Stereochemistry determining

Addition of hydride ion from the catalyst gives the adsorbed dianion (15). The reaction is completed and product stereochemistry determined by protonation of these species from the solution prior to or concurrent with desorption. With the heteroannular enolate, (13a), both cis and trans adsorption can occur with nearly equal facility. When an angular methyl group is present trans adsorption (14b) predominates. Protonation of the latter species from the solution gives the cis product. Since the heteroannular enolate is formed by the reaction of A" -3-keto steroids with strong base " this mechanism satisfactorily accounts for the almost exclusive formation of the isomer on hydrogenation of these steroids in basic media. The optimum concentration of hydroxide ion in this reaction is about two to three times that of the substrate. 

Iodine azide, generated in situ from an excess of sodium azide and iodine monochloride in acetonitrile, adds to ethyl l//-azepine-l-carboxylate at the C4 — C5 and C2 —C3 positions to yield a 10 1 mixture of the rw-diazidodihydro-l//-azepines 1 and 2, respectively.278 The as stereochemistry of the products is thought to be the result of initial trans addition of the iodine azide followed by an SN2 azido-deiodination. The diazides were isolated and their stereochemistry determined by conversion to their bis-l,3-dipolar cycloadducts with dimethyl acetylene-dicarboxylate. 

B uilding on the original proposal by Yates, the mechanism of this reaction is believed to involve the formation of copper carbenoids as intermediates, Scheme 1. Beyond the fact that copper, its ligands, the carbenoid fragment, and alkene are involved in the stereochemistry-determining event, as evidenced by Noyori et al. (2) and later by Moser (11, 12), little definitive mechanistic information has been acquired for this process. The basics of the mechanism will be discussed in this section. In subsequent sections detailing enantioselective variants, specific factors that have added to the understanding of this reaction will be addressed as will the models used to rationalize the observed stereochemistry. 

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. 

Andrus et al. (109) proposed a stereochemical rationale for the observed selec-tivities in this reaction. The model is based on the Beckwith modification (97) of the Kochi mechanism, suggesting that the stereochemistry-determining event is the ally lie transposition from Cu(III) allyl benzoate intermediates 152 and 153, Fig. 13. Andrus suggests that the key Cu(III) intermediate assumes a distorted square-planar geometry. Steric interactions are decreased between the ligand substituent and the cyclohexenyl group in Complex 152 as opposed to Complex 153 leading to the observed absolute stereochemistry. 

Nakajima et al. (129) suggests that the stereochemistry is determined via intermediate 188 (Fig. 14). Unfortunately, nonlinear effects (78), which might be expected to shed light on the involvement of 2 equiv of ligand metal complex in the stereochemistry-determining event, were not examined in this system. 

Whether this is due to the intervention of more than one ligand-containing species in the stereochemistry-determining event or differential kinetic stabilities of diastereomeric trimers is not clear. 

Conjugate Addition Reaction 323 rate- and stereochemistry-determining step... 

NB. The Q symbol indicates the stereochemistry determining step Scheme 1 General catalytic cycle for the asymmetric acylation of iec-alcohols [2]... 

Reaction Pathway. The simplest pathway is illustrated by the /3-keto ester substrate in Scheme 50. As suggested by reaction with RuCl2[P(C6H5)3]3 as the catalyst precursor (40c, 96), this hydrogenation seems to occur by the monohydride mechanism. The catalyst precursor has a polymeric structure but perhaps is dissociated to the monomer by alcoholic solvents. Upon exposure to hydrogen, RuC12 loses chloride to form RuHCl species A, which, in turn, reversibly forms the keto ester complex B. The hydride transfer in B, from die Ru center to the coordinated ketone to form C, would be the stereochemistry-determining step. Liberation of the hydroxy ester is facilitated by the al-... 

Solution-state NMR studies suggest that the catalysts containing l- and D-Pro adopt p-turns and p-hairpins in solution,respectively. Reactions exhibit first-order dependence on catalyst 24, consistent with a monomeric catalyst in the ratedetermining step of the reaction. These catalysts exhibit enantiospecific rate acceleration, in comparison to the reaction rate when NMI is employed as catalyst. An isosteric replacement of an alkene for a backbone amide in a tetrapeptide catalyst (catalysts 32 and 33, Fig. 4) has lent credence to a proposed mechanism of rate acceleration [31). While catalyst 32 exhibits a fcrei=28 with substrate 27, alkene-containing catalyst 33 is not selective in this kinetic resolution and also affords a reduced reaction rate. This suggests that the prolyl amide is kinetically significant in the stereochemistry-determining step of the reaction. 

As in the AD, cinchona alkaloids are utilized as ligands in the AA. Because the face selectivities in these two processes are identical, it was concluded that the stereochemistry-determining steps should be identical or at least closely related with each other. Predictions of the absolute configurations of the amino alcohols obtained by AA can, therefore, be made by using the same mnemonic device as given for the AD (see Section 6D.1). 

The first investigations by Bryce-Smith et al. [46,67,153] on ortho photocycloaddition of an alkene to hexafluorobenzene have revealed yet another secondary reaction of ortho photocycloadducts. Irradiation of a solution of hexafluorobenzene in r/.v-cyclooctene leads to the rapid formation of seven adducts of which six were identified (i) the exo-meta adduct, (ii) a product that can be formed from the meta adduct by a thermal 1,5 H-shift but which apparently is also a primary product, (iii) an ortho adduct of which the configuration could not be established, (iv) a cyclooctatriene derivative formed by thermal ring opening of the ortho adduct, and (v) and (vi) two stereoisomers of 2,3,4,5,6,7-hexaflu-orotetracyclo[6.6.0.02,7.03,6]tetradec-4-ene. The experiment was repeated 9 years later by Sket et al. [151] with the important difference that cyclohexane was used as a diluent. The meta adduct (i) and its formal rearrangement product (ii) were not found. One ortho adduct (iii), the cyclooctatriene (iv), and the two tetracyclic products (v) and (vi) could be identified and their stereochemistry determined. From their results, the authors concluded that a second ortho adduct with the alternative stereochemistry must also have been formed. They also performed experiments in which the influence of the solvent on the course of the reaction was studied and found that the difference between their results and those of Bryce-... 

We have found that the Michael addition of w-hexyl cuprate to levoglucosenone (2) gives the exo adduct 7 (stereochemistry determined by NOE lH NMR spectroscopy) as the major product in 70-80% yield less than... 

The proposed mechanism for this catalytic asymmetric hydrophosphonylation is shown in Figure 35. The first step of this reaction is the deprotonation of dimethyl phosphite by LPB to generate potassium dimethyl phosphite. This potassium phosphite immediately coordinates to a lanthanoid to give I due to the strong oxophilicity of lanthanoid metals. The complex I then reacts (in the stereochemistry-determining step) with an imine to give the potassium salt of the a-aminophosphonate. A proton-exchange reaction affords the product... 

The 191 problems in this book cover most of the area of stereochemistry, including nomenclature, stereogenic elements (centers, axes, planes) and their descriptors, symmetry, inorganic stereochemistry, determination of enantiomer excess, conformation of acyclic and cyclic compounds, and more. The answers, in addition to providing solutions to the problems, frequently include additional explanations of the underlying principles. The problems are ordered more or less in order of increasing difficulty. (I had a hard time with some of the problems toward the end myself )... 

In early studies, this stereochemistry was established for a select few lantibiotics by comparison to chemically synthesized standards in combination with gas chromatography using chiral stationary phases. The stereochemistry determined in these early studies is assumed to be the same for lantibiotics that were discovered and characterized subsequently, but for most members this supposition has not been confirmed experimentally. 

Examples are known in which first the Michael adducts (207) are formed and isolated followed by cyclization in a separate step in the presence of base (equation 56)" . The stereochemistry-determining step is the cyclization of the intermediate carbanion as illustrated below. There are two favoured conformations, I and II, of the carbanion-cation... 

On the other hand, 1,4-addition must involve a diadsorbed sp)ecies such as 64. The surface atoms can be MH, MH, or 3mH2, but only one can be the MH2 type. The transfer of one hydrogen atom from each surface site gives the adsorbed olefin with its stereochemistry determined by the mode of adsorption of the diene. The s-cis form of butadiene (65) is about 2.3 kcal/mol less stable than the s-trans form (66). This corresponds to about a 30 70 ratio, which agrees quite well with the observed cis/trans-2-butene ratios formed over Type B catalysts. The likelihood of 1,4-addition is increased when larger catalyst particles are present because more neighboring edge and comer atoms are also present. 

A new marine fungal, tentatively identified as Fusarium heterosporum, produced a series of compounds with spirotricyclic framework, mangicols A-G 1-7 The stereochemistry determination of 1 was based on spectral data from both the natural product and derivatives synthesized. The mangicols 1-7 showed only weak to modest... 

In the reduction of alkynes to trans alkenes, the second electron transfer occurs after the first protonation. The stereochemistry-determining step is protonation of the carbanion obtained after the second electron transfer. The thermodynamically more stable trans product is obtained. 

The observed activation of allyltrihalosilanes with fluoride ion and DMF and the proposition that these agents are bound to the silicon in the stereochemistry-determining transition structures clearly suggested the use of chiral Lewis bases for asymmetric catalysis. The use of chiral Lewis bases as promoters for the asymmetric allylation and 2-butenylation of aldehydes was first demonstrated by Denmark in 1994 (Scheme 10-31) [55]. In these reactions, the use of a chiral phos-phoramide promoter 74 provides the homoallylic alcohols in high yield, albeit modest enantioselectivity. For example, the ( )-71 and benzaldehyde affords the anti homoallylic alcohol 75 (98/2 antUsyn) in 66% ee. The sense of relative stereoinduction clearly supports the intermediacy of a hexacoordinate silicon species. The stereochemical outcome at the hydroxy center is also consistent with a cyclic transition structure. 

Isolated yields. Enantiomeric excesses of the allylated product were determined by chiral HPLC analysis. Absolute stereochemistry determined to be (JR) by CD spectrum of 2-methyl-2-propyl-4-methoxyindanone. 

Diastereoselective cyclizations are possible [73], in particular when the outcome of the stereochemistry is set by the configuration of a cylic ring junction (Fig. 10). The stereochemistry-determining insertion step proceeds via the less encumbered transition state providing a single diastereoisomer. 

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