SN2-type displacement reactions

The propensity of the cesium salts of week acids to accelerate SN2 type displacement reactions was exploited for the stereodirected conversion of glycosyl nitrates into anomeric phosphotriesters by exposure of phosphoric acid diesters to cesium salts (Scheme 9).16 Thus, glycosyl nitrate 50, obtained by azidonitration of 3,4-di-O-acetyl-L-fucal, was treated with... 

Lewis acid-mediated SN2-type displacement reactions of RMgX have been used for asymmetric synthesis of 2-substituted piperidines,111 and BeCl2 has been found to promote addition of RLi and RMgX to cyclohex-2-enone.112... 

If controlled conditions and an aptotic polar solvent are used, a SN2-type displacement reaction can be performed to give the inverted anomeric configuration in the product, e.g. a-glycosides from P-glycosyl halide precursors, in spite of the presence of participating 2-0-protecting groups (Scheme 3) [26, 27). 

The use of tetra-n-butylammonium fluoride (54) in an aprotic solvent such as acetonitrile may be more advantageous. Foster and colleagues (19, 37) have effected an SN2 type of reaction using this reagent in the conversion of l,2 5,6-di-0-isopropylidene-3-0-p-tolylsulfonyl-D-allofura-nose into the C-3 epimeric fluorodeoxy derivative. Note that whereas potassium fluoride is ineffective in displacing secondary sulfonate esters in sugars, tetra-n-butylammonium fluoride is capable of effecting a displacement with Walden inversion even in a furanose drivative. 

On the other hand, in the case of a-halogenoethyl sulphoxides 503 an SN2-type displacement occurs with mercaptide anions and leads to a-alkylthioethyl sulphoxides 504, while the elimination-addition mechanism is operative with alkoxide anions, affording jS-alkoxyethyl sulphoxides577,596 505 (equation 306). Finally, the reaction of 1-halogeno-l-methylethyl derivatives with both nucleophiles mentioned above occurs via the elimination-addition mechanism596 (equation 307). The substitution reaction can also take place intramolecularly (equation 308) and it proceeds very easily (cf. Section IV.A.2.C)484,600. 

The most common leaving groups are sulfonate esters and halides. For the sake of convenience, the discussion of certain dehalogenation reactions is also included in this section even though they may not involve SN2 type displacement. Benzylic alcohols are also known to be displaced by hydrides or deuterides, but there is no evidence for the application of these reactions to the steroid field. 

The displacement of homoallylic tosylates follows an entirely different course with a strong tendency for the formation of cyclo steroids. Thus, when the 3/ -tosylate of a A5-steroid (187) is treated with lithium aluminum deuteride, the product consists mainly of a 3j5-drA5-steroid (188) and a 6 -d1-3,5a-cyclo steroid (189).15,51 The incorporation of deuterium at the 3/ position in (188) indicates that this reaction proceeds via a 3,5-cyclo cholesteryl cation instead of the usual SN2 type displacement sequence. This is further substantiated by the formation of the cyclo steroid (189) in which the deuterium at C-6 is probably in the / configuration.51... 

The formation and the hydrolysis of acyclic and cyclic acetals have been studied in rather great detail [91]. Several reviews on this topic are available [92] and some comments have been made [13] concerning the carbohydrate series. We have shown in Schemes 1,2, and 3 that a common feature of this reaction seems to be the intermediacy of an oxocarbenium ion. However, the cyclization of such an intermediate has been questioned more recently [93] in the light of the Baldwin s rules for ring closure [94]. At least for the five-membered ring, an SN2-type displacement mechanism far the protonated form (B) of die hemiacetal (A) (favorable 5-exo-tet cyclization) has been proposed rather than the unfavorable 5-endo-trig cyclization of the oxocarbenium ion (C) (Scheme 5). Except when the formation of the enol ether (D) is structurally impossible, the intermediacy of such a compound remains feasible. 

The formation of a prepolymer involves two different kinds of reactions. One is an SN2-type displacement, and the other is oxide-ring opening of the product by attack of more bisphenol A. Usually, for practical purposes the degree of polymerization n of the prepolymer is small (5 to 12 units). 

Limited to three- and four-membered rings. Reaction is an SN2-type displacement (Section 14-12A). Oxa-cyclopropanes often are used as a means of increasing chain length by two carbons in one step. A major side product is a haloalcohol,... 

In these rearrangements, there are two consecutive internal SN2 type displacement processes a) an electron pair of the oxygen atom displaces the electron pair of a C —C bond and b) the electron pair of a C—C bond displaces the leaving group. It is therefore pertinent to find out if these processes follow the stereoelectronic principle of the SNj reaction. 

In Chapter 4 we pointed out that Sn2 type displacements are characteristic of reagents which contain an atom with an unshared pair of electrons. Thus hydroxide ion, alkoxides, amines, halide ions, and car-boxylate ions commonly effect displacements at a saturated carbon atom. Carbanions also bring about the same reaction ... 

The most logical interpretation of such results is to consider that the reaction proceeds by the simultaneous operation of two processes.3 One is a normal Sn2 type displacement which gives only primary products from primary starting materials and secondary products from secondary starting materials. The other is an Sn 1-like process in which reaction of the intermediate carbonium ion can occur through the resonance structures VI or VII to give crotyl or methylvinylcarbinyl products ... 

In the following years, studies conducted by Sharpless,6 7 Bach,8,9 Curci,10 and others11 relied on reaction kinetics to formulate support of a SN2-type displacement by the nucleophilic substrate on the electrophilic oxygen atom of the three-membered ring. Similarly, the deoxygenation of oxaziridines, such as 1, is kinetically consistent with the aforementioned Sn2 mechanism. 

The Pd(0)-catalyzed reactions of propargylic compounds can be understood by the following mechanistic consideration.t" Complex formation by a stoichiometric reaction of propargylic chlorides with Pd(Ph3P)4 has been studied, and cr-allenylpalladium and propargylpalladium (or o--prop-2-ynylpalladium) were isolated as yellow powder (Scheme 7r-Allenylpalladium chloride is formed by Sn2 type displacement of the... 

The carbonyl carbon is trigonal and sp hybridized. As we have seen in the reactions of alkenes and benzenes (Chapters 12 and 15), the substitution mechanisms associated with saturated, tetrahedral, ip -hybridized carbon atoms do not typically occur in unsaturated, trigonal planar systems. Their planarity renders backside, SN2-type displacement geometrically difficult, and sp -hybridized carbon atoms form poor carbocations, disfavoring SnI. 

The unique chemical behavior of KO2 is a result of its dual character as a radical anion and a strong oxidizing agent (68). The reactivity and solubiHty of KO2 is gready enhanced by a crown ether (69). Its usefiilness in furnishing oxygen anions is demonstrated by its appHcations in SN2-type reactions to displace methanesulfonate and bromine groups (70,71), the oxidation of benzyHc methylene compounds to ketones (72), and the syntheses of a-hydroxyketones from ketones (73). 

We consider first the Sn2 type of process. (In some important Sn2 reactions the solvent may function as the nucleophile. We will treat solvent nucleophilicity as a separate topic in Chapter 8.) Basicity toward the proton, that is, the pKa of the conjugate acid of the nucleophile, has been found to be less successful as a model property for reactions at saturated carbon than for nucleophilic acyl transfers, although basicity must have some relationship to nucleophilicity. Bordwell et al. have demonstrated very satisfactory Brjinsted-type plots for nucleophilic displacements at saturated carbon when the basicities and reactivities are measured in polar aprotic solvents like dimethylsulfoxide. The problem of establishing such simple correlations in hydroxylic solvents lies in the varying solvation stabilization within a reaction series in H-bond donor solvents. 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

However, if we consider the alternative nucleophilic displacement, it is known that nucleophilic processes are accelerated by ionic liquids, but more pertinent is the fact that the Sn2 displacement of iodide from alkyl iodide (Mel) by Rh(CO)2l2 is slightly accelerated by ionic liquids (7). Unfortunately, ionic liquids would also be expected to accelerate the nucleophilic displacement of iodide from ethyl iodide by propionic acid to form ethyl propionate (Reaction 8). In fact, as an Sn2 Type II displacement (the interaction of two neutral species), the ester formation from propionic acid and ethyl iodide would be expected to be significantly increased compared to the reaction of Rh(CO)2l2 with EtI. Therefore, by operating in iodide containing ionic liquids, we had set up a situation in which we suppressed the normally predominant hydride mechanism, slightly accelerated the alternative nucleophilic mechanism, but dramatically increased the ethyl propionate by-product forming pathway. 

Thus solvolysis of (+)C6HsCHMeCl, which can form a stabilised benzyl type carbocation (cf. p. 84), leads to 98% racemisation while (+)C6H13CHMeCl, where no comparable stabilisation can occur, leads to only 34% racemisation. Solvolysis of ( + )C6H5CHMeCl in 80 % acetone/20 % water leads to 98 % racemisation (above), but in the more nucleophilic water alone to only 80% racemisation. The same general considerations apply to nucleophilic displacement reactions by Nu as to solvolysis, except that R may persist a little further along the sequence because part at least of the solvent envelope has to be stripped away before Nu can get at R . It is important to notice that racemisation is clearly very much less of a stereochemical requirement for S l reactions than inversion was for SN2. 

It is interesting that when EtOe, in fairly high concentration, is used as the nucleophile in preference to EtOH, the reaction of (19) becomes SN2 in type and yields only the one ether (21). Allylic rearrangements have been observed, however, in the course of displacement reactions that are proceeding by a bimolecular process. Such reactions are referred to as SN2 and are believed to proceed ... 

---