Hydride-ion capture

A second method for the preparation of 1,2-dialkylidenecycloalkanes 83 starts from 2-bromoenynes 79 and comprises a hydride ion capture by an initially formed cr-alkenylpalladium species (a reductive Heck reaction) [62]. Good results were obtained for the preparation of five-membered rings, but the yields seriously dropped when going to the next higher homologues with n = 6, and no sequences including subsequent [4 + 2] cycloadditions have been reported to date. 

Heck reactions with subsequent reduction ( hydride-ion capture ) [103, 105, 192] also have become valuable methods for the construction of various carbo- and heterocyclic skeletons. Such a reaction comes about when the. syn-addition of an aryl- or alkenylpalladium species to a multiple bond leads to an intermediate which does not or cannot undergo a rapid 5yn-jS-hydride elimination (Scheme 3-41) [105] (cf. [71b]. 

Burns, B., Grigg, R., Santhkumar, V. eta/. (1992) Palladium catalysed tandem cyclisation anion capture and hydride ion capture by alkyl- and 7T-allyl-palladium species. Tetrahedron, 48, 7297-320. 

Bums, B., Grigg, R., Sridharan, V. and Worakun, T. (1988) Palladium catalysed tandem cycUsation-anion capture processes. Hydride ion capture by vinylpalladium species. Tetrahedron Lett., 29, 4325-8. 

Methylcyclohexane and acyclic isoalkanes are better hydride donors than the methylcyclopentane. Consequently, alkenoyl chlorides are able to do intermolecular hydride ion capture giving cyclopentenones resulting from a Nazarov cyclization. Starred methyl groups undergo migration in the process. Works are in progress in this field. 

The parent ion 5 and its naphtho[6] analogue have been generated by treatment of 1 and 11, respectively, with trityl tetrafluoroborate. The cations so formed are captured by water and the final product of reaction is the ring opened aryl aldehyde (equation 24)230 231. Kinetic measurements have shown230 that abstraction of hydride ion from 1 is first order and displays a deuterium isotope effect of 6.5. To the best of the author s knowledge, the isolation and spectroscopic characterization of an unsubstituted cycloproparenyl cation has yet to be achieved. 

Overall then the Pyruvate DH Complex converts pyruvate into acetyl CoA in a physiologically irreversible reaction with the release of carbon dioxide and the capture of an electron pair as a hydride ion on NADH. Note the cofactors involved for this reaction sequence TPP, FAD, Mg2+, lipoamide. Coenzyme A, and NAD+. 

The rate ratio of the 6,2-hydride shift and of the ion capture by the nucleophile depends greatly on the nature of the substrate and on the reaction conditions. Thus, apoisobornyl brosylate 79 and exo-camphenyl brosylate 80 yield the same relative amount of P-phenchocamphoryl product A in a wide range of media ( 50% in CH3COOH somewhat less in more nucleophilic media)... 

The situation is entirely different in the case of radical anions. These are stabilized in solution by solvation. Their formation by electron capture therefore takes place much more readily in solution than it does in the gas phase and once formed, they are more stable. They are also less reactive than radical cations because they cannot easily lose hydride ions. Spontaneous decomposition can usually occur only if the radical anion contains an atom or group that can easily be expelled as an anion. Thus electron capture by alkyl halides gives rise to radicals and halide ions e.g.,... 

A new kinetic equation to estimate activation energies of various hydride transfer reactions has been developed according to transition state theory by using the Morse-type free energy curves of hydride donors and acceptors to model hydride ion release and capture, respectively. " A perfect unity of the kinetic equation and thermodynamic equation for hydride transfer reactions has been achieved. 

C — C bond scission occurs in the jS-position to the carbenium ion atom. The new carbenium ion may either crack or capture a hydride ion from the alkane molecule. The olefin is more easily converted to a carbenium ion than the initial alkane and cracks... 

Addition begins m the usual way by protonation of the double bond to give m this case a secondary carbocation This carbocation can be captured by chloride to give 2 chloro 3 methylbutane (40%) or it can rearrange by way of a hydride shift to give a tertiary carbocation The tertiary carbocation reacts with chloride ion to give 2 chloro 2 methylbutane (60%)... 

An alternative view of these addition reactions is that the rate-determining step is halide-assisted proton transfer, followed by capture of the carbocation, with or without rearrangement Bromide ion accelerates addition of HBr to 1-, 2-, and 4-octene in 20% trifluoroacetic acid in CH2CI2. In the same system, 3,3-dimethyl-1-butene shows substantial rearrangement Even 1- and 2-octene show some evidence of rearrangement, as detected by hydride shifts. These results can all be accoimted for by a halide-assisted protonation. The key intermediate in this mechanism is an ion sandwich. An estimation of the fate of the 2-octyl cation under these conditions has been made ... 

Another useful route to alkaloids involves the electrochemical oxidation of lactams (145) bearing functionality on nitrogen that can be used to intramolec-ularly capture an intermediate acyl im-minium ion (146). The concept is portrayed in Scheme 33 and is highlighted by the synthesis of alkaloids lupinine (150) and epilupinine (151) shown in Scheme 34 [60]. Thus, the electrooxidation of lactam (147) provided a 71% yield of ether (148). Subsequent treatment with titanium tetrachloride affected cyclization and afforded the [4.4.0] bicyclic adduct (149). Krapcho decarbomethoxylation followed by hydride reduction of both the... 

Before we turn to other investigations of the stabilized ion it is interesting briefly to compare the rates of hydride shifts found in the strong acid systems with rates obtained under solvolytic conditions. Collins and Lietzke (1967) and Berson et al. (1967) have deduced the rates of 3,2- and 6,2-hydrogen migration relative to the rate of solvent capture for norbornyl ions in acetic acid, formic acid and other common solvents from elaborate C scrambling studies due to Roberts and Lee (1951) and Roberts et al., (1954) and tritium labelling studies of Lee and Lam (1966). From the ratio of these... 

Protonation of 3-methyl-2-butanol and dissociation of the alkyloxonium ion gives a secondary carbocation. A hydride shift yields a tertiary, and thus more stable, carbocation. Capture of this car-bocation by chloride ion gives the major product, 2-chloro-2-methylbutane. 

An enamine intermediate has been proposed as being formed by hydride reduction of a transient iminium ion [14, 15]. The electrophilic capture of the enamine is possible by a Michael acceptor thus, reductive Michael cyclizations of enal enones such as 9 or 11 were described in many cases (intramolecular reactions) (Scheme 11.5) [16]. 

The utility of cationic surfactants in increasing hydride transfer would be expected to be shown by an Increased yield of octanes during butene alkylation. This follows if alkylate selectivity is decided by the ratio of the rate at which intermediate Ions are captured by hydride transfer to the rate at which they add to olefins and polymerize, and If the effect of the additives Is to selectively raise the specific rate constant for hydride transfer, kg". 

Terpene synthases, also known as terpene cyclases because most of their products are cyclic, utilize a carbocationic reaction mechanism very similar to that employed by the prenyltransferases. Numerous experiments with inhibitors, substrate analogues and chemical model systems (Croteau, 1987 Cane, 1990, 1998) have revealed that the reaction usually begins with the divalent metal ion-assisted cleavage of the diphosphate moiety (Fig. 5.6). The resulting allylic carbocation may then cyclize by addition of the resonance-stabilized cationic centre to one of the other carbon-carbon double bonds in the substrate. The cyclization is followed by a series of rearrangements that may include hydride shifts, alkyl shifts, deprotonation, reprotonation and additional cyclizations, all mediated through enzyme-bound carbocationic intermed iates. The reaction cascade terminates by deprotonation of the cation to an olefin or capture by a nucleophile, such as water. Since the native substrates of terpene synthases are all configured with trans (E) double bonds, they are unable to cyclize directly to many of the carbon skeletons found in nature. In such cases, the cyclization process is preceded by isomerization of the initial carbocation to an intermediate capable of cyclization. 

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