Stereochemistry backside attack

Stereochemistry Backside attack of the nucleophile (7.110) Trigonal planar carbocation intermediate (7.130)... 

Stereochemistry backside attack of the trigonal planar carbocation... 

If the addition of Br to the alkene results in a bromonium ion, the anti stereochemistry can be readily eiqilained. Nucleophilic ring opening by bromide ion would occur by backside attack at carbon, with rupture of one of the C—Br bonds, giving overall anti addition. 

Independent evidence for backside attack in gas-phase acid-induced nucleophilic substitutions was provided by a number of studies, carried out using stationary radiolysis." Further confirmation was provided by Morton and coworkers," who investigated the stereochemistry of the proton-induced nucleophilic substitution on (5)-(- -)- and (R)-(— )-2-butanol in the gas-phase at 10 torr in their 70-eV EBF radiolysis reactor. In the presence of a strong base, i.e., tri-n-propylamine... 

Electron transfer-induced nucleophilic addition to several otho cyclopropane compounds was also studied. The nucleophilic addition of methanol to quadricy-clane radical cation 8 produces the two methanol adducts 53 and 54. The stereochemistry of the methoxy groups in these structures identifies the preferred direction of nucleophilic attack upon the intermediate radical cations 8. Detailed NOE experiments delineate the structure of 53 and establish conclusively that the norbomene derivative 54 contains a 7-fl ri-methoxy group. The stereochemistry of both is compatible with stereospecific nucleophilic attack exclusively firom the exo-position. 7-Methylenequadricyclane also is attacked exclusively from the exo-face.These results can be explained via backside attack with inversion of configuration. 

Stereochemistry Inversion and racemization Inversion (backside attack)... 

Typically, Sn2 reaction requires a backside attack. The C—X bond weakens as nucleophile approaches. All these occur in one step. This is a concerted reaction, as it takes place in a single step with the new bond forming as the old bond is breaking. The Sn2 reaction is stereospecific, always proceeding with inversion of stereochemistry. The inversion of... 

Control of regio- and stereochemistry in the synthesis of substituted azepanes has been achieved via piperidine ring expansion methodology and aziridinium ion intermediates. Thus, reaction of 30 with azide ion afforded 32 exclusively with backside attack by the azide ion at the methine carbon in the intermediate 31 being preferred [02JCS(P1)2080],... 

Carbon-centered nucleophiles can also be used to advantage in the reaction with epoxides. For example, the lithium enolate of cyclohexanone 96 engages in nucleophilic attack of cyclohexene oxide 90 in the presence of boron trifluoride etherate to give the ketol 97 in 76% yield with predominant syn stereochemistry about the newly formed carbon-carbon bond <03JOC3049>. In addition, a novel trimethylaluminum / trialkylsilyl triflate system has been reported for the one-pot alkylation and silylation of epoxides, as exemplified by the conversion of alkenyl epoxide 98 to the homologous silyl ether 99. The methyl group is delivered via backside attack on the less substituted terminus of the epoxide <03OL3265>. 

Which product is formed in an Sn2 reaction When the stereochemistry of the product is determined, only B, the product of backside attack, is formed. 

HMPA at 65 C for 3 hours affords the corresponding trans and cis olefins, respectively. Backside attack of Mc3SiK on the cis (and trans) epoxides generates the threo- (and erythro-) jS-alkoxysilanes, respectively, followed by syn elimination (Peterson elimination) to give the olefin with inverted stereochemistry. 

A third mechanism for substitution at C(sp3)-X bonds under basic conditions, elimination-addition, is occasionally seen. The stereochemical outcome of the substitution reaction shown in the figure tells us that a direct Sn2 substitution is not occurring. Two sequential Sn2 reactions would explain the retention of stereochemistry, but the problem with this explanation is that backside attack of MeO- on the extremely hindered top face of the bromide is simply not reasonable. The SrnI mechanism can also be ruled out, as the first-row, localized nucleophile MeO- and the 2° alkyl halide are unlikely substrates for such a mechanism. 

Whenever you see retention of stereochemistry, you should think double inversion, and in fact double inversion occurs in this reaction. The Pd(0) complex acts as a nucleophile toward the allylic carbonate or acetate, displacing MeOCC>2 or AcO by backside attack and giving an allylpalladium(II) complex. The nucleophile then attacks the allylpalladium(II) complex, displacing Pd by backside attack to give the product and regenerate Pd(0). The regio-chemistry of attack (Sn2 or Sn2 ) is dependent on the structure of the substrate. 

A backside attack of C02> on the alkyl carbon, analogous to the SO2 insertion mechanism was ruled out by studies of the a-carbon stereochemistry upon insertion (25). The insertion of CO2 into the metal carbon bond of threo-cis-W(CO) (L)(CHD-CHD-Ph) (L = CO and PMc3) proceeds with retention of configuration at the a-carbon (Scheme 1) (26). This is in contrast to the inversion of configuration at the alpha carbon found in backside SO2 insertion reactions. 

In 2004, Knoll and Bennet41 reported a study of the aqueous methanolysis of the a-3,4-dihydro-2H-pyrano[3,2-c]pyridinium A-glycoside of NeuAc 3 (Scheme 16). This study was aimed at addressing the possibility that the NeuAc carboxylate group plays a nucleophilic role in the overall displacement process at the anomeric center. One would predict that overall retention stereochemistry would be observed in a two-step displacement process involving initial intramolecular attack by the carboxylate group, followed by backside attack from solvent (Scheme 17). Solvolysis of... 

Look at AlClj as a Lewis acid and benzene as a nucleophile. Recall (.Section 9-0) that acid-catalyzed ring openings of oxacyclopropanes give Sul regio-chemistry (most stable carbocation) but Sn2 stereochemistry (backside nucleophilic attack). So. 

The stereochemistry is also affected by the solvent polarity (Scheme 26). The reaction using (5)-l-phenyl-l-(trifluorosilyl)ethane of 38% ee at 60 °C resulted in retention (23% ee, S) in THF, but inversion (8% ee, R) in HMPA-THF (1 10). Higher temperature and polar solvents are considered to change the reaction mechanism of transmetallation from a four-centered transition state [Se2 (cyclic)] to a backside attack of the paUadium(II) complex [Se2 (open)] (Scheme 27). 

Addition via bridged intermediates is characterized by anti stereochemistry, since the nucleophile opens the ring by backside attack ... 

In some cases, reactions of electrophiles with metal-alkyl complexes possessing d-elec-trons appear to occur by mechanisms. - " In this process, the electrophile can attack the frontside or backside of the alkyl group. Although retention of stereochemistry at the metal-bound carbon from frontside attack at the metal-carbon bond is often observed, inversion of stereochemistry from backside attack at this carbon has also been observed. 

Cleavage of metal-alkyl bonds in d° metal complexes, therefore, occur by an 5 2 mechanism involving direct attack on the metal-alkyl bond. The product of this process is usually formed with retention of stereochemistry at carbon. This stereochemistry implies that the electrophile reacts by frontside attack at the M-C bond, rather than backside attack at the a carbon. Equation 12.21 shows an example of electrophilic attack on a (P metal complex that occurs with retention of configuration at the metal-carbon bond. The coordina-tive unsaturation of the 16-electron Zr(IV) complex may facilitate reaction with retention of configuration because it allows coordination of the incipient Br during the reaction, as depicted in Figure 12.1. 

The mechanism of the final step of C-0 bond formation by a formal reductive elimination was included as part of Chapter 11. In particular, two model systems have provided information on the mechanism of this reaction. First, the reaction orders, solvent effects, and electronic effects on the reductive elimination of methyl acetate and methyl aryl ethers from methylplatinum(lV) acetate and phenoxide complexes (Equation 18.16 and Scheme 18.4) indicated that these reductive eliminations occur by backside attack on a platinum methyl. Second, a study of the stereochemistry of the attack of water on a Pt(lV) alkyl showed that the formation of alcohol occurred with the inversion of configuration that reflects a backside attack. ... 

When substitution occurs by an Sn2 mechanism, the nucleophile directly attacks the substrate, with the angle of approach being 180" to the C-L bond. This is called "backside attack," and the reaction proceeds with inversion of stereochemistry, the so-called "Walden inversion." The C-L bond is being broken concurrently with the formation of the C-Nu bond, so both the substrate, R-L, and the nucleophile are involved in the transition state of the rate-determining step. Reactions in which two reactants are involved in the transition state of the rate-determining step are termed bimolecular, and the rate of such processes depends on the concentration of the substrate and the nucleophile, as shown in Equation 14.5, where k2 is the second-order rate constant. 

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