with the hydride (reduction to alcohol) and Co(I) (isomerization to ketone) 103) (see also Section VII,C). 

Nucleophilic displacement of halide ion from a saturated carbon atom by alkali-metal diphenylphosphide reagents occurs with inversion of configuration at carbon, as is found in normal Sn2 displacements.19 Thus menthyl chloride or bromide gives ... 

Alkyl tosylates and mesylates are cleaved on the action of KOj in DMSO and give rise to the corresponding alcohols. This reaction also proceeds with inversion of configuration at carbon atoms (Morkovnik and Okhlobystin 1979). Such process may be of importance in prostaglandin chemistry. 

The double inversion sequence provides unequivocal evidence that the nucleophilic displacements assisted by neighboring boron proceed with inversion of configuration at carbon. 

Substituted cyclopropane systems also undergo nucleophilic addition of suitable solvents (MeOH). For example, the photoinduced ET reaction of 1,2-dimethyl-3-phenylcyclopropane (112, R = Me) with p-dicyanobenzene formed a ring-opened ether by anti-Markovnikov addition. The reaction occurs with essentially complete inversion of configuration at carbon, suggesting a nucleophilic cleavage of a one-electron cyclopropane bond, generating 113. The retention of chirality confirms that the stereochemistry of the parent molecule is unperturbed in the radical cation 112 " ". 

Xlld does not involve the chiral center, so if the reaction takes place by this pathway, the migration of the alkyl group from sulfur to palladium (with the concomitant or subsequent loss of sulfur dioxide) must take place with inversion of configuration at carbon. Inversion of configuration at carbon has been observed in the reverse-type reaction, the sulfur dioxide insertion into a carbon-iron sigma bond (49). Nucleophilic displacement at carbon in compounds of type Xld is unusually difficult, so the reaction via the sulfite intermediate Xlld would appear to be more likely. Conversion of the tosylate of l-phenyl-2,2,2-trifluoroethanol to the corresponding chloride, a reaction which takes place in the presence of tetra- (n-butyl) ajnmonium chloride with inversion of configuration at carbon, requires 100°C for 24 hrs in dimethylsulfoxide. 

A similar reaction has been reported by Stille et al. (251) using chiral alkyl halide. This reaction proceeds with inversion of configuration at carbon. The configuration was established by the rotation of the carbonylated complex which was also prepared by oxidative addition of acyl halide. 

Section III, B, 1). Thus, in chloride-containing acetic acid, acetate is not complexed to Pd(II) and acetoxypalladation is trans displacement of Pd(II) occurs in an Sj,2 fashion. Chloride is in the coordination sphere as well as in solution and can thus replace Pd(II) with either retention or inversion of configuration at carbon. 

On the other hand, t/ireo-Fe(f7 -C5H5)(CHDCHDCMe3)(CO)2 reacts with sulfur dioxide with > 95% inversion of configuration at carbon. Thus, sulfur dioxide insertion into the iron-carbon bond proceeds differently from carbon monoxide insertion, which is characterized by retention of configuration at carbon" . 

It has been shown that oxiranes can replace 1,2-dihaloalkanes in the synthesis of phosphiranes, provided that appropriate anionic RP reagents are used. The first example was described by Yoshifuji et al. (Equation (54)) <85CL44l>. Subsequently, it has been shown by Marinetti et al. that the so-called phospha-Wittig reagents transform oxiranes into phosphiranes with an inversion of configuration at carbon (Scheme 19) <92Sl57,93OM1207). Decomplexation by 1,2-bis(diphenylphos-phino)ethane is easily achieved in the molybdenum series. Optically active phosphiranes are readily accessible by this route. 

This reaction has been extended to a considerable number of monophenylcyclopropanes with low oxidation potentials < 1.4 V), other electron acceptors and nucleophiles (water, cyanide, ethanol, isopropyl alcohol, tert-butyl alcohol). anti-Markovnikov products analogous to 6 are generally formed as the main product however, frequently in moderate to low isolated yields.The nucleophilic substitution step [e.g. 4(4-) - 7] occurs for all mentioned nucleophiles with > 99% inversion of configuration at carbon and the rate is remarkably insensitive... 

All Sj 2 reactions occur with inversion of configuration at carbon. 

---