Evans’ alkylation

The Evans alkylation method is ideal for this compound.12 The phenylalanine-derived auxiliary 87 is acylated to make the starting material 99. The sodium enolate is alkylated with /-Hu bromoacetate to give 100 with the expected stereoselectivity. Exo-cleavage gives 101 that has one free C02H group and one protected as a f-Bu ester. This was used to make 98. 

A novel approach has been developed towards the total synthesis of (+ )-allopumiliotoxin 339A (112), a minor consituent of skin extracts from the family of Panamanian poison frogs Dendrobates auratus, based on an intramolecular chromium(II)-mediated cyclization. Ketone 107, after a Homer—Emmons condensation, DIBAL reduction, and conversion to the bromide 109, is homologated based on Evans alkylation procedure [45] and transformed through a series of efficient reactions into the iodoolefin 110. 

In addition, under the help of a chiral auxiliary group, the generated enolate can also react with electrophiles to form of-alkylated ketones," and this specific reaction is called Evans alkylation " (such as in the case for the preparation of discodermolide ). 

Cylindrocyclophane A [85] In 20(X), Smith and coworkers achieved the total synthesis of cylindrocyclophanes A (123) and F (124). Their strategy relied on a dimerization by metathesis (Scheme 2.67) [85], This family of natural products presents an unusual 22-membered [7,7]-paracyclophane structure. Concerning the synthesis of cylindrocyclophane A, two stereogenic centers are controlled by a Myers alkylation, while the monomer (125) is obtained from three different fragments, namely, the product of the Myers alkylation 126, cyclobutenone 127, and the silylated ynol 128 bearing a stereogenic center controlled by an Evans alkylation. 

Scheme 2.84) revolved around an intramolecular nickel-catalyzed reductive alkyne-aldehyde coupling to generate the macrolactone core, an intermolecular nickel-catalyzed reductive alkyne-epoxide coupling to access the C13-C18 fragment of the molecule, and an Evans alkylation to control the stereogenic center at C14. 

The synthesis of aldehyde 212 started with an Evans alkylation of the known acylated oxazolidinone 215 with allyl iodide 216 to form the corresponding alkylated product 217 as a single diastereoisomer in 81% yield (Scheme 2.88) [118]. Reductive removal of the chiral auxiliary followed by tosylation of the resulting primary alcohol, cyanide substitution, and reduction with DIBAL... 

Crimmins et al. further expanded the utility of the Evans alkylation procedure to include hydroxyl-protected a-hydroxy carboxylic acids (Table 7.4). The derived N-acyl oxazolidinones were deprotonated with NaHMDS to... 

Our studies also included IR spectroscopic investigation of the observed ions (Fig. 6.2). John Evans, who was at the time a spectroscopist at the Midland Dow laboratories, offered his cooperation and was able to obtain and analyze the vibrational spectra of our alkyl cations. It is rewarding that, some 30 years later, FT-IR spectra obtained by Denis Sunko and his colleagues in Zagreb with low-temperature matrix-deposition techniques and Schleyer s calculations of the spectra showed good agreement with our early work, considering that our work was... 

Ketones, in which one alkyl group R is sterically demanding, only give the trans-enolate on deprotonation with LDA at —12°C (W.A. Kleschick, 1977, see p. 60f.). Ketones also enolize regioseiectively towards the less substituted carbon, and stereoselectively to the trans-enolate, if the enolates are formed by a bulky base and trapped with dialkyl boron triflates, R2BOSO2CF3, at low temperatures (D A. Evans, 1979). Both types of trans-enolates can be applied in stereoselective aldol reactions (see p. 60f.). 

Chiral oxazolines were the first ehiral auxiliaries used for asymmetrie enolate alkylations. Subsequent studies led to the development of a number of other ehiral auxiliaries (34-38) ineluding those reported by Evans, Myers, Enders, Sehollkopf, and others, whieh are now widely used in asymmetrie synthesis. Although these new auxiliaries frequently provide higher yields and enantioseleetivities than the oxazolines originally developed by Meyers, the pioneering work of Meyers laid the groundwork for these later studies. 

This highly convergent synthesis amply demonstrates the utility of Evans s asymmetric aldol and alkylation methodology for the synthesis of polypropionate-derived natural products. By virtue of the molecular complexity and pronounced lability of cytovaricin, this synthesis ranks among the most outstanding synthetic achievements in the macrolide field. 

Sn -I- 2RI R2Snl2 (where R is the alkyl group and I is the anion). Methyltin stabilizers are produced by direct synthesis in the United States. Dibutyltin dichloride is manufactured from crude tetrabutyltin and tin tetrachloride and is usually catalysed with aluminium trichloride (Blunden Evans, 1989 Gaver, 1997 Thoonen et al, 2001). 

During the course of the development of our group s alkylation/reductive decyanation strategy, a very reliable method for distinguishing between syn-and anfz-l,3-diols was discovered [17,18]. The acetonide methyl groups reliably display diagnostic C-NMR chemical shifts, allowing for stereochemistry to be determined simply by inspection (Fig. 1). Evans later extended the C-NMR chemical correlation to polypropionate chains [19,20]. 

The degradation of alkyl benzenes (Hutchins 1991 Evans et al. 1991a,b Altenschmidt and Fuchs 1991). In these studies, some of the organisms referred to the genus Pseudomonas have been transferred to the genus Thauera (Anders et al. 1995). 

An allylic sulfenate, like 199, is known to be in equilibrium with allylic sulfoxide, like 196, although its concentration is usually low . Various allylic sulfoxides can be prepared by treatment of allylic alcohols with arenesulfenyl chlorides . Evans and coworkers prepared various allylic alcohols by treating the corresponding allylic sulfoxides with trimethyl phosphite. For example, the carbanion from a cycloalkenyl sulfoxide 201 was readily alkylated at the a-position by treatment with alkyl halide. The resulting alkylated derivative 202 was then treated with trimethyl phosphite and 3-substituted cycloalkenol was obtained. Alkylation of acyclic allylic sulfoxide 204 gave... 

Another approach in the use of chiral S/P ligands for the hydrosilylation reaction of ketones was proposed more recently by Evans et Thus, in 2003, these workers studied the application of new chiral thioether-phosphinite ligands to enantioselective rhodium-catalysed ketone hydrosilylation processes. For a wide variety of ketones, such as acyclic aryl alkyl and dialkyl ketones as well as cyclic aryl alkyl ketones and also cyclic keto esters, the reaction gave high levels of enantioselectivity of up to 99% ee (Scheme 10.44). 

Evans and Takacs23 demonstrated a diastereoselective alkylation based on metal ion chelation of a lithium enolate derived from a prolinol-type chiral auxiliary. This method can provide effective syntheses of a-substituted carbox-... 

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