Peterson olefination,

The Peterson olefination can be viewed as a silicon variant of the Wittig reaction, the well-known method for the formation of carbon-carbon double bonds. A ketone or aldehyde 1 can react with an a-silyl organometallic compound 2—e.g. with M = Li or Mg—to yield an alkene 3. 

The Peterson olefination is a quite modern method in organic synthesis its mechanism is still not completely understood. The a-silyl organometallic reagent 2 reacts with the carbonyl substrate 1 by formation of a carbon-carbon single bond to give the diastereomeric alkoxides 4a and 4b upon hydrolysis the latter are converted into /3-hydroxysilanes 5a and 5b  

By application of the most common procedure—i.e by using an a-silylated organolithium or magnesium reagent—the /3-hydroxysilane 5a/5b can be isolated. However in the case of M = Na or K, the alkoxide oxygen in 4a/4b is of strong ionic character, and a spontaneous elimination step follows to yield directly the alkene 3. 

The next step of the Peterson olefination allows for the control of the E Z-ratio of the alkene to be formed by proper choice of the reaction conditions. Treatment of /3-hydroxysilanes 5 with a base such as sodium hydride or potassium hydride leads to preferential -elimination to give alkene 3a as major 

Whether the formation of alkene 3 proceeds directly from alkoxide 4 or via a penta-coordinated silicon-species 6, is not rigorously known. In certain cases—e.g. for /3-hydroxydisilanes (R = SiMes) that were investigated by Hrudlik et al —the experimental findings suggest that formation of the carbon-carbon bond is synchronous to formation of the silicon-oxygen bond  

The Peterson olefination concerns the construction of double bonds from trialkylsilyl-substituted organometallics and carbonyls. The reaction involves the formation of an /ar-hydroxysilane, which then undergoes elimination to give the alkene. Elimination can take place under either acidic or basic conditions. 

Peterson went on to describe reactions of several lithiated silanes with carbonyls compounds, all giving the desired alkenes in good yields, albeit with very little stereoselectivity. In 1975 however, Peterson and Hudrlik published their studies on the stereoselective elimination of the hydroxyalkylsilyls. The reduction of 5-trimethylsilyl-4-octanone 10 was carried out with DIBAL-H to give one diastereoisomer, 11. The authors found that elimination with sodium or potassium hydride gave /ra 5-4-octene as the major isomer 12, while elimination under acidic conditions resulted in predominantly c/5-4-octene 13. Mild conditions were employed, affording stereochemical purity of up to 95% with excellent yields. 

Due to the mechanism of action, the Peterson olefination is a very versatile method of forming carbon-carbon double bonds. In particular, the reaction can be carried out under basic or acidic conditions giving rise to either the trans or cis isomer respectively. In cases where the stereoselectivity of the new double bond is irrelevant, the ability to employ either acid or basic conditions means that potentially sensitive functionalities in the remainder of the molecule can be suitably accommodated. 

The mechanism begins with the addition of a silyl-substituted carbanion 14 to a carbonyl compound 15 an aqueous work-up then leads to a diastereomeric mixture of yff-hydroxyalkylsilanes, often isolable and sometimes separable. The stereo-selectivity of the reaction can be controlled by the steric demands of the silyl group the use of more sterically demanding silyl groups results in the erythro isomer as the major product. 

A subsequent basic elimination can proceed via two pathways (i) deprotonation of the hydroxyl followed by a silyl 1,3-shift 20, (ii) deprotonation followed by formation of a penta-coordinate 1,2-oxasiletanide 21 which then collapses to give the alkene product, 23. 

The acid-catalyzed Peterson olefination is presumably an E2-elimination, that is, a one-step reaction. On the other hand, the base-induced Peterson olefination probably takes place via an intermediate. In all probability, this intermediate is a four-membered heterocycle with a pentavalent, negatively charged Si atom. This heterocycle probably decomposes by a [2+2]-cycloreversion just like the oxaphosphetane intermediate of the Wittig reaction (Section 4.7.3). 

3 Oxaphosphetane Fragmentation, Last Step of Wittig and Horner-Wadsworth-Emmons Reactions 

In addition to the Wittig- und Homer-Wadsworth-Emmons reactions, we know a third alkene-forming reaction between carbonyl and phosphororganic compounds, i.e. the Wittig-Homer reaction. In Section 11.2, you will learn that in the course of this reaction a. syn-elim-ination of Ph2P(=0)0 takes places, i.e. another / elimination of I let1/I let2. 

Alkene Synthesis, in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 1, 729, Peigamon Press, Oxford, 1991. 

Alkenes from a-silyl carbanion and carbonyl compounds. Also known as sila-Wittig reaction. 

Kawashima, T. The Peterson and Related Reactions in Modem Carbonyl Olefination Takeda, T. (ed.), Wiley-VCH Weinheim, Germany, 2004, 18—103. (Review). 

3) aldol reaction of enolates derived from a-silyl ketones with aldehydes and 

R =alkyl, aryl R = alkyl, aryl, CO2R, CN, CONR2, CH=NR, SR, SOR, SO2R, SeR, SiRs, OR, BO2R2 R, R-alkyl, aryl, H 

The exact pathway of the Peterson reaction is still not clear despite the intensive research effort. Most of the mechanistic studies suggest that both the stepwise and concerted pathways are feasible under basic conditions. In the concerted pathway a pentacoordinate 1,2-oxasiletanide is formed. The stepwise pathway is expected when chelation control operates in the reaction. The driving force is the formation of a very strong Si-0 bond. Under acidic conditions the 3-hydroxysilane undergoes an E2 elimination to afford the other alkene isomer. 

Tius et al. reported a formal total synthesis of the macrocyclic core of roseophilin. The aliphatic five-membered ring of this core was prepared via a variant of the Nazarov cyclization. The precursor for this cyclopentannelation reaction is an ( )-a, 3-unsaturated aldehyde, which was prepared using the Peterson ole nation on the f-butylimine of 5-hexenal. First the a-TMS derivative of the imine was generated then after a second deprotonation, the additon of isobutyraldehyde gave the ( )-a, 3-unsaturated imine upon aqueous work-up. Acidic hydrolysis of this imine gave the desired ( )-a,(3-unsaturated aldehyde in good yield. 

In the final stages of the total synthesis of (+)-brasilenyne by S.E. Denmark and co-workers, the introduction of the (Z)-enyne side chain was accomplished with the Peterson olefination. The aldehyde was treated with lithiated 1,3-b/s(triisopropylsilyl)propyne at low temperature followed by slow warming of the reaction mixture to ambient temperature to give a 6 1 (Z ) ratio of the desired enyne. 

Peterson olefmation. In Name Reactions for Homologations-Part I Li, J. J., Corey, E. J., Eds., Wiley Sons Hoboken, NJ, 2009, pp 521-538. (Review). 

Galano, J.-M. Audran, G. Monti, H. Tetrahedron Lett. 2001, 426X25. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 199, Springer-Verlag Berlin Heidelberg 2009 

---

Peterson Olefination review . Synthesis 1984, 384 Organic Reactions 1990, 38 1. 

Lastly, a-trimetfayisflyl enolates have been added to trifluoromethyl ketones to effect Peterson olefination of the tnfluoromethyl ketones [IS (equation 13)... 

The above mechanism involves a-opening of the epoxysilane, followed by a 1,2-elimination of a /3-hydroxysilanc (Peterson olefination, Chapter 10). However, it has recently been shown that aj8-dihydroxysilanes, particularly t-butyldimethylsilyl species, undergo an acid-catalysed sila-pinacol rearrangement to produce /J-aldehydo- and /i-kctosilancs (5) ... 

The main utility of Peterson olefination lies in the contrasting stereochemical requirements (6) for elimination, use of base requiring a syn conformation whereas acid conditions demand an anti conformation, with complementary geometrical results ... 

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. 

The anti elimination can also be achieved by converting the (3-silyl alcohols to trifluo-roacetate esters.273 The stereoselectivity of the Peterson olefination depends on the generation of pure syn or anti P-silylalcohols, so several strategies have been developed for their stereoselective preparation.274... 

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... 

As is the case with the Wittig and Peterson olefinations, there is more than one point at which the stereoselectivity of the reaction can be determined, depending on the details of the mechanism. Adduct formation can be product determining or reversible. Furthermore, in the reductive mechanism, there is the potential for stereorandomization if radical intermediates are involved. As a result, there is a degree of variability in the stereoselectivity. Fortunately, the modified version using tetrazolyl sulfones usually gives a predominance of the E-isomer. 

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. 

A number of copolymers 14 have been prepared by cothermolysis of the new derivatives, 12 and 13, with the simplest phosphoranimine precursors, MegSiN = P(OCH2CFg)(Me)R (11). The copolymers 14 derived from the Peterson olefination products 13 are soluble, non-crosslinked materials with molecular weights in the 30,000 -100,000 range. This implies... 

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. 

A bis-vinylogue of a cyclopropylcarbinol 57 arises by standard transformations (Eq. 59) from the Peterson olefination product 56. Here too, acid induced rearrangement proceeds exclusively to the cyclobutanone and not to larger ring products93). 

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. 

---