Sn2 attack

Sn2 attack of the electron-rich platinum(O) on the alkyl halide to give the Ptn(R)X species directly, possibly via an ionic intermediate. 

The reaction does not feature a bimolecular step, such as direct Sn2 attack of the hydroxide nucleophile on the cobalt center. Rather, hydroxide ion participates in a prior-equilibrium reaction, and the actual rate-controlling reaction is believed to be the uni-molecular expulsion of the leaving group from a species that contains a coordinated... 

That is, the difference between the mechanisms of action of the two bases lies in the ability of EtsN to add to the Vilsmeier-Haack adduct to form a tetrahedral intermediate, susceptible to Sn2 attack by (at least partially de-protonated) cellulose. This leads to formation of the desired Cell - Tos. 

Substitution of the free epoxide, which generally occurs under basic or neutral conditions, usually involves an Sn2 mechanism. Since primary substrates undergo Sn2 attack more readily than secondary, unsymmetrical epoxides are attacked in neutral or basic solution at the less highly substituted carbon, and stereospecifically, with inversion at that carbon. Under acidic conditions, it is the protonated epoxide that undergoes the reaction. Under these conditions the mechanism can be either SnI or Sn2. In S l mechanisms, which favor tertiary carbons, we might expect that attack would be at the more highly substituted carbon, and this is indeed the case. However, even when protonated epoxides react by the 8 2 mechanism, attack is... 

Fluorination with retention of configuration (such as in 327) has often been attributed to steric crowding on the opposite side of the hydroxyl group, hindering the back side of the fluoride ion for Sn2 attack. However, a possible Sn/ mechanism by loss of an OSp2NEt2 fragment to give a car-bonium cation, followed by front-side attack of fluoride ion, should be... 

Under (i) the square and pyramidal complexes are often easier to substitute than the octahedral complexes for the obvious reason that they have open residual coordination sites, looking upon all the complexes as derived from an octahedron. The mechanism of substitution can then be the typical organic Sn2 attack. More usually the reactions of complex ions proceed by predissociation, SnI, so that the important consideration is that c and d should be at least relatively good leaving groups. 

In seeking an explanation for the implied changeover in mechanistic pathway we need to consider, in each case, the effect on the transition state of both electronic and steric factors. For SN2 attack, the enhanced inductive effect of an increasing number of methyl groups, as we go across the series, might be expected to make the carbon atom that... 

Sn2 attack on the CH2 in (10) is found to proceed at very much the same rate as on that in MeCH2Cl, suggesting that any adverse steric crowding in the T.S. by the bulky C6H5 group is compensated by a small electronic (inductive ) effect promoting reaction. 

All are tertiary halides so that attack by the S mode would not be expected to occur on (16) or (17) any more than it did on (8) (cf. p. 82). Sn2 attack from the back on the carbon atom carrying Br would in any case be prevented in (16) and (17) both sterically by their cagelike structure, and also by the impossibility of forcing their fairly rigid framework through transition states with the required planar distribution of bonds to the bridgehead carbon atom (cf. p. 84). Solvolysis via rate-limiting formation of the ion pair (SN1), as happens with (8) is... 

Initial attack by base on (34) yields the alkoxide anion (36), internal attack by this ROe then yields the epoxide (37) with inversion of configuration at C (these cyclic intermediates can actually be isolated in many cases) this carbon atomf, in turn, undergoes ordinary SN2 attack by eOH, with a second inversion of configuration at C. Finally, this second alkoxide anion (38) abstracts a proton from the solvent to yield the product 1,2-diol (35) with the same configuration as the starting material (34). This apparent retention of configuration has, however, been brought about by two successive inversions. 

By contrast, O in (43) is sufficiently electronegative not to donate an electron pair (unlike Oe in ROe and RCO20 above), and hydrolysis of EtOCH2CH2Cl thus proceeds via ordinary SN2 attack by an external nucleophile—which is likely to be very much slower than the internal nucleophilic attack in (42) — (44). That a cyclic sulphonium salt such as (44) is involved is demonstrated by the hydrolysis of the analogue (45), which yields two alcohols (the unexpected one in greater yield) indicating the participation of the unsymmetrical intermediate (46) ... 

The arguments presented herein lend the strongest support to SN2 attack by G-N7 at the amide nitrogen of /V-acyloxy-/V-alkoxyamides and for pathway (i) in Scheme 23 rather than pathway (iii) in which, once bound to DNA, the mutagens undergo SnI formation of reactive nitrenium ion. 

The carbonyl O of esters, amides, and the like is always more nucleophilic than any other heteroatom attached to the carbonyl C. The first protonation occurs at the carbonyl O. An SN2 attack of I- on CH3 then gives the free carboxylic acid. 

The reaction of CIO- with methyl chloride can only proceed via the Sn2 process. An inverse KIE of 0.85 is measured (Table 10.3). The reaction with /-butyl chloride presumably proceeds via an E2 mechanism (since Sn2 attack on the Cl substituted carbon is blocked) and the observed KIE of 2.31 (Table 10.3) is consistent with that conclusion. The isotope effects for both species are nearly the same as the effects measured in the condensed phase (compare Tables 10.3 and 10.4) and measure the relative contributions of the two paths. The results indicate that the E2 pathway becomes the dominant channel as the substrate becomes more sterically hindered. 

With the reagent PhCu in the presence of the additives BF3 and PBU3, ees of up to 95% were obtained, while values of up to 85% were achievable with a vinyl copper reagent. Chiral dienic acetals have also been studied three regioisomeric products could be obtained in this case as the result of Sn2, Sn2, or Sn2" attack of the organocopper reagent [25]. Mixtures were indeed obtained with alkyl copper reagents, but PhCu BFs resulted in formation of only the Sn2 and Sn2" products, with selectivity for the latter (Scheme 8.12). 

Ethers containing substituted all rl groups (secondary or tertiary) may also be prepared by this method. The reaction involves Sn2 attack of an alkoxide ion on primary alkyl halide. 

Attempts to establish the structure of the initial adduct by NMR-spectroscopy failed because of the low solubility of 27. This makes it impossible to draw a clear conclusion as to whether the ammonia adds to C-6 (as occurs in the case of the A-methylpyrimidinium salts) or at C-2. Since NMR spectroscopy of a solution of 4,6-diphenylpyrimidine in potassium amide/liquid ammonia strongly supports the formation of an anionic C-2 adduct (75UP1], it is justified to assume that also in the deamination of 27 by liquid ammonia, a C-2 adduct 28 is involved (Scheme III. 16). It is evident that the major part of the deamination (73%) does not involve a ringopening reaction the main deamination reaction occurs by an Sn2 attack of ammonia on the A-amino group in 27. A similar mechanism has also been postulated in the deoxygenation of pyrimidine A-oxides, when they are heated with liquid ammonia (Scheme III.16) [77UP2]. 

In the initial step of the polymerization, a cyclic oxonium ion is formed by transfer of an alkyl group from the initiator to the cyclic ether. Propagation occurs by SN2 attack of a monomer molecule at a ring a-methylene position of the cyclic tertiary oxonium ion, followed by opening of the oxonium ring and formation of a new cyclic oxonium ion. 

The possible pathways for the transformations 323 -> 324 and 323 - 325 are outlined in Scheme 84. The first step that is common to these reactions involves the electrophilic attack of the I(III) species on the enol form of 323 at the face of the molecule anti to the C(2)-aryl ring to provide intermediate 328. Routes (a) and (a ) involving a 1,2-aryl shift lead to isoflavones 324. Route (b), involving Sn2 attack of X /XH at the C(3)-position of intermediate 328, leads to 325 via 329. The nucleophilicity of X XH plays a deciding role in affecting the course of the reaction. 

The use of TMOF as a solvent provides strong acetalizing conditions (323 330). This allows the generation of enol ether 331, which on electrophilic attack of hypervalent iodine species [PhI(OMe)2] (83IC1563) gives intermediate 332. Nucleophilic attack of the solvent at the C(4)-position of 332, followed by migration of ring A, results in the formation of 326. The minor product 327 is resulted by a Sn2 attack of methanol at the C(3)-position of 333 (Scheme 85). 

Since chloroalkanes are not reduced at the cathode potential used, it is concluded that these reactions involve generation of a carbaiiion by dissociative electron transfer to the most easily reduced carbon-halogen bond followed by Sn2 attack of this carbanion on the second carbon-halogen bond [91]. 

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