Download Wittig Alkene Synthesis: Regioselective Alkene Preparation from Aldehydes and Ketones and more Study notes Chemistry in PDF only on Docsity! 19.13 THE WITTIG ALKENE SYNTHESIS 933 PROBLEMS 19.32 Draw the structures of all aldehydes or ketones that could in principle give the following product after application of either the Wolff–Kishner or Clemmensen reduction. 19.33 Outline a synthesis of 1,4-dimethoxy-2-propylbenzene from hydroquinone (p-hydroxyphenol) and any other reagents. 19.13 THE WITTIG ALKENE SYNTHESIS Our tour through aldehyde and ketone chemistry started with simple additions; then addition followed by substitution (acetal formation); then additions followed by elimination (imine and enamine formation). Another addition–elimination reaction, called the Wittig alkene synthe- sis, is an important method for preparing alkenes from aldehydes and ketones. An example of the Wittig alkene synthesis is the preparation of methylenecyclohexane from cyclohexanone. The Wittig synthesis is especially important because it gives alkenes in which the position of the double bond is unambiguous; in other words, the Wittig synthesis is completely regios- elective. It can be used for the preparation of alkenes that would be difficult to prepare by other reactions. For example, methylenecyclohexane, which is readily prepared by the Wittig synthesis (Eq. 19.70), cannot be prepared by dehydration of 1-methylcyclohexanol; 1- methylcyclohexene is obtained instead, because alcohol dehydration gives the alkene iso- mer(s) in which the double bond has the greatest number of alkyl substituents (Sec. 10.1). The nucleophile in the Wittig alkene synthesis is a type of ylid. An ylid (sometimes spelled ylide) is any compound with opposite charges on adjacent, covalently bound atoms, each of which has an electronic octet. (19.71) 1-methylcyclohexene methylenecyclohexane H2O H2SO4 H2SO4 CH3L CH2 (little or none formed) + A CH3 OH"" (19.70)+ methylenecyclohexane triphenylphosphine oxide an ylid CH23_ PPh3 |L CH2A cyclohexanone O11A + Ph3P | _LO 311 LH3C LCH2CH(CH3)2 19_BRCLoudon_pgs5-0.qxd 12/9/08 11:41 AM Page 933 934 CHAPTER 19 • THE CHEMISTRY OF ALDEHYDES AND KETONES. CARBONYL-ADDITION REACTIONS Because phosphorus, like sulfur (Sec. 10.9), can accommodate more than eight valence elec- trons, a phosphorus ylid has an uncharged resonance structure. Although the structures of phosphorus ylids are sometimes written with phosphorus– carbon double bonds, the charged structures, in which each atom has an octet of electrons, are very important contributors. The mechanism of the Wittig alkene synthesis, like the mechanisms of other carbonyl reactions, involves the reaction of a nucleophile at the carbonyl carbon. The nucleophile in the Wittig synthesis is the anionic carbon of the ylid. The anionic oxygen in the resulting species re- acts with phosphorus to form an oxaphosphetane intermediate. (An oxaphosphetane is a satu- rated four-membered ring containing both oxygen and phosphorus as ring atoms.) Under the usual reaction conditions, the oxaphosphetane spontaneously undergoes a b-elimi- nation to give the alkene and the by-product triphenylphosphine oxide. The ylid starting material in the Wittig synthesis is prepared by the reaction of an alkyl halide with triphenylphosphine (Ph3P) in an SN2 reaction to give a phosphonium salt. The phosphonium salt can be converted into its conjugate base, the ylid, by reaction with a strong base such as an organolithium reagent. (19.74a)Ph3P3 + H3CL 311Br benzene 2 days triphenylphosphine methyl bromide methyltriphenylphosphonium bromide (a phosphonium salt; 99% yield) Ph3P CH3L| _3 311Br (19.73b) triphenylphosphine oxide the alkene product C% % PPh3 O 31+ S oxaphosphetane PPh3 L L C" " "% O 31 H2C CH2 (19.73a)CAO1$ ) PPh3L| an oxaphosphetane an ylid 3 H2C PPh3 _ | L L C" "% O 311 H2C PPh3 L L C" " "% O 31 H2C .. (19.72)Ph3PLCH22_| Ph3P CH2 phosphorus shares 10 electrons A an ylid each charged atom has a complete octet P| Ph CH2Ph Ph L L" " 2_ 19_BRCLoudon_pgs5-0.qxd 12/9/08 11:41 AM Page 934
