Stereochemistry reductive elimination

The stereochemistry of the Pd-catalyzed allylation of nucleophiles has been studied extensively[5,l8-20]. In the first step, 7r-allylpalladium complex formation by the attack of Pd(0) on an allylic part proceeds by inversion (anti attack). Then subsequent reaction of soft carbon nucleophiles, N- and 0-nucleophiles proceeds by inversion to give 1. Thus overall retention is observed. On the other hand, the reaction of hard carbon nucleophiles of organometallic compounds proceeds via transmetallation, which affords 2 by retention, and reductive elimination affords the final product 3. Thus the overall inversion is observed in this case[21,22]. 

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

Disulfonate esters of vicinal diols sometimes undergo reductive elimination on treatment with sodium iodide in acetone at elevated temperature and pressure (usually l(X)-200°). This reaction derived from sugar chemistry has been used occasionally with steroids, principally in the elimination of 2,3-dihy-droxysapogenin mesylates. The stereochemistry of the substituents and ring junction is important, as illustrated in the formation of the A -olefins (133) and (134). 

The success of the halo ketone route depends on the stereo- and regio-selectivity in the halo ketone synthesis, as well as on the stereochemistry of reduction of the bromo ketone. Lithium aluminum hydride or sodium borohydride are commonly used to reduce halo ketones to the /mm-halohydrins. However, carefully controlled reaction conditions or alternate reducing reagents, e.g., lithium borohydride, are often required to avoid reductive elimination of the halogen. 

Secondary bromides and tosylates react with inversion of stereochemistry, as in the classical SN2 substitution reaction.24 Alkyl iodides, however, lead to racemized product. Aryl and alkenyl halides are reactive, even though the direct displacement mechanism is not feasible. For these halides, the overall mechanism probably consists of two steps an oxidative addition to the metal, after which the oxidation state of the copper is +3, followed by combination of two of the groups from the copper. This process, which is very common for transition metal intermediates, is called reductive elimination. The [R 2Cu] species is linear and the oxidative addition takes place perpendicular to this moiety, generating a T-shaped structure. The reductive elimination occurs between adjacent R and R groups, accounting for the absence of R — R coupling product. 

The mechanism for the reaction catalyzed by cationic palladium complexes (Scheme 24) differs from that proposed for early transition metal complexes, as well as from that suggested for the reaction shown in Eq. 17. For this catalyst system, the alkene substrate inserts into a Pd - Si bond a rather than a Pd-H bond [63]. Hydrosilylation of methylpalladium complex 100 then provides methane and palladium silyl species 112 (Scheme 24). Complex 112 coordinates to and inserts into the least substituted olefin regioselectively and irreversibly to provide 113 after coordination of the second alkene. Insertion into the second alkene through a boat-like transition state leads to trans cyclopentane 114, and o-bond metathesis (or oxidative addition/reductive elimination) leads to the observed trans stereochemistry of product 101a with regeneration of 112 [69]. 

Insertion of palladium into the Si-Sn bond generates intermediate 428 that undergoes m-addition on the triple bond (Scheme 108). The resulting vinylpalladium 429 ensures the carbopalladation of the second triple bond followed by reductive elimination with retention of stereochemistry.376... 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

Although the reaction of a titanium carbene complex with an olefin generally affords the olefin metathesis product, in certain cases the intermediate titanacyclobutane may decompose through reductive elimination to give a cyclopropane. A small amount of the cyclopropane derivative is produced by the reaction of titanocene-methylidene with isobutene or ethene in the presence of triethylamine or THF [8], In order to accelerate the reductive elimination from titanacyclobutane to form the cyclopropane, oxidation with iodine is required (Scheme 14.21) [36], The stereochemistry obtained indicates that this reaction proceeds through the formation of y-iodoalkyltitanium species 46 and 47. A subsequent intramolecular SN2 reaction produces the cyclopropane. 

Evans suggests that the catalyst resting state in this reaction is a 55c Cu alkene complex 58, Scheme 4 (35). Variable temperature NMR studies indicate that the catalyst complexes one equivalent of styrene which, in the presence of excess alkene, undergoes ready alkene exchange at ambient temperature but forms only a mono alkene-copper complex at -53°C. Addition of diazoester fails to provide an observable complex. These workers invoke the metallacyclobutane intermediate 60 via a formal [2 + 2] cycloaddition from copper carbenoid alkene complex 59. Formation of 60 is the stereochemistry-determining event in this reaction. The square-planar S Cu(III) intermediate 60 then undergoes a reductive elimination forming the cyclopropane product and Complex 55c-Cu, which binds another alkene molecule. 

This reaction probably proceeds via the neutral hydride that undergoes reductive elimination of germane. The stereochemistry observed (retention of configuration) is in agreement with a reductive elimination and with the assumption that the formation of the molybdenum-germanium bond proceeds with retention of configuration (cf. Sect. 3.1.2). 

The stereochemistry of 338 and 339 in each case results from initial conjugate addition of MeO" at position 2 of the chromone ring. Ensuing attack of the formed enolate 342 upon PhI(OMe)2 occurs in an anti manner because of steric interaction. Sequential addition of MeO to the carbonyl group of 343 gives 344, and intramolecular reductive elimination of C6H5I then occurs with inversion of configuration, 344 345. The reaction is... 

Whether this condition can be fulfiUed depends on the electron count of the metal, and the stereochemistry of the elimination. For instance, in m-elimination from octahedral d , or square planar d , systems, metal ndipP -y ) acts as acceptor, and this should be a facile process ( e Fip. 1, 2). For /rans-elimination, on tiie other hand, the lowest empty orbital of correct symmetry is (n + l)p. Such elimination Kerns energetically less Ukely, unless a non-concerted pathway (such as successive anionic and cationic loss) is available. The same arguments apply, of course, to oxidative additions. It foUows that the many known cases of traits oxidative addition to square planar t/ systems are unlikely to take place by a concerted mechanism, and this conclusion is now generally accepted There are special complexities in reductive elimination from trigonal systems, and these are discussed furdier in Part III. 

If, however, the catalytic hydrogenolysis of a 2,6-dibromohexonolactone was performed with no acid acceptor present, an unusual reduction took place to give a 6-bromo-2,3,6-trideoxyhexonolactone. Thus, 2 gave 6-bromo-2,3,6-tri-deoxy-D-eryfhro-hexonolactone (1) (Scheme 2) [35]. Similar reductions took place with other hexono- and pentonolactones independent of the relative stereochemistry of the C-2 and C-3 substituents [35]. A 7-bromo-2,3,7-tri-deoxyheptonolactone has also been synthesized in this way [22]. The initial step in the reactions was shown to be a reductive elimination to give an intermediate 2,3-unsaturated lactone which subsequently was saturated [35]. 

Mori has reported the nickel-catalyzed cyclization/hydrosilylation of dienals to form protected alkenylcycloalk-anols." For example, reaction of 4-benzyloxymethyl-5,7-octadienal 48a and triethylsilane catalyzed by a 1 2 mixture of Ni(GOD)2 and PPhs in toluene at room temperature gave the silyloxycyclopentane 49a in 70% yield with exclusive formation of the m,//7 //i -diastereomer (Scheme 14). In a similar manner, the 6,8-nonadienal 48b underwent nickel-catalyzed reaction to form silyloxycyclohexane 49b in 71% yield with exclusive formation of the // /i ,// /i -diastereomer, and the 7,9-decadienal 48c underwent reaction to form silyloxycycloheptane 49c in 66% yield with undetermined stereochemistry (Scheme 14). On the basis of related stoichiometric experiments, Mori proposed a mechanism for the nickel-catalyzed cyclization/hydrosilylation of dienals involving initial insertion of the diene moiety into the Ni-H bond of a silylnickel hydride complex to form the (7r-allyl)nickel silyl complex li (Scheme 15). Intramolecular carbometallation followed by O-Si reductive elimination and H-Si oxidative addition would release the silyloxycycloalkane with regeneration of the active silylnickel hydride catalyst. 

Figure 8.5 Catalytic cycle for the metal-catalyzed carbonylation of methanol, with the reductive elimination step highlighted. In the case of iridium, the diiodotricarbonyl species has also been suggested as a possible precursor to reductive elimination. What aie the issues of stereochemistry associated with the intermediates What special basis-set requirements will be involved in modeling this system ...

In this generic example, the oxidation state of the metal is reduced by two, while the product is released in the reductive elimination step. In many reactions the oxidative addition does not provide the proper stereochemistry for elimination an isomerization must occur. 

Oxidation of alkyl iodides, bearing electron-withdrawing groups such as car-bomethoxy and sulfonyl at the a-carbon, with m-chloroperbenzoic acid results in clean elimination to give olefins [Eq. (27)]. This reaction involves reductive / -elimination of the intermediate iodosylalkanes, as observed in thermal peri-cyclic -elimination of sulfoxides and selenoxides. Exclusive syn stereochemistry in the reductive /1-elimination was established by deuterium labeling... 

At ambient temperatures and in neat CH3I as a solvent, IR bands and NMR signals for complexes 4.2-4.4 are seen. The stereochemistry of 4.2 as shown in the catalytic cycle is consistent with the spectroscopic data. The relative thermodynamic and kinetic stabilities of complexes 4.1-4.3 under these conditions have also been estimated. The data show that 4.2 is unstable with respect to conversion to both 4.3 and 4.1. In other words, 4.2 undergoes facile insertion and reductive elimination reactions. 

The Mechanism of the cross coupling reaction can be accommodated by an oxidative addition of 1-bromopropene to iron(l) followed by exchange with ethylmagnesium bromide and reductive elimination. Scheme 3 is intended to form a basis for discussion and further study of the catalytic mechanism. In order to maintain the stereospecificity, the oxidative addition of bromo-propene in step a should occur with retention. Similar stereochemistry has been observed in oxidative additions of platinum(O) and nickel(O) complexes.(32)(33) The metathesis of the iron(lll) intermediate in step b is ixp icted to be rapid in analogy with other alkylations.(34) The formation of a new carbon-carbon bond by the redilcTive elimination of a pair of carbon-centered ligands in step c has been demonstrated to occur... 

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