Peterson olefin-formation

Isomerization of silicon from carbon to alkoxide is rare since olefin formation via 1,2-elimination of /3-silyloxy is rapid (known as the Peterson olefination, equation 23) °. 

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 ... 

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. 

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. 

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. 

Synthesis of these prolylamide mimics is based on the Peterson olefination between tert-butyl a-fluoro-a-trimethylsilyl acetate and a protected hydroxypentanone. Further introduction of the amino group is rather difficult. This step has been accomplished through conversion of the ester into aldehyde, followed by the formation of the silylated aldimine with LiHMDS, and then the addition of methyl lithium (Figure 7.23). ... 

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). 

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. 

Reaction of DMSB with triphenylsilyl-substituted oxiranyllithium leads to the formation of an olefinic silanol via sequential (1) coordination to the silicon, (2) Si-C bond migration, and (3) Peterson-type Si-O elimination to furnish the alkene. A pentacoordinate siliconate intermediate is presumably involved in this transformation. Therefore, it was reasonable to expect that addition of a nucleophile (methyllithium or lithium t>-propoxide) to an oxiranyl-substi-tuted SCB, which could generate a similar intermediate, would induce the C-Si bond migration to form the same silacyclopentane. Indeed, this alternative order of addition sequence provides the corresponding silanol with better efficiency (84% yield vs. 44%, Scheme 36). 

In reaction (28) y-elimination of LiCl with the formation of an epoxide is obviously faster than P-elimination of Me3SiOLi (Peterson-olefination). Seyferth and his collaborators34) found that this reaction takes place when bis(trimethylsilyl)bromo-methyllithium is reacted with carbonyl compounds, albeit not stereoselectively (Eq. (30)). In contrast, thermal dehydrohalogenation of 1,1-dichloro-l-phenyl-dimethylsilyl-alkanes furnishes Z-olefins only (Eq. (31)) according to the results of Larson et al. 35) ... 

The acid or base elimination of a diastereoisomerically pure p-hydroxysilane, 1, (the Peterson olefination reaction4) provides one of the very best methods for the stereoselective formation of alkenes. Either the E- or Z-isomer may be prepared with excellent geometric selectivity from a single precursor (Scheme 1). The widespread use of the Peterson olefination reaction in synthesis has been limited, however, by the fact that there are few experimentally simple methods available for the formation of diastereoisomerically pure p-hydroxysilanes.56 One reliable route is the Cram controlled addition of nucleophiles to a-silyl ketones,6 but such an approach is complicated by difficulties in the preparation of (a-silylalkyl)lithium species or the corresponding Grignard reagents. These difficulties have been resolved by the development of a simple method for the preparation and reductive acylation of (a-chloroalkyl)silanes.7... 

Reaction Mechanism The mechanism of the sodium hydroxide-catalyzed elimination of hexamethyldisiloxane may easily be understood when the reaction is compared to the well-known Peterson olefination in organic chemistry [24], Provided that an enolate anion is formed as an intermediate, either directly or via a proceeding hydrolysis of the 0-Si bond with traces of water which are always present on the hot surface of the crude catalyst, trimethylsilanolate splits off readily and thus the PsC triple bond is introduced into the molecule (Eq. 5). Subsequent attack of trimethylsilanolate at the trimethylsiloxy group of the starting compound results in a formation of hexamethyldisiloxane and the initial enolate anion so that the reaction circle is closed. 

The synthesis of alkylidene and allylidene cyclopropanes reported in this section takes advantage of the availability 77 78,81 a-82) of l-(l-silyl) cyclopropyl carbinols from a-lithio cyclopropylsilanes and carbonyl compounds. It, however, suffers from the sometimes modest yields obtained when ketones are involved (Schemes 21 a, 47) in the Peterson olefination reaction 77,78,81a) (Schemes 21, 48). This reaction seems much more difficult to achieve than when straight-chain analogs are involved and resembles the cases of allenes 1211 and chlorocyclopropenes120) reported by Chan. For example, thionyl chloride alone is not suitable for that purpose 77,136) but further addition of tetra-n-butylammonium fluoride (20 °C, 15 hrs) leads to the formation of undecylidene cyclopropane77,136 in 46% yield from the corresponding l-(l-silyl)cyclopropyl... 

Bis(phenylsulfanyl)](trimethylsilyl)methyllithium and trimethylsilyloxirane do not afford a homo-Peterson reaction product, but a cyclopropane 4 a with a shifted phenylsulfanyl group. [Bis(phenylsulfanyl)](trimethylsilyl)methyllithium may be looked on as a carbenoid species which is in equilibrium with carbene and phenylsulfonate. This equilibrium may lie towards the carbanion. On addition of trimethylsilyloxirane, phenylsulfonate is trapped with formation of an alkoxide, which corresponds to the intermediate of a Peterson olefination of formaldehyde, and leads to phenyl vinyl sulfide. This provides a reaction partner for the liberated carbene giving cw-l,2-bis(phenylsulfanyl)-l-trimethylsilylcyclopropane (4a) in a stereospecific [2-1-1]... 

The Peterson olefination is a two-step process for the formation of alkenes from an a-silylcarbanion and an aldehyde or ketone. The first step is an addition reaction that affords both syn and anti p-hydroxysilanes. The stereochemistry is then controlled during the elimination step by using either an acid or a base. Reviews Kano, N. Kawashima, T. In Modem Carbonyl Olefination-Methods and Applications Takeda, T. Ed. Wiley-VCH Weinheim, 2004 Chapter 2 The Peterson and Related Reactions, pp. 18-103. (b) Kelly, S. E. In Comprehensive Organic Synthesis Trost, B. M. Fleming, 1., Eds. Pergamon Oxford, 1991 Vol. 1, Chapter 3.1 Alkene Synthesis, pp. 731-737. (c) Ager, D. J. Org. React. 1990, 38, 1-223. (d) Ager, D. J. Synthesis 1984, 384-398. 

The stereochemistry of the Peterson reaction has been investigated. When unsymmet-rically substituted a-silylcarbanions react with aldehydes or unsymmetric ketones, E or Z olefins are produced. In many cases the E Z ratio is 1 1, however, some workers have reported a predominance of cis olefins when aldehydes are employed. Typical results are given in Table 15. Unlike the Wittig reaction the stereochemical outcome of the Peterson reaction is insensitive to counterion, solvent, added salts and temperature255. Stereochemical control of the Wittig reaction usually depends upon the reversibility of the first step. However, as discussed earlier, the first step of the Peterson reaction is irreversible. Thus the stereochemical outcome is determined solely by the relative rates of formation of threo and erythro 0-silyl alkoxides (/ct and k in Scheme 5). 

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