Olefination methods

The reactions described in this chapter include some of the most useful synthetic methods for carbon-carbon bond formation the aldol and Claisen condensations, the Robinson annulation, and the Wittig reaction and related olefination methods. All of these reactions begin by the addition of a carbon nucleophile to a carbonyl group. The product which is isolated depends on the nature of the substituent (X) on the carbon nucleophile, the substituents (A and B) on the carbonyl group, and the ways in which A, B, and X interact to control the reaction pathways available to the addition intermediate. 

There is no real need today for new carbonyl olefination methods as such. But though some techniques have been developed for highly stereoselective carbonyl olefination further progress in this direction would be welcome. 

Scheme 14.6 The Julia-Lythgoe-Kocienski olefination method.

At this point it should be noted, that olefination involving reaction of PO-stabilized carbanions like those from phosphonates, phosphinates, phosphine oxides, phos-phonamides or thiophosphonates (Horner reaction 47), Horner-Wadsworth-Emmons reaction48 ) with carbonyl compounds almost exclusively yields ( )-olefins. This olefination is essentially restricted to PO-activated compounds carrying stabilizing groups on the carbanionic C-atom. However, these compounds are more reactive than the corresponding resonance-stabilized ylides. Therefore, this olefination method... 

Reductive elimination of /i-hydroxysulfoximines provided the basis for a related olefination method put forward by C.R. Johnson and coworkers [91 ] (Scheme 64). 

The bromination of a-chloro ethers proceeds readily and represents the second stage in the Boord synthesis of olefins (method 21) ... 

A conjugated double bond system undergoes 1,4-addition (Thiele s rule) for example, butadiene and an equimolar quantity of bromine yield 1,4-dibromo-2-butene (90%). On the other hand, chlorination of butadiene in the liquid or vapor phase furnishes about equal amounts of 1,2-and 1,4-addition products. Other polyfunctional compounds resulting from this method of preparation include dihalogenated acids, esters, aldehydes, and ketones. < The addition of bromine to unsaturated ethers yields dibromo ethers which are used as intermediates in the synthesis of olefins (method 21) and olefinic alcohols (method 99) ... 

The Peterson olefination is a connective alkene synthesis and represents a useful alternative to the Wittig reaction. The precursors for the Peterson olefination are 3-hydroxy-alkyltrimethylsilanes which undergo P-elimination of trimethylsilanol under basic or acidic conditions to furnish stereodefined alkenes. This olefination method is especially valuable for the preparation of terminal and exo-cyc ic double bonds and for the methylenation of hindered ketones where the Wittig reaction is problematic. Also, the... 

A (Z)-selective Peterson olefination was the key step in the first enantioselective total synthesis of both enantiomers of lancifolol in the laboratory of H. Monti.This synthetic approach allowed the correlation of the relationship between absolute configuration and specific rotation. It is important to mention that no other olefination method could be applied successfully in installing this (Z)-alkene moiety. 

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. 

Review Matsubara, S. Oshima, K. In Modern Carbonyl Olefination-Methods and Applications. Takeda, T., Ed. Wiley-VCH Weinheim, 2004 Chapter 5 Olefination of Carbonyl Compounds by Zinc and Chromium Reagents, pp. 214-220. 

Haas, A., Lieb, M., and Zwingenberger, J., Synthesis of hi5(trifluoromethyl)substituted olefins. Methods of preparation and properties, Liebigs Ann. Org. Bioorg. Chem., 2027, 1995. 

Takeda, T. Modern Carbonyl Olefination Methods and Applications Wiley-VCH Weinheim, 2004. 

Application of this catalyst system to propargyl alcohols provides a, 3-unsaturated aldehydes (Equation 1.17) and ketones (Equation 1.18) [18]. The ease of accessibility of the substrates by simple addition of terminal alkynes to aldehydes followed by this redox isomerization constitutes a highly chemoselective and atom economic strategy to these unsaturated carbonyl compounds. The chemoselectivity problems of the direct aldol condensation and the poor atom economy of olefination methods make this new strategy the most efficient and reliable approach to these units. 

Warren has used a variation of his phosphine oxide-based olefination method to synthesise single isomers (E or Z) of unsaturated carboxylic acids.23 a-Diphenylphosphinoyl ketones (32) are reduced by sodium borohydride to give diastereomeric mixtures of the corresponding alcohols (33) and (34). These alcohols can be converted to the lactones (35) and (36) which can be separated and individually converted stereospecifically into (Z)-(37) and (E)-(38) alkenes by base treatment (Scheme 6). In many cases it is possible to reduce p-ketophosphine oxides (39) and enones (41) stereoselectively to the ery/Aro-alcohols (40) and (42), respectively, using sodium borohydride in the presence of cerium chloride (Scheme 7).24 An earlier report that reduction in the presence of cerium salts did not cause reversal of stereochemistry compared to reduction with borohydride alone appears to be true only of the compounds studied in that report. The carbanions of 3-hydroxypropylphosphine oxides (43) have been reported to undergo O- to C-acyl transfer to give the p-ketoalkylphosphine oxides... 

Pyrolysis of the oxide of tertiary amine 1 yields olefin 2 and hydroxylamine 3. This olefination method is known as the Cope elimination reaction.1-3... 

As an alternative to an olefination method, the Cope elimination can be used as a preparative method for unsymmetrical hydroxylamines. Addition of unsymmetrical secondary amine 41 to a,p-unsaturated compounds gave access to compound 42, which underwent oxidation and Cope elimination to yield the unsymmetrical hydroxylamine product 44.16... 

The stereospecific olefination method involving synthesis, separation, and base-catalysed, decomposition of diastereomeric P-hydroxyalkylphosphine oxides has been used for the preparation of pure isomers of y,S-unsaturated acetals (Scheme 11). The same principle has been extended to trisubstituted alkenes. The yields are generally still good, but the diastereomeric hydroxyphosphine oxides involved are less stable in some cases and the routes to them are less stereoselective. However, the method works reasonably well for the synthesis of ( )-and (Z)-allylic amines (Scheme 12). Unfortunately, (2-substituted-2-amino)-... 

Predict the products of each precursor by the hydration of olefins method. 

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