Inversion with oxygen nucleophiles

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. 

Finally, (i )-malates are available from L-malic acid derivatives by inversion reactions of the 2-hydroxyl group with oxygen nucleophiles (see Section 3.2.2.1). 

The intervention of one mole of nucleophile in the inversion process contrasts with the results obtained for racemization of chlorosilane where two moles of nucleophiles are involved (13). To account for their results, Martin and Stevenson proposed that inversion at tetracoordinate silicon arises from an isomerization of a pentacoordinated intermediate via Berry pseudorotation steps. Several pathways were proposed, the most interesting being a nucleophilic attack at a carbon-oxygen edge of the tetrahedral silicon compound. In the resulting intermediate, a single Berry pseudorotation with the nucleophile as pivot and equatorial departure of the nucleophile causes an inversion at silicon (eq. [110]). A... 

Reaction of this protonatod molecule with a nucleophile will therefore occur at the. 3 carbon, which is the tnost carbocationlike, as you would expect for an SnI reaction. However, because of the position of the oxygen leaving group, which is at least partially bonded to the 3 carbon, the nucleophile can attach to the 3 carbon only from the side opposite the oxygen, resulting in inversion at that carbon atom, its you would expect fur tin S, <2 reaction (sec iliustrution above), l-or these reasons, the, SnI and, Sn2 labels really don t apply in a clear-cut w.ay . SnI considerations dciermine which C-O bond breaks, but the direction of approach of the nucleophile is chanictcristic of an Sn2 process. 

Crown-catalysed substitution by chromate ions provides a direct oxidation route from primary halides to aldehydes via chromate esters (39). Superoxide anion becomes a useful new type of oxygen nucleophile now that potassium superoxide can be solubilized with 18-crown-6 and derivatives. Alkyl halides or sulphonates (RX) may be converted to alcohols or dialkyl peroxides, depending on the exact conditions, through an initial nucleophilic substitution with inversion (Scheme 8). 

Reaction with Phenols and Other Oxygen Nucleophiles. When alcohols react with phenols, DEAD, and TPP, the corresponding aryl alkyl ethers are produced. A tertiary amine may facilitate the reaction. In general, the reaction proceeds with clean inversion of chiral secondary carbinol centers (eq 2 AH = a phenol). Depending on the structure of the substrate, al-lylic rearrangement and neighboring group participation can... 

The usual oxidizing agents transfer oxygen (or halogens and related species with subsequent hydrolysis) stepwise to the sulfur of thioethers Rates of step A compared with those of step B are faster with electrophilic oxidation agents (peroxy acids) inversely, rates of step B compared with those of step A are faster with nucleophilic oxidation agents (peroxy anions)339-341. 

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