Oxygen nucleophiles stereochemistry

The regioselective ring-opening of vinyloxiranes by nitrogen nucleophiles offers an attractive route to vie-amino alcohols, compounds of much recent interest. As with oxygen nucleophiles, the stereochemistry of the reaction can be controlled by choice of reaction conditions aminolysis of 25, for example, affords anti-amino alcohol 26 in excellent yield and diastereoselectivity (Scheme 9.21) [48, 96, 97], and... 

Whereas oxygen nucleophiles gave poor yields of alkenylated products with alkenyl iodonium salts, the reactions with sulphur nucleophiles proceeded more efficiently, leading to unsaturated sulphides and sulphones. Thus, 4-t-butylcyclohexenyl phenyliodonium salts afforded with sodium thiophenoxide 4-t-butylcyclohexenyl phenyl sulphide (81%) [3] and with sodium phenylsulphinate the corresponding sulphone (29%) in the presence of 18-crown-6, the yield of the latter rose to 80% [45]. jS-Phenylsulphonylalkenyl iodonium salts with sodium phenylsulphinate at 0°C, without any catalyst, afforded Z-l,2-bis(phenylsulphonyl)alkenes, in high yield with retention of the stereochemistry [45] ... 

Intramolecular reactions of allylic acetates with conjugated dienes catalyzed by Pd(0) lead to a 1,4-addition of a carbon and an oxygen nucleophile to the diene. The reaction, which is formally an isomerization, involves tw different yr-allyl complexes (Scheme 8-4) [44]. Reaction of 22 in the presence of the Pd(0) catalyst Pd2(dba)3-CHCl3 (dba = dibenzyl-ideneacetone) and LiOAc/HOAc in acetonitrile at reflux produces the cyclized isomer 25 in 62% yield. The double bond was exclusively of E stereochemistry, while the ring stereochemistry was a mixture of cis and tram isomers. Oxidative addition of the Pd(0) to the allylic acetate gives the intermediate jr-allyl complex 23. Subsequent insertion of a diene double bond into the allyl-palladium bond produces another jr-allyl intermediate (24), which is subsequendy attacked by acetate to give the product 25. 

Inversion of the hydroxyl center with oxygen nucleophiles allows one to gain access to R) lactic acid derivatives. This strategy has been used to establish the correct stereochemistry in the alkylidene side chain of pumiliotoxin B (108) [37], a cardiac agent isolated from the Panamanian poison frog (Scheme 16). In the key reaction, conversion of 2 to R)-p-nitrobenzoyl ester 104 proceeds in high yield and with essentially complete inversion of configuration. 

Catalytic and stoichiometric additions of oxygen nucleophiles to coordinated dienes are summarized in Equations 11.33 and 11.34. Early studies involved 1,4-additions of two acetoxy or alkoxy groups across a diene. More recently, intermolecular additions of two different nucleophiles have been developed. The stereochemistry for additions across cyclic dienes makes this procedure particularly valuable. Conditions for either cis or trans additions have been developed. Cis addition is typically observed in the presence of added chloride, and trans addition occurs in the absence of chloride. Both intermolecular and intramolecular " 1,4 additions to dienes have been developed, and reactions of nitrogen and carbon nucleophiles have also been reported. More details on these processes are reported in Chapter 16. 

A stereochemical study reported by Henry illustrated that the formation of aldehyde and formation of chlorohydrin occur with different stereochemistry, and this result implies that one process occurs by syn addition and one by anti addition of water and palladium across the olefin. This study is summarized in Scheme 16.24. Oxidation of the non-race-mic, chiral allyl alcohol in the absence of added chloride forms the (R)-(E)-alcohol, whereas reaction of the allyl alcohol in the presence of added chloride forms the product with stereochemistry resulting from the opposite mode of attack. Because it is known that the allylic alcohol binds to palladium with hydrogen bonding between the hydroxyl group and the bound chloride, Henry concluded that the reaction conducted in the presence of high concentrations of added diloride occurs by external attack of the oxygen nucleophile, while the reaction with low concentrations of added chloride occurs by insertion of the olefin into a Pd-0 bond. ... 

An advantage that sulfonate esters have over alkyl halides is that their prepara tion from alcohols does not involve any of the bonds to carbon The alcohol oxygen becomes the oxygen that connects the alkyl group to the sulfonyl group Thus the configuration of a sulfonate ester is exactly the same as that of the alcohol from which It was prepared If we wish to study the stereochemistry of nucleophilic substitution m an optically active substrate for example we know that a tosylate ester will have the same configuration and the same optical purity as the alcohol from which it was prepared... 

Part B of Scheme 4.5 gives some examples of cyclizations induced by selenium electrophiles. Entries 9 to 13 are various selenyletherifications. All exhibit anti stereochemistry. Entries 14 and 15 are selenyllactonizations. Entries 17 and 18 involve amido groups as the internal nucleophile. Entry 17 is an 5-exo cyclization in which the amido oxygen is the more reactive nucleophilic site, leading to an iminolactone. Geometric factors favor N-cyclization in the latter case. 

The ammonium catalyst can also influence the reaction path and higher yields of the desired product may result, as the side reactions are eliminated. In some cases, the structure of the quaternary ammonium cation may control the product ratio with potentially tautomeric systems as, for example, with the alkylation of 2-naph-thol under basic conditions. The use of tetramethylammonium bromide leads to predominant C-alkylation at the 1-position, as a result of the strong ion-pair binding of the hard quaternary ammonium cation with the hard oxy anion, whereas with the more bulky tetra-n-butylammonium bromide O-alkylation occurs, as the binding between the cation and the oxygen centre is weaker [11], Similar effects have been observed in the alkylation of methylene ketones [e.g. 12, 13]. The stereochemistry of the Darzen s reaction and of the base-initiated formation of cyclopropanes under two-phase conditions is influenced by the presence or absence of quaternary ammonium salts [e.g. 14], whereas chiral quaternary ammonium salts are capable of influencing the enantioselectivity of several nucleophilic reactions (Chapter 12). 

The nucleophilic attack of the water or hydroxide species takes place in an anti fashion i.e. the oxygen attacks from outside the palladium complex and the reaction is not an insertion of ethene into the palladium oxygen bond. This has been demonstrated in a model reaction by Backvall [4], The reaction studied was the Wacker reaction of dideuterio-ethene (cis and trans) in the presence of excess of LiCl, which is needed to form 2-chloroethanol as the product instead of ethanal. The latter product would not reveal the stereochemistry of the attack Note that all of the mechanistic work has been carried out, necessarily, on systems deviating in one aspect or another from the real catalytic one. The outcome depends strongly on the concentration of chloride ions [5],... 

The replacement of the oxygen atom in sulfoxides by nitrogen leads to a new class of chiral sulfur compounds, namely, sulfimides, which recently have attracted considerable attention in connection with the stereochemistry of sulfoxide-sulfimide-sulfoximide conversion reactions and with the steric course of nucleophilic substitution at sulfur. The first examples of chiral sulfimides, 88 and 89, were prepared and resolved into enantiomers by Phillips (127,128) by means of the brucine and cinchonidine salts as early as 1927. In the same way, Kresze and Wustrow (129) were able to separate the enantiomers of other structurally related sulfimides. 

The cyclic form of glucose is termed glucopyra-nose, since the new ring system is a reduced form of the oxygen heterocycle pyran. Nucleophilic attack onto the planar carbonyl may occur from either of its two faces, generating two different stereochemistries at this new chiral centre, designated as a or p. This new chiral centre is termed the anomeric centre. Since there are other chiral centres in the molecule, the mixture of a- and -anomeric forms is not a racemate, but a mixture of diastereoisomers (see Section 3.4.4). The mixture does not contain 50% of each anomer (see below). Although both forms are produced, the form with the equatorial hydroxyl is thermodynamically favoured (see Section 3.3.2). 

The boron-oxygen mesomeric effect described in the previous section explains the lower reactivity of allylic boronates towards carbonyl compounds compared to that of allylic boranes. The use of Lewis acids, however, allows boronate derivatives, including hindered ones, to react at temperatures comparable to the analogous boranes. As described above (see section Mechanism and Stereochemistry ), the most reactive allylic boronates are those with the most electrophilic boron centers.The nucleophilicity of the y-position of an allylic boron reagent (the position that forms the new C-C bond with the aldehyde) is also important to the reactivity of the reagent. For example, allylic boronates with... 

---