Stereochemistry activated alkenes

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

An interesting intramolecular variation of this reaction provides oxazolidones, which may be hydrolyzed to synthetically useful optically active 2-amino-3-butenols (eq 8). The absolute stereochemistry of the stereocenter formed is dependent upon the geometry about the double bond of the 2-butenylene dicarbamate substrate. A related Pd -promoted [3 + 2] cycloaddition of an activated alkene with a 2-(sulfonylmethyl)-2-propenyl carbonate, using the bis(hydroxyalkyl)-substituted ligand (8), gave methylenecyclopentane derivatives with high asymmetric induction. ... 

This section concerns the classical hydrodimerization of alkenes activated by electron-withdrawing substituents, as in Eq. (1). The literature in this area is extensive and this chapter cannot be exhaustive. The focus will be on typical reactions and general conclusions, which may serve as guidelines for further work. Special emphasis will be put on the effect of reaction conditions on the mechanisms, product selectivity, and stereochemistry. Section II.A deals with the monoactivated alkenes, that is, structures of the type 1 where R and R" are H, alkyl, or aryl Sec. II.B deals with intramolecular coupling reactions where two identically activated alkenes are linked together within the same molecule. The reactions of alkenes activated by two electron-withdrawing groups either in a, a- or in a,yS-positions, are treated in Sec. II.C. 

In all cases, Grubbs found that the cis-to-trans ratio was always 1 1, thus demonstrating that a-activation does not influence the rate or stereochemistry of alkene insertion. The result of the experiment was the key piece of evidence supporting the Cossee mechanism for Z-N polymerization long sought after by chemists. The experiment allowed researchers to make a clear distinction between metathesis and Z-N polymerization, the former involving the chemistry of the M=C bond and the latter that of the M-C bond.87... 

Metal-activated alkene additions can be classified as stoichiometric or catalytic processes. Stoichiometric processes for THP synthesis typically involve the use of mercury(II) salts and to a lesser extent iodo and seleno reagents. The progress of intramolecular oxymercuration is determined by the stabiUty of the cationic intermediates. Product stereochemistry is under substrate control and usually leads to the thermodynamically more stable THP product. Catalytic variations generally involve palladium complexes [44], but other transition metals are becoming more common (e.g., Pt [45], Ag [46], Sn [47], Ce [48]). The oxidation state of Pd determines the catalyst reactivity. Palladium(O) complexes are nucleophilic and participate in tetrahydropyran synthesis through jt-allyl cation intermediates, whereas Pd(II) complexes possess electrophilic character and progress through a reversible t-complex. 

Complete reduction to the alkane occurs when palladium on carbon (Pd/C) is used as catalyst, but hydrogenation can be stopped at the alkene if the less active Lindlar catalyst is used. The Lindlar catalyst is a finely divided palladium metal that has been precipitated onto a calcium carbonate support and then deactivated by treatment with lead acetate and quinoline, an aromatic amine. The hydrogenation occurs with syn stereochemistry (Section 7.5), giving a cis alkene product. 

Thus far, chemists have been able to influence the stereoselectivity of macro-cyclic RCM through steric and electronic substrate features or by the choice of a catalyst with appropriate activity, but there still exists a lack of prediction over the stereochemistry of macrocyclic RCM. One of the most important extensions of the original metathesis reaction for the synthesis of stereochemi-cally defined (cyclo)alkenes is alkyne metathesis, followed by selective partial hydrogenation. 

In 1995, and regrettably missed in last year s review, Klotgen and Wiirthwein described the formation of the 4,5-dihydroazepine derivatives 2 by lithium induced cyclisation of the triene 1, followed by acylation <95TL7065>. This work has now been extended to the preparation of a number of l-acyl-2,3-dihydroazepines 4 from 3 <96T14801>. The formation of the intermediate anion and its subsequent cyclisation was followed by NMR spectroscopy and the stereochemistry of the final product elucidated by x-ray spectroscopy. The synthesis of optically active 2//-azepines 6 from amino acids has been described <96T10883>. The key step is the cyclisation of the amino acid derived alkene 5 with TFA. These azepines isomerise to the thermodynamically more stable 3//-azepines 7 in solution. 

Both the olefin stereochemistry observed and the results of cross-over experiments (added m-chlorobenzaldehyde) confirm the faster rate of reversibility (to ylide and aldehyde) of cis-(34) compared to trans-(34) and indicate that this difference is greater than earlier work had suggested. Even more interesting is the observation of a synergistic effect (leading to excessively enhanced amounts of (E)-alkene) when deliberately prepared mixtures of ervthro- and threo-(33) are decomposed. The volumes of activation... 

The most famous mechanism, namely Cossets mechanism, in which the alkene inserts itself directly into the metal-carbon bond (Eq. 5), has been proposed, based on the kinetic study [134-136], This mechanism involves the intermediacy of ethylene coordinated to a metal-alkyl center and the following insertion of ethylene into the metal-carbon bond via a four-centered transition state. The olefin coordination to such a catalytically active metal center in this intermediate must be weak so that the olefin can readily insert itself into the M-C bond without forming any meta-stable intermediate. Similar alkyl-olefin complexes such as Cp2NbR( /2-ethylene) have been easily isolated and found not to be the active catalyst precursor of polymerization [31-33, 137]. In support of this, theoretical calculations recently showed the presence of a weakly ethylene-coordinated intermediate (vide infra) [12,13]. The stereochemistry of ethylene insertion was definitely shown to be cis by the evidence that the polymerization of cis- and trans-dideutero-ethylene afforded stereoselectively deuterated polyethylenes [138]. 

Attempts to control the stereochemistry of the addition of chlorine to alkenes using ephedrinium and cinchoninium salts give only low optical activity [31]. 

The final stereochemistry of a metathesis reaction is controlled by the thermodynamics, as the reaction will continue as long as the catalyst is active and eventually equilibrium will be reached. For 1,2-substituted alkenes this means that there is a preference for the trans isomer the thermodynamic equilibrium at room temperature for cis and trans 2-butene leads to a ratio 1 3. For an RCM reaction in which small rings are made, clearly the result will be a cis product, but for cross metathesis, RCM for large rings, ROMP and ADMET both cis and trans double bonds can be made. The stereochemistry of the initially formed product is determined by the permanent ligands on the metal catalyst and the interactions between the substituents at the three carbon atoms in the metallacyclic intermediate. Cis reactants tend to produce more cis products and trans reactants tend to give relatively more trans products this is especially pronounced when one bulky substituent is present as in cis and trans 4-methyl-2-pentene [35], Since the transition states will resemble the metallacyclobutane intermediates we can use the interactions in the latter to explain these results. 

The major focus in this chapter will be on synthesis, with emphasis placed on more recent applications, particularly those where regiochemistry and stereochemistry are precisely controlled. The reader is referred to the earlier reviews for full mechanistic information and details of historic interest. Electrophilic addition of X—Y to an alkene, where X is the electrophile, gives products with functionality Y (3 to the heteroatom X. Further transformations of X and/or Y provide the basis for diverse synthetic applications. These transformations include replacement of Y by hydrogen, elimination to form a ir-bond (either including the carbon bonded to X or (3 to that carbon so that X is now in an allylic position), and nucleophilic or radical substitution. Representative examples of these synthetic methods will be given below. This chapter will include examples of heterocycles formed in one-pot reactions where the the initial alkene-electrophile adduct contains an electrophilic group that can react further. Examples of heterocycles formed in several steps from alkene-electrophile adducts will also be considered. Cases in which activation by an external electrophile directly results in addition of an internal heteroatom nucleophile are treated in Chapter 1.9 of this volume. 

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