Olefination reactions Peterson reaction

Peterson Olefination Reaction (Peterson Elimination, Silyl-Wittig Reaction) The Reaction ... 

The phosphorus ylides of the Wittig reaction can be replaced by trimethylsilylmethyl-carbanions (Peterson reaction). These silylated carbanions add to carbonyl groups and can easily be eliminated with base to give olefins. The only by-products are volatile silanols. They are more easily removed than the phosphine oxides or phosphates of the more conventional Wittig or Homer reactions (D.J. Peterson, 1968). 

The Peterson reaction has two more advantages over the Wittig reaction 1. it is sometimes less vulnerable to sterical hindrance, and 2. groups, which are susceptible to nucleophilic substitution, are not attacked by silylated carbanions. The introduction of a methylene group into a sterically hindered ketone (R.K. Boeckman, Jr., 1973) and the syntheses of olefins with sulfur, selenium, silicon, or tin substituents (D. Seebach, 1973 B.T. Grdbel, 1974, 1977) illustrate useful applications. The reaction is, however, more limited and time consuming than the Wittig reaction, since metallated silicon derivatives are difficult to synthesize and their reactions are rarely stereoselective (T.H. Chan, 1974 ... 

Another method that has been used to prepare phosphaalkenes is the phos-pha-Peterson reaction, a phosphorus analog of the Peterson olefination [46-49]. In this reaction a lithium silylphosphide is treated with an aldehyde or ketone to yield the phosphaalkene (9). Analogous reactions can be conducted with bis(trimethylsilyl)phosphines (10) and ketones (11) using a catalytic quantity of anhydrous base (i.e., NaOH, KOH) [50]. Generally, the reactions proceed cleanly and in high yield. Sufficiently bulky substituents must be employed to stabilize the P=C bond and prevent rapid dimerization to 1,3-diphosphetaines. 

This section deals with reactions that correspond to Pathway C, defined earlier (p. 64), that lead to formation of alkenes. The reactions discussed include those of phosphorus-stabilized nucleophiles (Wittig and related reactions), a a-silyl (Peterson reaction) and a-sulfonyl (Julia olefination) with aldehydes and ketones. These important rections can be used to convert a carbonyl group to an alkene by reaction with a carbon nucleophile. In each case, the addition step is followed by an elimination. 

Scheme 2.19 provides some examples of the Peterson olefination. The Peterson olefination has not been used as widely in synthesis as the Wittig and Wadsworth-Emmons reactions, but it has been used advantageously in the preparation of relatively... 

Chapters 1 and 2 focus on enolates and other carbon nucleophiles in synthesis. Chapter 1 discusses enolate formation and alkylation. Chapter 2 broadens the discussion to other carbon nucleophiles in the context of the generalized aldol reaction, which includes the Wittig, Peterson, and Julia olefination reactions. The chapter and considers the stereochemistry of the aldol reaction in some detail, including the use of chiral auxiliaries and enantioselective catalysts. 

This process has also been extended to include the Peterson olefination reaction (eq 5) of 12 (where E = Me3Si) to give a series of substituted vinyl derivatives 13. Both 12 and 13 have typically been obtained in high yield and have been fully characterized by NMR spectroscopy and elemental analysis. 

The Peterson olefination reaction involves the addition of an a-silyl substituted anion to an aldehyde or a ketone followed by the elimination of silylcarbinol either under acidic (awP -elimination) or basic (syn-elimination) conditions to furnish olefins178. Thus, Peterson olefination, just like Wittig and related reactions, is a method for regioselective conversion of a carbonyl compound to an olefin. Dienes and polyenes can be generated when the Peterson reaction is conducted using either an ,/l-unsaturated carbonyl compound or unsaturated silyl derivatives as reaction partners (Table 20)179. 

The spirocompounds 34 (M = Ti or Zr) have been prepared . Studies of the thermolysis of pentacoordinate 1,2-oxasiletanides 35, potential intermediates in both the Peterson reaction and the homo-Brook rearrangement of p-hydroxyalkylsilanes with bases, in the presence of a proton source afforded the olefin, RCH=C(CF3)2 and/or the alcohol, (CF3)2CHOH <99CL1139>. 

These P elimination reactions have been used in an olefine synthesis called the Peterson olefination reaction which is analogous (and sometimes superior) to the Wittig reaction. The Peterson olefination reaction involves the addition of an a-silyl carbanion to an aldehyde or ketone to give P-hydroxysilane, followed by P-elimination to give the olefine. 

Alai/r[(Z)-CF=C]-Pro containing N, 0-diacylhydroxamic acid type protease inhibitors have been prepared as shown in Scheme 18 [63,64], The synthesis is based upon the use of fert-butyl-a-fluoro-trimethylsilylacetate in a variation of the Peterson olefination procedure to construct the necessary functionalized fluoroolefin. Treatment of 51 with 4 equiv. of lithium diisopropylamide (LDA) and 6equiv. of chlorotri-methylsilane at 78°C formed 52 in 71% yield. The key step is the Peterson olefination reaction of the TBDMS-protected 2-(hydroxymethyl)cyclopentanone (53) with tert-butyl-a-fluoro-a-trimethylsilylacetate (52). The fluoroolefin product was obtained as a mixture of (Z) (E) isomers (54). Separation of the double-bond isomers by column chromatography provided (Z) isomer (54) in 43% yield. Further... 

Magnesium, 235 Samarium(II) iodide, 270 Titanium(IV) chloride, 304 Addition reactions to carbonyl groups—Addition of functionalized CARBON NUCLEOPHILES (see also Aldol reaction and other specific condensation reactions, Meth-ylenation, Peterson Olefination, Refor-matsky reaction, Wittig reaction, Wittig-Horner reaction)... 

However, the reaction of benzaldehyde with bis(trimethylsilyl)methyllithium gave a mixture of trans and cis isomers in a ratio of 1.4 1 (equation 128). If this reaction involved the /J-oxidosilane intermediate 158, the same stereochemical outcome would be expected. This was taken to suggest that, in this particular Peterson olefination reaction at least, the /J-oxidosilane 158 is not a major intermediate, and that the oxasiletane anion is formed directly by simultaneous formation of C—C and Si—O bonds. 

The stereochemical outcome of the Peterson reaction between unsymmetrically substituted a-silyl carbanions and aldehydes or unsymmetrical ketones is determined by the relative rates of formation of the threo and erythro /3-oxidosilancs. Often the rates are similar, to give a product alkene E Z ratio of 1 1, although some workers report a predominance of cis olefins in the reactions of aldehydes. 

A relatively new synthetic approach to silenes was established independently in the laboratories of Oehme101-110, Apeloig39,111 and Ishikawa112,113. The key-step is a base-initiated 1,2-elimination of silanolate from at-hydroxydi si lanes 157 and formation of silenes 158 analogous to the original Peterson olefination reaction (equation 39). 

Carbonyl olefination.1 The reaction of 1 with benzaldehyde results in a 1 1 separable mixture of the threo- and eryfAro-adducts (2a and 2b, respectively). The adducts undergo stereospecific ypn-elimination when heated to give /i-phenyl-thiostyrene (3). The (E)-isomer (3a) is formed from 2a, and the (Z)-isomer (3b) is formed from 2b. On the other hand, anfr -elimination obtains on treatment of 2 with perchloric acid in methanol. This carbonyl olefination has one advantage over the Peterson reaction in that intermediate adducts can be isolated and converted as desired to an (E)- or a (Z)-olefin. 

A general approach to precursors of p-quinonemethides has been developed that involved the olefinations of p-quinoneketals as 615 with suitable nucleophiles. For example, the reaction of 615 with the anion derived from 613 led directly to the p-quinonemethide ketal 616 via a Peterson reaction (Scheme 57) (225). Alternatively, 616 was prepared by the initial reaction of 615 with the anion of 614 followed by mild dehydration of the intermediate tertiary alcohol... 

The Peterson Reaction allows the preparation of alkenes from a-silylcarbanions. The intermediate p-hydroxy silane may be isolated, and the elimination step - the Peterson Elimination - can be performed later. As the outcome of acid or base-induced elimination is different, the Peterson Olefination offers the possibility of improving the yield of the desired alkene stereoisomer by careful separation of the two diastereomeric p-hydroxy silanes and subsequently performing two different eliminations. 

Wittig olefination reaction ( the phosphorus way ) has been a very popular reaction in organic synthesis. However, it is now in competition with Peterson/Chan olefination reaction327 ( the silicon way ). Formally, this latter involves the formation of a (3-silyl heteroatomic anion, which in the absence of an electrophile undergoes a (3-shift of the silyl moiety to the heteroatom (usually oxygen) with final elimination of silylated heteroatomic anion and formation of the olefin. 

Peterson olefination reaction has been utilized to create a new access to dihydroiso-quinoline derivatives.95,136 137... 

Intermediacy of pentacoordinate oxasiletanides in the Peterson olefination reaction has been discussed <2002CSR195, B-2004MI18>. Products of thermolysis of 1,2-oxasiletanides indicate that they are the intermediates of both Peterson and homo-Brook reactions <1999CL1139, 2003BCJ471>. 

Among such migrations, the Peterson reactions to give olefins have been shown to proceed via intramolecular 1,3-silyl migrations from C to O (equation 129). 

A method that makes available aromatic and aliphatic aldehyde derived sulfin-imines 47, for the first time, was recently introduced by Davis and co-workers.23,36 This one-pot procedure entails treatment of the Andersen reagent 40 with LiHMDS to generate 44 which subsequently reacts with the lithium methoxide by-product to produce silyl sulfinamide anion 46. Reaction of 46 with the aldehyde in a Peterson-type olefination reaction affords the sulfinimine 47 in >96% ee. This method was highly effective for the preparation of arylidene sulfmamides 47 (R = aryl) which were usually obtained in 60-76% yield although the alkyl counterparts... 

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