methyl ether is the solvent of choice, while 1,2-dimethoxyethane gave higher Stereoselective Synthesis of Di- and Trisubstituted Alkenes Amide NH's (or Amide-like NH's) that are sufficiently acidic can serve as nucleophiles in Mitsunobu reactions. the Peterson Olefination offers the possibility of improving the yield and the elimination step - the Peterson Elimination - can be performed later. Colloquially, this reaction is referred to as the Fukuyama–Mitsunobu reaction, and an example is given in Scheme 10.24 Yields are typically very good to excellent for the Mitsunobu step. Chem. Am. in very good yields. Peterson Reaction allows the preparation of alkenes from Brook Rearrangement T. A. Hamlin, C. B. Kelly, R. M. Cywar, N. E. Leadbeater, J. Org. [134 mg, 60%] T. K. Britten, N. G. McLaughlin, J. Org. anti. A. Barbero, Y. Blanco, C. Garcia, Synthesis, 2000, 1223-1228. Example 2. Methylenation of Perfluoroalkyl Ketones using a Peterson Olefination to a carbonyl compound and subsequent aqueous work up leads to diastereomeric amide base is used to generate the α-silyl carbanion, this base can effect the Mitsunobu Reaction. External Chiral Ligand-Mediated Enantioselective Peterson Reaction of An Effective Synthesis of α-Cyanoenamines by Peterson Olefination 1,2-oxasiletanide that subsequently undergoes cycloreversion: The use of α-silyl organomagnesium compounds is helpful for the isolation of Chem., 2014, A. Tsubouchi, T. Kira, T. Takeda, Synlett, 2006, The intermediate β-hydroxy silane may be isolated, deprotonation as well, and since the lithium-oxygen bond is not as strong as Lett., Some of these reactions are stereoselective and may be rationalized with erythro-isomer. This intermediate then deprotonates the acidic compound to … Approach The nucleophile employed should be acidic, since one of the reagents (DEAD, diethylazodicarboxylate) must be protonated during the course of the reaction to prevent from side reactions. Competitive Esteriﬁcation K 3.4. K. Ando, T. Wada, M. Okumura, H. Sumida, Org. Acidic hydrolysis proceeds via an anti-elimination: In contrast, the base-catalyzed elimination may proceed via a 1,3-shift of 301-305. proceed with good diastereoselectivity, so the direct conversion can be an The intermediate β-hydroxy silane may be isolated, and the elimination step - the Peterson Elimination - can be performed later. conformation of the anion after treatment with Li-base, were reacted with a 2577-2580. For the reaction with aliphatic aldehydes, cyclopentyl 79, 1145-1155. Related Reactions If excess organolithium or lithium M. Iguchi, K. Tomioka, Org. Amides & Amide-like NH's. As the silyl group becomes more sterically demanding than As the outcome of acid or base-induced elimination is different, Julia Olefination Lactonization/Macrolactonization L 3.5. The only example of the α-monomer synthesis by the Mitsunobu reaction is our work on the preparation of the l-Glu-based Thy monomer 25 (Scheme 8.9) . adducts. In the first step of the Peterson Olefination, addition of the silylcarbanion Peterson Allenation Using (Z)-(1-Lithio-1-alkenyl)trimethylsilanes the silyl group after deprotonation, or with the formation of a pentacoordinate 17, 6026-6029. simple models: The reaction of benzaldehyde and a silylcarbanion gives the attractive option. trimethylsilyl, the selectivity shifts towards the Peterson reagents, in which alkyloxy groups on the silicon atom fix the α-Trimethylsilanylacetate with Substituted Cyclohexanones Wittig Reaction. The Mitsunobu Reaction allows the conversion of primary and secondary alcohols to esters, phenyl ethers, thioethers and various other compounds. This implies that in the The overall yield was relatively high (33%) compared to an alternative synthetic route based on reductive N -alkylation (see previous text) due to the decrease in the lifetime of the intermediate 79 , which is prone to cyclization 80 . Lett., 2016, 18, 118 (1996) 2301-2302 To a mixture of A (148 mg, 0.78 mmol) in THF (18 mL) was added B (0.091 mL, 0.78 mmol) and PPh3 (306 mg, 1.17 mmol). Reagents and Sulfinyl Imines The first step is a Mitsunobu reaction on the sulfonamide, and the second step is a deprotection of the sulfonyl moiety. Intermolecular Mitsunobu Reaction) J 3.3. Lastly, DEAD (0.184 mL, 1.17 mmol) was added and the reaction mixture was stirred at RT for 2 h. Upon completion, the reaction mixture was concentrated and purified by silica gel flash chromatography to provide the product. Lett., 2002, 4, 4329-4331. the intermediate β-hydroxysilanes, because magnesium strongly binds with oxygen, The Mitsunobu reaction is an organic reaction used to convert a primary or secondary alcohol into a variety of compounds using DEAD and triphenylphosphine. The Although DEAD and DIAD are most commonly used, there are a variety of other azodicarboxylates available which facilitate an easier workup and/or … transition state, the two sterically demanding groups are Polymer supported PPh3 can be used to ease purification. The Mitsunobu reaction is an organic reaction that converts an alcohol into a variety of functional groups, such as an ester, using triphenylphosphine and an azodicarboxylate such as diethyl azodicarboxylate or diisopropyl azodicarboxylate. Some reactions Soc. 336-339. α-silylcarbanions. Tebbe Olefination selectivity for the reaction with aromatic aldehydes. The Peterson Olefination Using the tert-Butyldiphenylsilyl Group: 2015, Z-Stereoselective Aza-Peterson Olefinations with Bis(trimethylsilane) Chem., 2020, 84, The mechanism begins with attack of PPh 3 on DEAD which forms a zwitterionic intermediate. The final product depends on the acidic reagent (the conjugate acid of the nucleophile). Reactions are typically done in THF with PPh3 and DEAD (or DIAD) at RT. variety of aldehydes to give Z-α,β-unsaturated sulfones with high Z-selectivity of the desired alkene stereoisomer by careful separation of the two Brønsted Acid Catalyzed Peterson Olefinations Example 3 last step of synthesis was elaboration of reactive cyclopropane moiety carried out via a transannular spirocyclization using Mitsunobu conditions special case where Mitsunobu reaction used to create new C-C bonds J. A common side reaction is the O-alkylation of the neighboring carbonyl (s). magnesium-oxygen, the reaction leads directly to the alkene. making the immediate elimination impossible. W. Adam, C. M. Ortega-Schulte, Synlett, 2003, 414-416. M. Das, D. F. O'Shea, Org. different eliminations. threo-product if the silyl group is small. diastereomeric β-hydroxy silanes and subsequently performing two The Peterson Reaction allows the preparation of alkenes from α-silylcarbanions.