SAE reaction

The examples addressed thus far adequately convey the utility of the SAE reaction as a tool for the reagent-control strategy. Nonetheless, the power of the SAE reaction and the capabilities of the new reagent-control strategy are demonstrated even more forcefully in the total synthesis of all eight L-hexoses (compounds 1-8) by the groups of Masamune and Sharpless.11 The remainder of this chapter is devoted to this elegant joint venture. 

The emergence of the powerful Sharpless asymmetric epoxida-tion (SAE) reaction in the 1980s has stimulated major advances in both academic and industrial organic synthesis.14 Through the action of an enantiomerically pure titanium/tartrate complex, a myriad of achiral and chiral allylic alcohols can be epoxidized with exceptional stereoselectivities (see Chapter 19 for a more detailed discussion). Interest in the SAE as a tool for industrial organic synthesis grew substantially after Sharpless et al. discovered that the asymmetric epoxidation process can be conducted with catalytic amounts of the enantiomerically pure titanium/tartrate complex simply by adding molecular sieves to the epoxidation reaction mix-... 

The construction of key intermediate 18 can be conducted along similar lines. Sharpless asymmetric epoxidation of allylic alcohol 22 using (+)-DET furnishes epoxy alcohol 52b (Scheme 11). Subjection of the latter substance to the same six-step reaction sequence as that leading to 54a provides allylic alcohol 54b and sets the stage for a second SAE reaction. With (+)-DET as the... 

SAE reaction see Sharpless asymmetric epoxidation Saegusa oxidation 390 samarium diiodide 496, 633, 638 saponification 49, 207 sativene 382 f. 

Just as in phenyl halides, the halogen can be replaced by hydrogen, by a metal, or be coupled. Two of the four mechanisms of such nucleophilic substitutions are also familiar from benzene chemistry via arynes and by the SRN1 mechanism. However, of the two further mechanisms of nucleophilic replacement, the ANRORC is unique to heterocycles, and SAE reactions occur only with strongly activated benzenoid systems. 

The Shaipless asymmetric epoxidation reaction is often used as a key step in synthetic protocols involving the synthesis of natural products such as terpenes, carbohydrates, insect pheromones, and pharmaceutical products. The SAE reaction is characterized by its simplicity and reliability. The epoxides are obtained with predictable absolute configuration and in high enantiomeric excess (ee). Moreover, 2,3-epoxy alcohols serve as versatile intermediates for a host of stereospecific transformations. 

Diastereoselectivity In applying the reagent-control strategy to SAE reactions, consider the following reported experiments ... 

The utility of the SAE reaction stems from the fact that chiral epoxy alcohols possess reactive sites at C(l), C(2), and C(3) that can be transformed into a large number of other functionalities while maintaining their preexisting chiral centers. Moreover, either of the two enantiomers may be obtained. 

Resolution of Racemic Mixtures ofAllylic Alcohols.An important application of the SAE reaction is the kinetic resolution of racemic mixtures of secondary allylic alcohols. In this case, the chiral catalyst reacts faster with one enantiomer than with the other since the two transition states are diastereomeric. Thus, using 0.5 mole of r-BuOOH for each mole of racemic allylic alcohol, the faster-reacting enantiomer will consume the r-BuOOH to furnish the epoxide. This leaves behind the unreacted slower-reacting allylic alcohol in high enantiomeric excess, which is then separated from the epoxide via chromatography. 

M. Luoma, P. Lappi, and R. Lylykangas, Evaluation of High Cell Density E-Flow Catalyst, SAE 930940, Society of Automotive Engineers, Warrendale, Pa., 1993. Good reference for mass-transfer limited model reactions. 

In light of the previous discussions, it would be instructive to compare the behavior of enantiomerically pure allylic alcohol 12 in epoxidation reactions without and with the asymmetric titanium-tartrate catalyst (see Scheme 2). When 12 is exposed to the combined action of titanium tetraisopropoxide and tert-butyl hydroperoxide in the absence of the enantiomerically pure tartrate ligand, a 2.3 1 mixture of a- and /(-epoxy alcohol diastereoisomers is produced in favor of a-13. This ratio reflects the inherent diasteieo-facial preference of 12 (substrate-control) for a-attack. In a different experiment, it was found that SAE of achiral allylic alcohol 15 with the (+)-diethyl tartrate [(+)-DET] ligand produces a 99 1 mixture of /(- and a-epoxy alcohol enantiomers in favor of / -16 (98% ee). 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

The development of Sharpless asymmetric epoxidation (SAE) of allylic alcohols in 1980 constitutes a breakthrough in asymmetric synthesis, and to date this method remains the most widely applied asymmetric epoxidation technique [34, 44]. A wide range of substrates can be used in the reaction ( ) -allylic alcohols generally give high enantioselectivity, whereas the reaction is more substrate-dependent with (Z)-allylic alcohols [34]. 

In our work with aminolysis of vinylepoxides (see Section 9.2.1.1), the substrates were routinely synthesized by SAE followed by Swern/Wittig reactions (Table 9.3, Entries 1-4) [48, 49]. This procedure is well suited for terminal olefins, but dis-ubstituted olefins can seldom be obtained with useful (E Z) selectivities. Nakata recently synthesized some advanced intermediates towards natural products in this manner (Entries 5, 6) [50, 51]. 

Lll soot images indicating soot formation in the reacting jet and increased concentration downstream from the standing premixed reaction zone. (From Dec, J.E., SAE Trans., 106, 1319, 1997. With permission.)... 

Subacute AIDS encephalitis (K3) was detected in adult and pediatric brains. Immunocytochemical analysis of adult and pediatric brains revealed gp 41 im-munoreactivity (78% and 40% respectively). Virtually all adult brains with SAE had gp 41 immunoreactivity in macrophages and microglia. Spinal cords with vacuolar myelopathy or corticospinal tract degeneration had only rare gp 41 positive cells. Brains of aborted fetuses from HIV-1 seropositive women were negative for gp 41 immunocreactivity, but some were positive for HIV-1 by polymerase chain reaction. 

Scheme 8 summarizes the introduction of the missing carbon atoms and the diastereoselective epoxidation of the C /C double bond using a Sharpless asymmetric epoxidation (SAE) of the allylic alcohol 64. The primary alcohol 62 was converted into the aldehyde 63 which served as the starting material for a Horner-Wadsworth-Emmons (HWE) reaction to afford an E-configured tri-substituted double bond. The next steps introduced the sulfone moiety via a Mukaiyama redox condensation and a subsequent sulfide to sulfone oxidation. The sequence toward the allylic alcohol 64 was com-... 

This section summarizes the advances in the description of flow, transport and reaction phenomena in the filter wall scale. The filter wall scale is the one which triggers the material development in the field new filter structures, multifunctional catalyst coatings and ash interactions (SAE International,... 

Konstandopoulos, A. G., Lorentzou, S., and Kostoglou, M. Wall scale reaction models in diesel particulate filters. SAE Technical Paper No. 2007-1-1130 (2007). 

The relative reactivities with respect to nucleophilic SAE displacement increase in the order Cl < Br < I < F. The relative reactivities of nucleophiles are illustrated by the reactions of 2-bromopyridine replacement by the following groups occurs under the conditions given (an indicates that the product spontaneously tautomerizes) ... 

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