Selective insertion reactions

Woerpel and Nevarez demonstrated the synthetic potential of silaaziridines by selective insertion reactions (Scheme 7.52).123 Silver-catalyzed aldehyde insertion into the Si-N bond of 169b produced the N,0-cyclic acetal 180 as the cis isomer. In contrast to this process, insertion of tert-butyl isocyanide occurred into the weaker C-Si bond to afford imine 181. The authors rationalized the chemoselectivity for these two processes on the basis of Pearson s hard-soft acid-base theory 124-126 the more ionic Si-N bond reacted with harder benzaldehyde electrophile, whereas the more covalent Si-C bond reacted with the softer isocyanide. 

This conceptual link extends to surfaces that are not so obviously similar in stmcture to molecular species. For example, the early Ziegler catalysts for polymerization of propylene were a-TiCl. Today, supported Ti complexes are used instead (26,57). These catalysts are selective for stereospecific polymerization, giving high yields of isotactic polypropylene from propylene. The catalytic sites are beheved to be located at the edges of TiCl crystals. The surface stmctures have been inferred to incorporate anion vacancies that is, sites where CL ions are not present and where TL" ions are exposed (66). These cations exist in octahedral surroundings, The polymerization has been explained by a mechanism whereby the growing polymer chain and an adsorbed propylene bonded cis to it on the surface undergo an insertion reaction (67). In this respect, there is no essential difference between the explanation of the surface catalyzed polymerization and that catalyzed in solution. 

The thermodynamic properties of to-potactic insertion reaction materials with selective equilibrium are quite different from those of materials in which complete equilibrium can be assumed, and reconstitution reactions take place. Instead of flat plateaus related to polyphase equilibria, the composition-dependence of the potential generally has a flat S-type form. 

With nonracemic chiral diazoacetates the insertion process occurs with evident match/mismatch characteristics. This has been demonstrated in reactions of optically pure 2-methylcyclohexyl diazoacetates (Eq. 9) [85] and in carbon-hydrogen insertion reactions of steroidal diazoacetates (Eq. 10) [86], as well as with the synthesis of pyrrolizidines 36 and 37 [84]. The mechanistic preference for formation of a /J-lactone in Eq. 10 over insertion into the 4-position is not clear,but there are other examples of /J-lactone formation [87]. In these and related examples, selectivities in match/mismatch examples are high, and future investigations are anticipated to show even greater applicability. 

One of the most dramatic recent developments in metal carbene chemistry catalyzed by dirhodium(II) has been demonstration of the feasibility and usefulness of intermolecular carbon-hydrogen insertion reactions [38, 91]. These were made possible by recognition of the unusual reactivity and selectivity of aryl- and vinyldiazoacetates [12] and the high level of electronic control that is possible in their reactions. Some of the products that have been formed in these reactions, and their selectivities with catalysis by Rh2(S-DOSP)4, are reported in Scheme 10. 

The highly reactive species methylene inserts into C—H bonds,both aliphatic and aromatic,though with aromatic compounds ring expansion is also possible (see 15-62). This version of the reaction is useless for synthetic purposes because of its nonselectivity (see p. 248). This contrasts with the metal carbene insertion reaction, which can be highly selective, and is very useful in synthesis. Alkylcarbenes usually rearrange rather than give insertion (p. 249), but, when this is impossible. 

There are numerous examples of metal carbene insertion reactions, usually requiring a catalyst. " The C—H insertion reactions of metal carbenes can be highly selective. Intramolecular insertion reactions are very versatile and tolerate a... 

Carbene itself is extremely reactive and gives many side reactions, especially insertion reactions (12-19), which greatly reduce yields. When it is desired to add CH2 for preparative purposes, free carbene is not used, but the Simmons-Smith procedure (p. 1088) or some other method that does not involve free carbenes is employed instead. Halocarbenes are less active than carbenes, and this reaction proceeds quite well, since insertion reactions do not interfere.The absolute rate constant for addition of selected alkoxychlorocarbene to butenes has been measured to range from 330 to 1 x 10 A few of the many ways in... 

The subjects of structure and bonding in metal isocyanide complexes have been discussed before 90, 156) and will not be treated extensively here. A brief discussion of this subject is presented in Section II of course, special emphasis is given to the more recent information which has appeared. Several areas of current study in the field of transition metal-isocyanide complexes have become particularly important and are discussed in this review in Section III. These include the additions of protonic compounds to coordinated isocyanides, probably the subject most actively being studied at this time insertion reactions into metal-carbon bonded species nucleophilic reactions with metal isocyanide complexes and the metal-catalyzed a-addition reactions. Concurrent with these new developments, there has been a general expansion of descriptive chemistry of isocyanide-metal complexes, and further study of the physical properties of selected species. These developments are summarized in Section IV. 

Few quantitative data are available on the relative nucleophilicities of L toward various alkyl carbonyls. The rates of the reaction of CpMo(CO)3Me with L in toluene (Table II) decrease as a function of the latter reactant P( -Bu)3 > P( -OBu)j > PPhj > P(OPh)j, but the spread is relatively small (<8). The above order is that customarily observed for 8 2 reactions of low-valent transition metal complexes (J, 214). Interestingly, neither CpMo(CO)3Me nor CpFe(CO)2Me reacts with 1 or N, S, and As donor ligands 28, 79). This is in direct contrast to the insertion reactions of MeMn(CO)5 which manifest much less selectivity toward various L (see Section VI,B,C,D for details). 

This key paper was followed by a flurry of activity in this area, spanning several years." " "" A variety of workers reported attempts to deconvolute the temperature dependence of carbene singlet/triplet equilibria and relative reactivities from the influence of solid matrices. Invariably, in low-temperature solids, H-abstraction reactions were found to predominate over other processes. Somewhat similar results were obtained in studies of the temperature and phase dependency of the selectivity of C-H insertion reactions in alkanes. While, for example, primary versus tertiary C-H abstraction became increasingly selective as the temperature was lowered in solution, the reactions became dramatically less selective in the solid phase as temperatures were lowered further. Similar work of Tomioka and co-workers explored variations of OH (singlet reaction) versus C-H (triplet reaction) carbene insertions with alcohols as a function of temperature and medium. Numerous attempts were made in these reports to explain the results based on increases in triplet carbene population... 

In recent years, much attention has been focused on rhodium-mediated carbenoid reactions. One goal has been to understand how the rhodium ligands control reactivity and selectivity, especially in cases in which both addition and insertion reactions are possible. These catalysts contain Rh—Rh bonds but function by mechanisms similar to other transition metal catalysts. 

Owing to the high reactivity of the intermediates involved, intermolecular carbene insertion reactions are not very selective. The distribution of products from the photolysis of diazomethane in heptane, for example, is almost exactly that expected on a statistical basis.211... 

There is some increase in selectivity with functionally substituted carbenes, but it is still not high enough to prevent formation of mixtures. Phenylchlorocarbene gives a relative reactivity ratio of 2.1 1 0.09 in insertion reactions with i-propylbenzene, ethylbenzene, and toluene.212 For cycloalkanes, tertiary positions are about 15 times more reactive than secondary positions toward phenylchlorocarbene.213 Carbethoxycarbene inserts at tertiary C—H bonds about three times as fast as at primary C—H bonds in simple alkanes.214 Owing to low selectivity, intermolecular insertion reactions are seldom useful in syntheses. Intramolecular insertion reactions are of considerably more value. Intramolecular insertion reactions usually occur at the C—H bond that is closest to the carbene and good yields can frequently be achieved. Intramolecular insertion reactions can provide routes to highly strained structures that would be difficult to obtain in other ways. 

Carboalkoxynitrenes are somewhat more selective than the corresponding carbenes, showing selectivities of roughly 1 10 40 for the primary, secondary, and tertiary positions in 2-methylbutane in insertion reactions. 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

For most dienes, 7r-bonds adjacent to quaternary centers do not undergo insertion reactions. One notable exception is 1,5-diene (75) (Scheme 17) [44], For this substrate, the observed selectivity is inconsistent with a chair-like (in this case a trans decalin-like) transition structure (76 top) leading to the insertion product, which is typically seen in diene cyclizations with 70 [36]. 

The main path of the palladium-catalyzed reaction of butadiene is the dimerization. However, the trimerization to form /j-1, 3,6,10-dodeca-tetraene takes place with certain palladium complexes in the absence of a phosphine ligand. Medema and van Helden observed, while studying the insertion reaction of butadiene to 7r-allylpalladium chloride and acetate (32, 37), that the reaction of butadiene in benzene solution at 50°C using 7r-allylpalladium acetate as a catalyst yielded w-1,3,6,10-dodecatetraene (27) with a selectivity of 79% at a conversion of 30% based on butadiene in 22 hours. 

Among typical carbon-carbon bond (C-C) formation reactions with carbenes, the cyclopropanation reaction with olefins has been well studied including its application to industrial processes. The second typical reaction of carbenes is the insertion reaction into the carbon-hydrogen bond (C-H) which seems to be a direct and efficient C-C bond forming reaction. However, its use for synthetic purpose has often been limited due to low selectivity of the reactions.3... 

Most of the carbenes examined in this study have more or less a carbenoid nature because they are generated from halogenated precursors and strong base. In this regard, it still remains as an intriguing problem to verify experimentally the higher electrophilicity and selectivity of carbenoids41,42 in comparison to those of free carbenes in the insertion reaction. 

The reaction can be extended to more elaborate systems as shown in the reactions of the substituted pyrrolidines (Equations (25) and (26)).85,86 Even though the 2-substituted pyrrolidine 8 has three electronically activated sites, two are sterically crowded. Furthermore, the Rh2(5-DOSP)4-catalyzed C-H insertion exhibited extreme stereodifferentiation, such that only one enantiomer of 8 was reactive under the reaction conditions. Consequently, a high level of kinetic resolution was observed, and the C-H insertion product was produced with 98% ee (Equation (25)).85 Similar reactivity was seen in the reaction of the 3-substituted pyrrolidine 9. In some regards, this reaction is even more impressive, because there was selective insertion into one of the two available methylene groups adjacent to nitrogen (Equation (26)).85... 

Activation of a C-H bond requires a metallocarbenoid of suitable reactivity and electrophilicity.105-115 Most of the early literature on metal-catalyzed carbenoid reactions used copper complexes as the catalysts.46,116 Several chiral complexes with Ce-symmetric ligands have been explored for selective C-H insertion in the last decade.117-127 However, only a few isolated cases have been reported of impressive asymmetric induction in copper-catalyzed C-H insertion reactions.118,124 The scope of carbenoid-induced C-H insertion expanded greatly with the introduction of dirhodium complexes as catalysts. Building on initial findings from achiral catalysts, four types of chiral rhodium(n) complexes have been developed for enantioselective catalysis in C-H activation reactions. They are rhodium(n) carboxylates, rhodium(n) carboxamidates, rhodium(n) phosphates, and < // < -metallated arylphosphine rhodium(n) complexes. 

Iridium hydride complexes effectively catalyze addition of nitriles or 1,3-dicarbonyl compounds (pronucleophiles) to the C=N triple bonds of nitriles to afford enamines.42S,42Sa Highly chemoselective activation of both the a-C-H bonds and the C=N triple bonds of nitriles has been observed (Equation (72)). To activate simple alkane dinitriles, IrHs(P1Pr3)2 has proved to be more effective (Equation (73)). The reaction likely proceeds through oxidative addition of the a-C-H bonds of pronucleophiles to iridium followed by selective insertion of the CN triple bonds to the Ir-C bond. 

To investigate this idea, which would confirm and summarize a large class of widely accepted mechanisms, the insertion reactions of (Z)- and (E)-butene with catalytic systems based on the C2-symmetric Me2Si(l-Ind)2 ligand and on the ((-symmetric Me2Si(Cp)(9-Flu) ligand have been recently studied. A double approach based on combined quantum mechanics/molecular mechanics (QM/MM) techniques and on selected ethene/2-butene copolymerization runs has recently been utilized.94... 

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