Peterson alkenation

Mechanism The Peterson alkenation offers the synthesis of desired alkene stereoisomer by careful separation of the two diastereomeric intermediate P-hydroxysilanes and subsequently performing elimination under two different conditions. 

The order of reactivity of alkoxides - K > Na Mg - is consistent with the higher electron density on oxygen, hence increasing the alkoxide nucleophilicity. When the a-silylcarbanion contains electron-withdrawing substituents, the Peterson alkenation directly forms the alkene, without the isolation of (3-hydroxysilane. 

Synthesis and Reaction Chemistry of a,p-Unsaturated Acyl Complexes Derived from (2). Two methods for the preparation of optically active ( )- and (Z)-a,p-unsaturated iron acyls from (2) have been reported." One method involves aldol condensation of (2) with aldehydes followed by 0-methylation to produce diastereomeric acyls (18). This mixture (18) is then treated with Sodium Hydride to produce predominantly ( )-a,p-unsaturated acyl complexes (19) (eq 13). Alternatively, (2) can be depro-tonated and treated with Chlorotrimethylsilane to produce the C-silylated complex which is subsequently deprotonated and treated with an aldehyde. This Peterson alkenation produced mixtures... 

C2 symmetric, chiral ketene dithioacetals containing the binaphthyl moiety can be prepared by Peterson alkenation of the title reagent (eq 6). The corresponding bis-sulfone affords one exo and one endo adduct with cyclopentadiene (eq 7) which, once separated and desulfonylated, give the corresponding norbomenes (see 1,1 -Bis(phenylsulfonyl)ethylene) ... 

A series of molybdenum alkylidene complexes react with aldehydes, and in some cases ketones, to give the product of methylenation (equation 33). Some of the examples appear to involve an alkylidene, while others may follow an addition-elimination route typical of the Peterson alkenations. Probably the most interesting aspect of this work is the observation that some of the methylenation reactions can be carried out in aqueous or ethanolic media (equation 33). ... 

Metallated allylsilanes have also been examined in terms of the effects of various gegenions on a-versus y-additions to aldehydes. Using allylaminosilane (49), Tamao and Ito have shown that transmetal-lation of the lithiated intermediate to copper using CuCN (1 equiv.) leads to a >95% preference for y-ad-duct (51 Scheme Other metals such as magnesium, zinc and titanium show a strong preference for a-attack (>95%), which ultimately leads to dienes (50) following Peterson alkenation. 

Anions of a-silyl phosphonates of type (153) also undergo additions to carbonyl compounds. The corresponding addition products, 3-silyl alkoxides, can react with ketones to yield the product of the Peterson alkenation or the Wittig reaction. In practice only the Peterson product (154) is obtained, indicating that loss of OSiMes is faster than elimination of C PPhs (Scheme 68). 72 If the a-silyl carbanion is adjacent to a chlorine atom (155), an internal displacement reaction follows the initial formation of the -silyl alkoxide, and epoxides (156) are formed (Scheme 69). 74... 

The methylenation of ketones and aldehydes by the Wittig reaction is a well-established and selective methodology. Unlike addition-elimination methods of alkene formation, the Wittig proceeds in a defined sense, producing an alkene at the original site of the carbonyl. The Wittig reaction is not considered here, but is used as the standard by which the methods discussed are measured. The topics covered in the methylenation sections include the Peterson alkenation, the Johnson sulfoximine approach, the Tebbe reaction and the Oshima-Takai titanium-dihalomethane method. 

In the case of base-induced elimination, the Peterson alkenation relies on the strong bond formed between silicon and oxygen, and the ready propensity for silicon to be attacked by alkoxide, to drive the reaction. In the original study by Peterson, the -silylcarbinols were prepared by the addition of (trimethylsilyl)methylmagnesium chloride to the carbonyl. The caibinols were subsequently eliminated by treatment with sodium or potassium hydride or with sulfuric acid to form the methylene derivatives in excellent yield. The Peterson reaction has proven to be of general utility in the synthesis of alkenes. ... 

Unlike the Peterson alkenation, which is in principle similar, the phosphine oxide anion addition can be controlled to produce predominantly the erthyro isomer (206). The threo isomer can be obtained by selective reduction of the a-ketophosphine oxide (210), allowing highly stereoselective alkene fonna-tion. Since a two-step sequence is employed, this reaction does not require a stabilizing functionality to be conjugated to the phosphine oxide in order to produce the alkene. In fact, unlike the phosphonate HWE reagents, the reaction of a ketophosphine oxide (211) with a carbonyl derivative does not occur to produce the unsaturated carbonyl (213 Scheme 30). ° The addition step is presumably too rapidly reversible and the elimination of phosphine oxide too slow. 

In analogy to the Peterson alkenation, the intermediate hydroxyphosphine oxidn (269) cm be prepared by addition to epoxide derivatives (268 Scheme 36). Overall yields are high for this process, and this sequence can be applied to the synthesis of phosphonate intermediates as well. Warren has studied hydroxy-directed epoxidation. Provided the allylic phosphine oxide is trisubstituted, as is (270) in equation (6S), these oxidations proceed with good selectivity. Ring opening can then be undertaken to generate the hyth-oxyphosphine oxide. 

In Section 3.1.3.1, the advantages of the Peterson alkenation in comparison to die Wittig reaction were detailed. The by-product (hexamethyldisiloxane) is volatile and is easier to remove than the phosphine... 

The term Peterson alkenation has been used to describe the elimination of a functionalized organo-silicon compound with alkene formation for substrates synthesized by these methods. In accordance with the mechanistic definition outlined in the introduction to this cluq)ter, such topics are not considered in detail in this review. For the purpose of this discussion, the Peterson alkenation will be considered as the addition of an anion derivative to a carbonyl compound, followed by elimination to the alkene. 

As mentioned in the previous section, the Peterson reaction proceeds by an irreversible addition of the silyl-substituted carbanion to a carbonyl. It has generally been assumed that an intermediate p-oxidosi-lane is formed and then eliminated. In support of this mechanistic hypothesis, if an anion-stabilizing group is not present in the silyl anion, the p-hydroxysilanes can be isolated fixrm the reaction, and elimination to the alkene carried out in a separate step. Recent studies by Hudrlik indicate that, in analogy to the Wittig reaction, an oxasiletane (304) may be formed directly by simultaneous C—C and Si—O bond formation (Scheme 43). The p-hyd xysilanes were synthesized by addition to the silyl epoxide. When the base-induced elimination was carried out, dramatically different ratios of cis- to rranr-alkenes were obtained than from the direct Peterson alkenation. While conclusions of the mechanism in general await further study, the Peterson alkenation may prove to be more closely allied with the Wittig reaction than with -elimination reactions. 

The use of sulfur in the Peterson reaction can be extended to the optically pure lithio anion of S phe-nyl-S-(trimethylsilyl)tnethylW-tosylsulfoxiniine (330 equation 76). Unlike most Peterson alkenations t reaction is selective for the formation of the ( )-alkene isomer (331) with aldehydes. In addition, the stereochemistry of the sulfoximine is maintained. 

Comparative examples of the Wittig reaction and the Peterson alkenation with ketones (353 equation 82) and (355 equation 83), epoxy ketones (351 equation 81), or protected a-hydroxy ketones (348 equation 80) have tqtpeared. The reactions can proceed with high kinetic control for the (Z)-isomer and, as a result, the Peterson technology may form complementary isomers to the Wittig reaction. ... 

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