Anti Sn2 reaction

Figure 6.12 The anti-SN2 reaction of chloride with allyl chloride. While RHF theory does well with the reactant/product geometries, it significantly overestimates the C-Cl bond lengths in the C2 symmetric TS structure based on calculations at more reliable levels of theory...

Scheme 15 General Concept of 1,3-Chirality Transfer in an anti-SN2 Reaction 44-85-861...

The diastereoselective synthesis of a d ipeptide i sostere 221 was performed, through an organocopper mediated anti-SN2 reaction on substituted oxazolidinone 220 <020L1055>. 

We now know that the picture is not as simple as this, syn Sj[Pg.610]

There are also a few reactions showing more or less preference for an anti SN2 reaction, including a cyclopentane-forming reaction with an enolate nucleophile,589 and a sulfur nucleophile.590 In addition, the reactions of alkyl cuprates with allylic acetates are always stereospecifically anti 5.176 > 5.177, although the formation of racemic product shows that regiocontrol has been lost. 

With two more electrons, and rather more complicated structures, the Nazarov-like reactions of the carbamates 6.536 and 6.538 are conrotatory, with the torquoselectivity determined, as in the Favorskii reactions, by which side of the conjugated system the nucleofugal group departs from, clockwise as drawn for the carbamate 6.536 and anticlockwise for its diastereoisomer 6.538.964 The topological sense of the event in the left-hand ally lie system corresponds to an anti Sn2 reaction in both cases. 

Additions of oxygen and nitrogen nucleophiles to vinyloxiranes can be achieved with Pd(0) catalysis [103, 104]. Acetate, silanols, amines, sulfonamides, and azide have been used as nucleophiles, and the stereochemical outcome of these additions, where applicable, is normally the result of two consecutive SN2 reactions. This is demonstrated by the additions of NaNHTs to vinylepoxides 29 and 30, affording syn- and anti-amino alcohols 31 and 32, respectively, in good yields and with high diastereoselectivities (Scheme 9.22) [105]. 

A Lewis acid is involved in the reaction media when RCu BF3 or R3Al is used to cleave an acetal or ketal framework, and the resulting enol ether contains a E double bond. This is quite reasonable, since the overall reaction proceeds in an anti-SN2 manner. When a v>- -SN2 process is involved, the formation of products containing a Z double bond is observed60 (Table 2). The reaction of alkyllithium reagents with a./J-ethylcnic acetals and ketals proceeds in a. H7i-SN2 manner without assistance of Lewis acids, giving mainly the Z-products61-63. 

A similar salt effect is observed in the reaction of propargylic epoxides67. RMgBr in diethyl ether in the presence of 5% CuBr PBu, gave an anti-SN2 substitution product, whereas RMgCl in diethyl ether/pentane in the presence of 5% copper(I) bromide and chlorotrimethylsilane (1 equivalent) afforded a syn-SN2 substitution product (Table 3). 

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. 

Similar treatment explains the prevalence of the syw-mode 147>148) in a,y-interaction in Sn2 reactions (Fig. 7.37a). The a,5-interaction (e.g. Sn2 type reaction) is predicted to occur with syw-mode, and a,e-interac-tion with anti-mode (Fig. 7.37b and c). 

Fig. 39. Stabilizing orbital interactions involved in the syn and anti transition states of the Sn2 reaction...

Aminoallenes constitute an important class of functionalized allenes with interesting chemical properties. They are known as attractive substrates for constructing three- to six-membered azacycles [78]. In 1999, Ohno and co-workers reported the stereoselective synthesis of chiral a-aminoallenes 179 and 181 by RCu(CN)M-medi-ated anti-SN2 substitution of chiral 2-ethynylaziridines 178 and 180 (Scheme 4.47) [79]. The X-ray data and specific rotations of the allenes were consistent with a net anti-S- 2 substitution reaction. 

Trialkyl- or triarylallenyltin compounds can also be prepared by Sn2 displacement of propargylic mesylates with various stannylcopper reagents in THF (Eq. 9.82) [71]. This reaction is postulated to proceed by an anti Sn2 pathway based on the stereochemical relationship between the enantioenriched mesylate and the allenic product (Eq. 9.83). The allene obtained from the reaction of the mesylate of (R)-3-phenyl-l-propyn-3-ol with Ph3SnCu was assigned the (P) configuration from a consideration of the observed optical rotation and an application of Brewster s rules [71]. 

A diastereoselective synthesis of the racemic vinylallene 96 was described by Gordon and Tabacchi [96] in 1992 (Scheme 18.31). Here, the exocyclic allene was formed via anti-SN2 -substitution of the propargylic sulfmate 98 with lithium diisopropenyl-cyanocuprate, which, however, was also found to undergo side reactions such as reduction and direct attack of the nucleophile at the sulfmate. Deprotection of the substitution product 99 (which was obtained with only 35% yield) finally provided the desired target molecule 96. 

The idea that the stereochemical outcome of an intramolecular enolate alkylation is determined by chelation in the transition state was recently demonstrated by Denmark and Henke, who observed a marked preference for a "closed transition state (coordination of the cationic counterion to an enolate and the developing alcohol) resulting in a syn product. For example, the highest syn anti ratio (89 11) was obtained in toluene and the lowest syn.anti ratio (2 98) was obtained with a crown ether. These observations parallel the facial selectivities described herein and in ref 11 on the intramolecular SN2 reaction see (a) Denmark, S. A. Henke, B. R. J. Am. Chem. Soc. 1991, 113, 2177. (b) Denmark, S. A. Henke, B. R. J. Am. Chem. Soc. 1989, 111, 8022. 

Anti hydroxylation can be achieved by treatment with H202 and formic acid. In this case, epoxidation (5-36) occurs first, followed by an Sn2 reaction, which results in overall anti addition ... 

Alkenes may also react with certain oxidizing agents to result in anti hydroxyla-tion. Treatment with peroxycarboxylic acids435 leads initially to an epoxide. Ring scission of the latter via an SN2 reaction in an anti manner with the corresponding carboxylic acid or water gives the trans monoester or tram diol, respectively. Complete anti stereoselectivity and high yields in the oxidation of cycloalkenes are... 

For instance, the rate of SN2 reaction is greatly enhanced in a-haloethers 62 and in a-haloketones 63. This enhancement should however occur only when the oxygen atom in 62 has an electron pair anti peri planar to the C — Cl bond (cf 64+ 65). Similarly, in an o-haloketone the it system of the carbonyl group must be parallel to the C —Cl bond (cf, 66 67) (20). 

The term stereoselective is often confused with the term stereospecific, and the literature abounds with views as to the most satisfactory definition. To offer some clarification, it is perhaps timely to recall a frequently used term, introduced a decade or so ago, namely the stereoelectronic requirements of a reaction. All concerted reactions (i.e. those taking place in a synchronised process of bond breaking and bond forming) are considered to have precise spatial requirements with regard to the orientation of the reactant and reagent. Common examples are SN2 displacement reactions (e.g. Section 5.10.4, p. 659), E2 anti) elimination reactions of alkyl halides (e.g. Section 5.2.1, p.488), syn (pyrolytic) elimination reactions (Section 5.2.1, p.489), trans and cis additions to alkenes (e.g. Section 5.4.5, p. 547), and many rearrangement reactions. In the case of chiral or geometric reactants, the stereoisomeric nature of the product is entirely dependent on the unique stereoelectronic requirement of the reaction such reactions are stereospecific. 

---