Substituted Activated Olefins

Subsequently, the MBH reaction of (3-substituted crotonaldehyde with imines or nitroolefins catalyzed by the combination of imidazole or DABCO with proline was independently reported by Barbas and Cordova et al to furnish highly enantiomerically enriched MBH-type products with jS-substituted enal moieties with excellent ( )-selectivity (Chapter 2.6.1). 

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Vinylalumination of Fluoro-aldehydes and Ketones. Okie of the problems of MBH reaction is the lack of reativity of p-substituted activated olefins. We applied the vinylalumination reaction reported by Tsuda and co-workers (13) for the synthesis of fluorinated MBH products (Scheme 14) (77). Due to the high reactivity of fluorinated... 

Aryl and vinylic bromides and iodides react with the least substituted and most electrophilic carbon atoms of activated olefins, e.g., styrenes, allylic alcohols, a,p-unsaturated esters and nitriles. 

Several other complexes, M(CNBu )jL (L = an activated olefin), have also been reported recently (110). This group of complexes, with the ligands (L) including maleic anhydride, fumaronitrile, and tetracyano-ethylene, arises from isocyanide ligand substitution by the olefin. Less active olefins such as ethylene and diphenylacetylene, and azobenzene did not react. 

Some interesting differences are found between the reactions of Co(I) and Co—H complexes. For example, [Co (DMG)2py] will react at pH 10-11 with activated olefins to give the -substituted complexes [XCH2CH2Co(DMG)2py)], where X is COOH, COOR, CN, etc. but at pH 7-8, where the complex is present as the hydride, the a-substituted derivatives [CHjCHXCo(DMG)2py] are formed 163, 149). Schrauzer, Weber, and Beckham were able to show that the reactions at higher pH proceeded via the intermediate formation of the 7r-olefin-Co(I) complex 159). The reactions involving Co(I) appear generally to be reversible and the addition of Co—H irreversible (see also Section V,C and VI,B). We can, therefore, write the scheme... 

Maier, L., The addition of hypophosphite esters to activated olefins, a new method for preparing substituted ethyl phosphinates, Helv. Chim. Acta, 56, 489, 1973. 

Catalytic asymmetric hydrosilylation of prochiral olefins has become an interesting area in synthetic organic chemistry since the first successful conversion of alkyl-substituted terminal olefins to optically active secondary alcohols (>94% ee) by palladium-catalyzed asymmetric hydrosilylation in the presence of chiral monodentate phosphine ligand (MOP, 20). The introduced silyl group can be converted to alcohol via oxidative cleavage of the carbon-silicon bond (Scheme 8-8).27... 

P-Cyclodextrin was modified by attaching 2-(diphenylphosphinoethyl)-thio- (127) and 2-bis(diphenylphosphinoethyl)amino- (126) moieties at the C-6 position [8-11]. The resulting macroligands were reacted with [ RhCl(NBD) 2] to provide the corresponding cationic rhodium-bisphosphine complexes. These catalysts showed pronounced selectivity due to complexation of the substrate by the CD unit adjacent to the catalyticaUy active metal center. For example, in competitive hydrogenation of similarly substituted terminal olefins (Scheme 10.4), 4-phenyl-but-l-ene was... 

Another type of Cinchona alkaloid catalyzed reactions that employs azodicarbo-xylates includes enantioselective allylic amination. Jprgensen [51-53] investigated the enantioselective electrophilic addition to aUyhc C-H bonds activated by a chiral Brpnsted base. Using Cinchona alkaloids, the first enantioselective, metal-free aUyhc amination was reported using alkylidene cyanoacetates with dialkyl azodi-carboxylates (Scheme 12). The product was further functionalized and used in subsequent tandem reactions to generate useful chiral building blocks (52, 53). Subsequent work was applied to other types of allylic nitriles in the addition to a,P-unsaturated aldehydes and P-substituted nitro-olefins (Scheme 13). 

Simply substituted thiocarbonyl ylides, including the parent system, react with activated olefins to form tetrahydrothiophene derivatives (30,31,52,53,131). Recently, the thermal desilylation method was applied toward the preparation of the Ceo-fullerene-fused tetrahydrothiophene 71 (132) (Scheme 5.26). 

The method is quite useful for particulary active alkyl halides such as allylic, benzylic, and propargylic halides, and for a-halo ethers and esters, but is not very serviceable for ordinary primary and secondary halides. Tertiary halides do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and elimination predominates. The reaction can also be applied to activated aryl halides (such as 2,4-dinitrochlo-robenzene see Chapter 13), to epoxides,217 and to activated olefins such as acrylonitrile, e.g.,... 

TPPMS serves as ligand in a variety of catalysts for hydrogenation,6 hydroformylation, and C-C bond formation.7 In aqueous solutions, it reacts with activated olefins,8 alkynes,9 and aliphatic as well as aromatic aldehydes,10 giving the corresponding substituted alkylphosphonium salts. 

The investigation on the hydroformylation of optically active olefins, started with 3-methyl-substituted a-olefins, has been extended to olefins... 

Michael addition of substituted electrophilic olefins to the activated 2-substituent yields pyrrolooxazines on cyclization.244-248... 

The usual substitution pathway for activated olefins is illustrated by Scheme 34 regarding anionic nucleophiles. In 73, R1 and R2 are electron-attracting groups L is the leaving group (usually a halogen atom) and Y is the charged nucleophile (in particular, alkoxides and thioalkoxides). 

The third type of cycloaddition results from the reaction of cyclopropanones with activated olefins. For example, dimethylketene adds to methyl substituted cyclopropanones affording the spiro lactones 153 a—c. 96,n8,i22b) Similarly the ortho ester 154 is formed from 1,1-dimethoxy-ethylene and 2,2-dimethylcyclopropanone 154 dimerizes to 155 upon standing. ng>... 

In addition to the cathodic hydrodimerization of activated olefins [see 3.2.1.1], the electrosyntheses of substituted benzaldehydes are among the few electroorganic reactions which are carried out on a large scale industrially. 

Various mechanistic routes, such as addition, cyclization, etc., are available for the carbanions formed in the reactions of nucleophiles with activated olefins (Patai and Rappoport, 1962). Their competition with substitution can give information regarding the life-time of the carbani-onic intermediate. The retention of configuration of both isomers of... 

Anodic dimerization of electron-rich olefins, the mirror image process to cathodic hydrodimerization of activated olefins (Sect. 12.2), affords a one-step synthesis for substituted butanes(Eq. (175) ) 268)( dienes (Eq. (176) ) 26S precursors of polyenes (Eq. (177)) 36,385 and 1,4-dicarbonyl compounds (Eq. (178)) 35>36). 

Organometallics are formed at the cathode if transient radicals produced in reductions react with the active electrode. This occurs as a side reaction in cathodic coupling (Sect. 12.2, Eq. (185)) of carbonyl compounds, e.g., of acetone 3 9 or of activated olefins, e.g., of methyl vinyl ketone 41or acrylonitrile. Furthermore, in cathodic cleavage (Sect. 13.2, Eq. (227) ) of alkyl bromides or iodides organometallics are formed, e.g., ME(CH2CH2CN)2(ME = Pb, Tl, Sn, Hg) 481 bis(p-substituted benzyl)mercury 485 or dicyclopropylmercury 489 ... 

The extent of stereoselectivity in the chiral synthesis can be checked by determining the enantiomeric excess of the optically active olefins in the products. The optical purity was determined by gas chromatographic resolution of enantiomers by means of an optically active column. Thermostable substituted cyclodextrins are well suited as asymmetric phases (206). The trimer, 2,4-dimethyl-l-heptene, was resolved into its enantiomers by capillary gas chromatography with an octakis(6-0-methyl-2,3-r/-0-pentyl-)-7-cyclodextrine phase. 

Eq. 52 and 53 demonstrate remarkable characteristics of this [3 + 2]-cycloaddition starting with a pure diastereomer 130, two stereoisomeric cyclopentanes 131 are obtained. This stereorandom outcome is most simply rationalized assuming a stepwise mechanism with a 1,5-zwitterion as an intermediate in the cycloaddition. The vinylcyclopropane 132 only gives five-membered ring products 133 and no cyclo-heptene derivative, which would result from a conceivable [5 + 2]-cycloaddition. Less activated olefins or cyclopropanes do not undergo a similar [3 + 2]-cycloaddition. Due to the specific substitution pattern, the cyclopentane formation from these siloxycyclopropanes is of no preparative value. 

Ruthenium(O) complexes such as Ru(COD)(COT) catalyze the dehydrohalo-genative coupling of vinyl halides with olefins to give substituted conjugated dienes in a Heck-type reaction [11]. Thus, alkenyl halides readily react with activated olefins to produce dienes 16 (Eq. 7). Oxidative addition of vinyl halide, followed by regioselective insertion of an electron-deficient olefin and by -hydrogen elimination leads to the diene. 

Keywords Organozinc, Organolithium, Grignard reagent, Copper, Conjugate addition, Nucleophilic addition, Alkylation, Activated olefin, Enone, Nitroalkene, p-Substituted carbonyl... 

On the basis of this palladium-mediated Michael addition cyclization process, a novel two-step synthetic entry into functionalized furan derivatives 67 has also been devised (Scheme 28). Substitution of benzylidene (or alkyli-dene) malonates for their ethoxymethylene analog (65) as activating olefins gave rise to the formation of the corresponding 2-ethoxy-4-arylidene tetrahy-drofurans 66. An in situ addition of potassium ferf-buloxidc induced a decar-boxylative elimination reaction which was followed by an isomerization of the exocyclic double bond. The entire process successively involved a conjugate addition, a palladium-catalyzed cyclization-coupling reaction, a base-induced eliminative decarboxylation, and finally, a double bond isomerization [73]. 

The reactions in this section cover the conjugate (Michael) addition of various lithiated nucleophiles to activated olefins such as enones and enoates. Lithium enolates are formed as intermediates during the addition process. They can be treated as such and trapped, for instance, by an electrophile to provide ketones or esters substituted both in the a and positions. We will focus only on the most important information relevant to the intermediate enolates, and those are rarely discussed in the literature on the Michael addition. The reader can advantageously consult Chapter 14 of the first part of this volume133, which is entirely dedicated to the organolithium additions to double bonds, for a more extensive coverage of the topic. 

Asymmetric olefination. The anion (KDA) of the enantiomers of 1 react with substituted cyclohexanones with the opposite sense of induction to give optically active olefins. 

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