Sn2 stereochemistry

For 8-NH-Boc-Y-mesyloxy-a, 3-enoates, only anti-SN2 substitution has been observed. However, when the NH is absent, such as in Pro-derived enoates, or Ser and Thr acetonide-derived enoates 88 or 89 (Scheme 17), the syn-SN2 stereochemistry has also been observed. 93 ... 

Higher reactivity of 1,3,2-dioxathiolane j/A-dioxides (cyclic sulfates) toward nucleophiles, and practically guaranteed Sn2 stereochemistry of G-O bond cleavage, make them extremely useful synthetic intermediates <1996CHEC-II(4)545, 1997AHC89, 2000T7051>. The starting cyclic sulfates and the products of their reactions with O-nucleophiles are summarized in Table E... 

SN1 stereochemistry Mixture of retention and inversion racemization. Sn2 stereochemistry Complete inversion. 

Sn1 and Sn2 Stereochemistry Sections 8.4D.1 and E.1 Sn2 reactions proceed with inversion of configuration. Since both starting materials were optically active, the products are also optically active. 

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. 

Mechanism of Enolate Alkylation SN2 reaction, inversion of electrophile stereochemistry... 

The cleavage reaction occurs in three steps O protonation of the epoxide, Sn2 nucleophilic attack on the protonated epoxide, and deprotonation of the ring-opened product. Draw the complete mechanism. How many intermediates are there Which step determines diol stereochemistry ... 

Thomson I. Click Organic Process to view an animation showing the stereochemistry of the Sn2 reaction. 

Problem 11.2 What product would you expect to obtain from SN2 reaction of OH- with (k)-2-bromo-butane Show the stereochemistry of both reactant and product. 

From what alkyl bromide was the following alkyl acetate made by SN2 reac tion Write the reaction, showing all stereochemistry. 

One of the most important reasons for using tosylates in S j2 reactions is stereochemical. The S]s]2 reaction of an alcohol via an alkyl halide proceeds with hvo inversions of configuration—one to make the halide from the alcohol and one to substitute the halide—and yields a product with the same stereochemistry as the starting alcohol. The SN2 reaction of an alcohol via a tosylate, however, proceeds with only one inversion and yields a product of opposite stereochemistry to the starting alcohol. Figure 17.5 shows a series of reactions on the R enantiomer of 2-octanol that illustrates these stereochemical relationships. 

Iodine azide, generated in situ from an excess of sodium azide and iodine monochloride in acetonitrile, adds to ethyl l//-azepine-l-carboxylate at the C4 — C5 and C2 —C3 positions to yield a 10 1 mixture of the rw-diazidodihydro-l//-azepines 1 and 2, respectively.278 The as stereochemistry of the products is thought to be the result of initial trans addition of the iodine azide followed by an SN2 azido-deiodination. The diazides were isolated and their stereochemistry determined by conversion to their bis-l,3-dipolar cycloadducts with dimethyl acetylene-dicarboxylate. 

Treatment of cyclic vinylaziridine 105 with organocuprates of the R2CuLi type proceeds in a highly syn-selective manner (Scheme 2.29) [46], The syn stereochemistry of the reaction reflects the effect of the acetonide group, which directs the nucleophilic attack to the less hindered a-face. The formation of SN2 products 109 from the cyclic (chlorovinyl)aziridine 107 can be explained by assuming a syn-SN2 ... 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

A similar reaction the with rran.v-isomer 3b gave c -3,5-dimethylcyclohexene (4) with very high diastereoselectivity. Accordingly, the stereochemistry of this substitution is anti. Deuterium labeling experiments using the 1-deuterio or 3-deuterio derivative of 3 a showed that the ratio of SN2 /SN2 with lithium dimethylcuprate was about 50 50, while the ratio with lithium cyano(methyl)cupratc was >96 4. 

In this scheme, RS and SR represent enantiomers, and so on, and 5 represents some fraction. The following are the possibilities (1) Direct attack by SH on RX gives SR (complete inversion) in a straight Sn2 process. (2) If the intimate ion pair R X is formed, the solvent can attack at this stage. This can lead to total inversion if Reaction A does not take place or to a combination of inversion and racemization if there is competition between A and B. (3) If the solvent-separated ion pair is formed, SH can attack here. The stereochemistry is not maintained as tightly and more racemization (perhaps total) is expected. (4) Finally, if free R" " is formed, it is planar, and attack by SH gives complete racemization. 

The stereochemistry of Sn2 reactions has been investigated. It has been found that both syn " (the nucleophile enters on the side from which the leaving group departs) and anti ° reactions can take place, depending on the nature of X and though the syn pathway predominates in most cases. 

No matter how produced, RN2 are usually too unstable to be isolable, reacting presumably by the SnI or Sn2 mechanism. Actually, the exact mechanisms are in doubt because the rate laws, stereochemistry, and products have proved difficult to interpret. If there are free carbocations, they should give the same ratio of substitution to elimination to rearrangements, and so on, as carbocations generated in other SnI reactions, but they often do not. Hot carbocations (unsolvated and/or chemically activated) that can hold their configuration have been postulated, as have ion pairs, in which OH (or OAc , etc., depending on how the diazonium ion is generated) is the coun-... 

The stereochemistry at the migration origin A is less often involved, since in most cases it does not end up as a tetrahedral atom but when there is inversion here, there is an Sn2 type process at the beginning of the migration. This may or may not be accompanied by an Sn2 process at the migration terminus B ... 

For example, let s look at the stereochemistry of SnI reactions. We already saw that Sn2 reactions proceed via inversion of configuration. But SnI reactions are very different. Recall that a carbocation is sp hybridized, so its geometry is trigonal planar. When the nucleophile attacks, there is no preference as to which side it can attack, and we get both possible configurations in equal amounts. Half of the molecules would have one configuration and the other half would have the other configuration. We learned before that this is called a racemic mixture. Notice that we can explain the stereochemical outcome of this reaction by understanding the nature of the carbocation intermediate that is formed. 

The mechanisms of SnI and Sn2 reactions helped us understand the stereochemistry of each reaction, and we were also able to see why we call them SnI and Sn2 reactions (based on reaction rates that are justified by the mechanisms). So, the mechanisms really do explain a lot. This should make sense, because a proposed... 

Secondary bromides and tosylates react with inversion of stereochemistry, as in the classical SN2 substitution reaction.24 Alkyl iodides, however, lead to racemized product. Aryl and alkenyl halides are reactive, even though the direct displacement mechanism is not feasible. For these halides, the overall mechanism probably consists of two steps an oxidative addition to the metal, after which the oxidation state of the copper is +3, followed by combination of two of the groups from the copper. This process, which is very common for transition metal intermediates, is called reductive elimination. The [R 2Cu] species is linear and the oxidative addition takes place perpendicular to this moiety, generating a T-shaped structure. The reductive elimination occurs between adjacent R and R groups, accounting for the absence of R — R coupling product. 

The stereoselective total synthesis of (+)-epiquinamide 301 has been achieved starting from the amino acid L-allysine ethylene acetal, which was converted into piperidine 298 by standard protocols. Allylation of 297 via an. V-acyliminium ion gave 298, which underwent RCM to provide 299 and the quinolizidine 300, with the wrong stereochemistry at the C-l stereocenter. This was corrected by mesylation of the alcohol, followed by Sn2 reaction with sodium azide to give 301, which, upon saponification of the methyl ester and decarboxylation through the Barton procedure followed by reduction and N-acylation, gave the desired natural product (Scheme 66) <20050L4005>. 

Inversion of configuration can be also observed when the Sn2 reaction takes place at a stereocenter (with complete inversion of stereochemistry at the chiral carbon center) ... 

---