Backside displacement

Backside displacement is sterically blocked therefore, no SN2 reaction. 

The mechanisms of these acid-catalyzed epoxide openings are more complex than they at first appear. They seem to be neither purely SN1 nor SN2 but instead to be midway between the two extremes and to have characteristics of both. Take the reaction of 1,2-epoxy-l-methylcyclohexane with HBr shown in Figure 18.2, for instance. The reaction yields only a single stereoisomer of 2-bromo-2-methyl-cyclohexanol in which the —Br and —OH groups are trans, an S 2-li.ke result caused by backside displacement of the epoxide oxygen. But the fact that Br attacks the more hindered tertiary side of the epoxide rather than the less hindered secondary side is an SN1 -like result in which the more stable, tertiary carbocation is involved. 

The net effect of the addition/elimination sequence is a substitution of the nucleophile for the -Y group originally bonded to the acyl carbon. Thus, the overall reaction is superficially similar to the kind of nucleophilic substitution that occurs during an Sn2 reaction (Section 11.3), but the mechanisms of the two reactions are completely different. An SN2 reaction occurs in a single step by backside displacement of the Leaving group a nucleophilic acyl substitution takes place in two steps and involves a tetrahedral intermediate. 

Backbone (protein), 1028 Backside displacement. reaction and.363-364 von Baeyer, Adolf, 113 Baeyer strain theory, 113-114 Bakelile, structure of, 1218 Banana, esters in, 808 Barton, Derek, H. R., 389 Basal metabolic rate, 1169 Basal metabolism. 1169-1170 Base, Bronsted-Lowry, 49 Lewis, 57, 59-60 organic, 56-57 strengths of, 50-52 Base pair (DNA), 1103-1105 electrostatic potential maps of. 

The transformation proceeds with excellent stereoselectivity by kinetic formation of the 2,5-trans-disubstituted pyrrolidine 2-328 [182]. The tertiary amine can now initiate a nucleophilic backside displacement of the vicinal iodide in 2-328, leading to an aziridinium salt 2-329 [183]. This event ensures a net retention of the stereochemistry at C-13 in the following attack of the ester carbonyl in the butyrolactone ring closure to give 2-330. 

PA = 226 kcal moP ), the predominant formation (6.4 to 1) of the (7 ,5 )-di-2-butyl ether over the (R,R) and (5, 5 )-forms is attributed to a simple backside displacement in the proton-bound adduct of the starting 2-butanol enantiomer with inversion of configuration of the reaction site and loss of a molecule of water. When tri-n-propylamine is replaced by the less basic NH3 (PA = 196 kcal moF ), fast neutralization of the proton-bound dimers of the starting 2-butanol is prevented and, therefore, they can grow, producing aggregates that resemble solution microenvironments in which SnI pathways may be accessible as well. In them or in their primary substituted derivatives, consecutive nucleophilic displacements may take place. As a consequence, the stereospecificity of the process is lost and the [(R,S)-di-2-butyl ether]/[(7 ,7 )- and (5, 5 )-di-2-butyl ethers] ratio falls down to 1.2. In this case. 

The stereochemical consequences of front- and back-side displacements are different. With cyclic compounds, the two types of displacement lead to different products. For example, an SN2 reaction between cis-3-methylcyclopentyl chloride and hydroxide ion would give the cis alcohol by front-side approach but the trans alcohol by back-side approach. The actual product is the trans alcohol, from which we know that reaction occurs by backside displacement ... 

Nucleophilic aromatic substitution is much more restrictive in its applications than electrophilic aromatic substitution. In nucleophilic aromatic substitution, a strong nucleophile replaces a leaving group such as a halide. The mechanism cannot be the Sn2 mechanism because aryl halides cannot achieve the correct geometry for backside displacement. The aromatic ring blocks approach of the nucleophile to the back of the carbon bearing the halogen. 

Fig. 4. The reaction steps during nucleophilic substitution in the dilute gas phase. The upper route corresponds to backside displacement (the traditional SN2 mechanism) and the lower route is the frontside displacement mechanism. The latter is possible in weakly bonded RX+...

The stereochemistry of pyrazoline deazetizations is startling and, even now, difficult to understand. A case in point is the formation of bicyclo[2.1.0]pentane from 2,3-diazabicyclo[2.2.1]heptene. When the stereochemistry of the reaction is tested by introduction of labels at C(5) and C(6), it is found that product formation occurs with preferential inversion of configuration (Figure 49). Roth and Martin explained this in terms of backside displacement from a diazenyl biradicaP, but, as described above, the... 

Pmfs for the 8, 2 reaction of Cl -I- CH3CI were determined in water and DMF solution. The gas-phase MERP was obtained from ab initio calculations with the 6-31G(d) basis set the typical double-well form was found as illustrated in Fig. 1. The reaction coordinate has been defined as the difference in the two C-Cl distances since this provides symmetry about the transition state. The only energy minima for the linear backside displacement are the ion-dipole complexes 1, which flank the transition state 2,... 

The stereochemical outcome is known for many epoxide-opening reactions. Examination of the effects of substituents and conditions on stereochemistry can provide insight into the mechanisms of the rearrangements which are the focus of this section. The words syn and anti are used here to describe mechanistic features, with the terms cis and trans retained as structural descriptors. The vast majority of epoxide-opening reactions occur with anti stereospecificity, i.e. backside displacement of the cleaved C—O bond. Anti preference dominates sufficiently to warrant calling this the normal stereochemical outcome. 

The reaction of cyclohexene oxide with MeMgX was reexamined in 1969, in work which clearly established the importance of the halide. Standard conditions (1 h at 80 C) were employed with 1.4 equiv. of the organometallic, to give the yields listed under equation (83). Only minor amounts of the normal displacement product (200) are formed from the chloride and bromide, and none from the iodide. The iodide and bromide give extensive rearrangement, with the bromide being more selective in the sense that product (198) is expected on the basis of stereoelectronic considerations (backside displacement of halide) from the rra/is-halohydrin. The unusual product from this perspective is (199). It must arise either from the c/s-halohydrin or a process which is not subject to the same stereoelectronic controls, e.g. via a carbenium ion. 

The stereochemistry of the product obtained when 3-2,3-epoxycholestane is treated with MeMgl is in keeping with a mechanism involving initial diaxial opening to form an iodohydrin salt (equation 100), followed by rearrangement with backside displacement of the iodide via a twist boat conformer. Addition of MeMgl to the A-norsteroid aldehyde formed in this manner would then result in the two alcohols (epimeric at the carbinol center), which were isolated. 

With each isomer the course of reaction followed is the one which will permit a backside displacement of the chloride ion... 

The mechanism of the Ramberg-Backlund reaction is rather straightforward. When a-halosulfone 1 is treated with a strong base, deprotonation rapidly takes place to give a-anion 3, which undergoes a backside displacement (intramolecular nucleophilic substitution, SNi) to provide thiirane dioxide 4 (also known as episulfone) as the key intermediate.10 The Swi reaction with loss of halide is the rate-limiting step. Finally, the unstable 4 releases sulfur dioxide and the ring strain to deliver alkene 2. 

Another way of looking at this, which explains why anti-elimination is preferred from the antiperiplanar conformation, is that the electron pair from the breaking C—H bond displaces the bromide anion by backside attack. This keeps the incoming electrons and the outgoing electrons as far apart as possible. Just as backside attack by a nucleophile is favoured in the Sn2 mechanism, so backside displacement of the leaving group is favoured in the E2 elimination... 

The diastereoselectivity that arises from the intermediacy of a halonium ion has been exploited in a new type of reaction that produces lactone products. When 322 was treated with iodine and sodium bicarbonate, the initially formed iodonium ion (322) was opened by the carboxylate anion, generated by the reaction of bicarbonate with the acid moiety.Backside displacement of the iodonium ion led to the trans-relationship between the lactone ring and the iodide moiety in iodolactone 324. This reaction is commonly referred to as iodolactonization.251 This reaction can be extended to include bromolactonization and chlorolactonization. 

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