Schlosser modification of the Wittig

Retrosynthetic cleavage of the trans A8,9 disubstituted double bond in intermediate 11, the projected precursor of diketone 10, provides phosphorus ylide 12 and aldehyde 13 as potential precursors. In the forward sense, a Wittig reaction could conceivably achieve a convergent coupling of intermediates 12 and 13 with concomitant formation of the requisite trans C8-C9 olefin. Ordinarily, the union of a nonstabilized ylide, such as 12, with an aldehyde would be expected to afford an alkene with a cis geometry.8 Fortunately, however, the Schlosser modification of the Wittig reaction permits the construction of trans olefins from aldehydes and nonstabilized phosphorus ylides.9... 

The normal Wittig reaction of nonstabilized ylides with aldehydes gives Z-olefms. The Schlosser modification of the Wittig reaction of nonstabilized ylides furnishes f-olefins instead. 

The Schlosser Modification of the Wittig Reaction allows the selective formation of -alkenes through the use of excess lithium salts during the addition step of the ylide and subsequent deprotonation/protonation steps. 

The normal preference for (Z) alkenes in reactions of non-stabilized phos-phoranes can be reversed by employing the Schlosser modification of the Wittig reaction (Scheme 6).19 Here, equilibration of the initially formed erythro and threo betaine intermediates is achieved by reaction with additional strong base, usually an alkyl lithium. The resulting betaine ylide then gives the (E) alkene on treatment with a proton source followed by potassium tert-butoxide. 

Although the Schlosser modification of the Wittig reaction provides access to trans-olefins from non-stabilized ylides, the Julia-Lythgoe olefination has proven to be the method of choice for solving this synthetic problem today, a) M. Schlosser, K.-F. Christmann, Justus Liebigs Ann. Chem. 1967, 708, 1-35 b) M. Schlosser, K.-F. Christmann, A, Piskala, Chem. Ber. 1970, 103, 2814-2820. 

Schlosser modification of Wittig reaction The presence of soluble metal salts such as lithium salts decreases the aVfrans-selectivity. The normal Wittig reaction of non-stabilized ylides with aldehydes gives Z-alkenes. The Schlosser modification of the Wittig reaction of non-stabilized ylides furnishes -alkenes. In the presence of lithium halides oxaphosphetanes can often be observed, but betaine-lithium halide adducts are also formed. If lithium salts are added to the equilibrium, oxaphosphetane formation and elimination of... 

Schlosser Modification. Almost pure tran -olefins are obtained from nonstabilized ylides by the Schlosser modification of the Wittig reaction (Wittig-Schlosser reaction). For example, treatment of the (cij )-oxaphosphetane intermediate A with n-BuLi or PhLi at -78 °C results in lithiation of the acidic proton adjacent to phosphoras to produce the P"Oxido phosphonium ylide B. Protonation of B with f-BuOH leads to the trans-1,2-disubstituted alkene C. 

As pointed out in this woric, the mild conditions of the Cr reaction resulted in no observed epimeriza-tion, and offered an excellent alternative to the Schlosser modification of the Wittig reaction. Both the C1CI2 chemistry and the TiCU/Zn method discussed in Section 3.1.12.1.2 have the advantage of preparing the metallocarbene complex in situ. 

Scheme 9.78. Representation of a pathway that accounts for a change in the ratio of (Z)- to fitj-l-phenylpropene by change in the reaction conditions (lower temperature and additional strong base, sometimes called the Schlosser modification of the Wittig reaction). Early phos-phetane fragmentation to alkene is avoided and rotation (or carbanion inversion) to change the isomer ratio is allowed. An excellent discussion of various permutations can be found in Schlosser, M. Strunk, S. Tetrahedron, 1989,45,2649.

The reaction of nonstabilized ylides with aldehydes can be induced to yield trans 3 kenes with high stereoselectivity by a procedure known as the Schlosser modification of the Wittig reaction." In this procedure, the ylide is generated as a lithium halide complex and allowed to react with an aldehyde at low temperature, presumably forming a mixture of diastereomeric betaine-lithium halide complexes. At the temperatures under which the addition is carried out, fragmentation to an alkene and triphenylphosphine oxide does not occur. This complex is then treated... 

This Is a variation of the Schlosser modification of the WIttIg reaction [Schlosser, M, Coffinet, . Synthesis 1971, 380 and Synthesis 1972, 575], Vedejs has published Interesting work that provides a rational for the stereochemical and regloohemical course of the key reaction Vedejs, E. Snoble, K. A. J. "Direct Observation of Oxaphosphatanes from Typical Wittig Reactions" J. Am. Chem. Soc. 1973, 95, 5778,... 

Another synthesis of CJH eminating from the Corey labs involved a modification of the Schlosser modification of the Wittig Reaction. Whereas Wittig reactions between non-stablilized phosphoranes and aldehydes usually provide Z-olefins, Schlosser reported a variation of this reaction that provided -olefins. His group showed that when non-stabilized phosphoranes are reacted with aldehydes in the presence of lithium halides (as opposed to the salt-free conditions that favor Z-olefins), followed by deprotonation of the intermediate adduct, and reprotonation of the resulting j3-oxido ylid, T-olefins are obtained. Corey and Yamamoto reported a variation of this reaction in which the intermediate j3-oxido ylid was treated with formaldehyde, resulting in formation of trisubstituted allylic alcohols. For example, 102 reacted sequentially with aldehyde 103 and formaldehyde to provide 105. This material was then carried on to CJH intermediate 106, and the CJH derivative where R=H. 

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