Stereospecific -Wittig

Stereospecific Wittig rearrangement.1 Wittig rearrangement of the optically active (Z)-allylic ether 1 (9, 475 for a related reaction) gives (R,E)-2 with complete chirality transfer. Rearrangement of (E)-l results in two products, again with complete chirality transfer.1... 

However, stereochemically well-defined acyclic ethers are in demand too, for instance, for the stereospecific Wittig rearrangement. 

The reaction has been extended to include carbanions generated from phosphonates. This is often referred to as the Horner-Wittig or Homer-Emmons reaction. The Horner-Emmons reaction has a number of advantages over the conventional Wittig reaction. It occurs with a wider variety of aldehydes and ketones under relatively mild conditions as a result of the higher nucleophilicity of the phosphonate carbanions. The separation of the olefinic product is easier due to the aqueous solubility of the phosphate by-product, and the phosphonates are readily available from the Arbusov reaction. Furthermore, although the reaction itself is not stereospecific, the majority favor the formation of the trans olefin and many produce the trans isomer as the sole product. 

Potassium Amides. The strong, extremely soluble, stable, and nonnucleophilic potassium amide base (42), potassium hexamethyldisilazane [40949-94-8] (KHMDS), KN [Si(CH2]2, pX = 28, has been developed and commercialized. KHMDS, ideal for regio/stereospecific deprotonation and enolization reactions for less acidic compounds, is available in both THF and toluene solutions. It has demonstrated benefits for reactions involving kinetic enolates (43), alkylation and acylation (44), Wittig reaction (45), epoxidation (46), Ireland-Claison rearrangement (47,48), isomerization (49,50), Darzen reaction (51), Dieckmann condensation (52), cyclization (53), chain and ring expansion (54,55), and elimination (56). 

The dilithio derivative of A-methanesulfinyl-p-toluidine (29) adds to aldehydes and ketones to give, after hydrolysis, the hydroxysulfinamides (30), which, upon heating, undergo stereospecifically syn eliminations to give alkenes. ° The reaction is thus a method for achieving the conversion RR CO — RR C=CH2 and represents an alternative to the Wittig reaction. ... 

The synthesis in Scheme 13.21 starts with a lactone that is available in enantiomer-ically pure form. It was first subjected to an enolate alkylation that was stereocontrolled by the convex shape of the cis ring junction (Step A). A stereospecific Pd-mediated allylic substitution followed by LiAlH4 reduction generated the first key intermediate (Step B). This compound was oxidized with NaI04, converted to the methyl ester, and subjected to a base-catalyzed conjugation. After oxidation of the primary alcohol to an aldehyde, a Wittig-Horner olefination completed the side chain. 

There are two aspects to the stereospecificity of the [1,2]-Wittig rearrangement the steric course (inversion vs. retention) at the migrating carbon atom and at the Li-bearing carbanion center (equation 6). 

In a similar manner, alkynes can undergo sequential carbometallation reactions, previously illustrated in equation (32).136 It is possible to combine carbocupration of alkynes with the use of a Michael acceptor as electrophile when that electrophile is a vinylphosphonium salt, carbocupration can be coupled to Wittig alkenation to result in a stereospecific synthesis of dienes via a one-pot, four-component, four carbon-carbon bond-forming reaction sequence.302... 

Alfytic tertiary amines The reagent serves as a starting material for a regio- and stereospecific synthesis of allylic tertiary amines by the Wittig-Horner reaction shown in the example. 

The Wittig-Still Rearrangement is also a suitable starting point for performing mechanistic studies about the stereospecificity of this process, and Maleczka and Feng have reported on the stereochemical outcome of the [1,2]-Wittig Rearrangement. 

Maleczka, R. E. Geng, F. Stereospecificity of the 1,2-Wittig rearrangement how chelation effects influence stereochemical outcome. 

With regard to the phosphorus stereochemistry, a new stereospecific synthesis of chiral 0,0-dialkyl thiophosphoric acids (6,7) has been developed which is based on the Horner-Wittig reaction of the optically active phosphonothionate carbanions containing the sulfoxide or dithioacetal moieties. The transformation of (R)-(+) 0-methyl 0-isopropyl methanephosphonothionate (10)(8) into (R)-(-) 0-isopropyl phosphorothioic acid (H) best Illustrates this method. 

Many insect pheromones are derivatives of simple alkenes. Disparlure 56, an attractant for the gypsy moth, is an epoxide derived by stereospecific epoxidation from the Z-alkene 57. As neither substituent is anion-stabilising, a simple Wittig should give the right geometry. 

We have a fairly detailed knowledge of the mechanism of the Wittig reaction (Figure 11.3). It starts with a one-step [2+2]-cycloaddition of the ylide to the aldehyde. This leads to a heterocycle called an oxaphosphetane. The oxaphosphetane decomposes in the second step—which is a one-step [2+2]-cycloreversion—to give triphenylphosphine oxide and an alkene. This decomposition takes place stereoselectively (cf. Figure 4.44) a cw-disubstituted oxaphosphetane reacts exclusively to give a cis-alkene, whereas a fraws-disubstituted oxaphosphetane gives only a trans-alkene. The reaction is stereospecific. 

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