Anti-3 2’ mode

Similar treatment explains the prevalence of the syw-mode 147>148) in a,y-interaction in Sn2 reactions (Fig. 7.37a). The a,5-interaction (e.g. Sn2 type reaction) is predicted to occur with syw-mode, and a,e-interac-tion with anti-mode (Fig. 7.37b and c). 

The reactivity, site of attack, and stereochemistry of the reactions of a variety of nucleophiles (oxygen, sulfur, nitrogen, organometallic) with anti-and syn-naphthalene 1,2 3,4-dioxides have been studied recently.159 In most cases, di- or tetrasubstituted tetrahydronaphthalene products arising from attack at C-l and C-4 positions in the anti mode are produced. These isomeric diepoxides are excellent intermediates for the preparation of a number of difficulty accessible 1,4-disubstituted naphthalene derivatives. 

However, there are experiments which show that the anti mode can also take place. For instance, changing piperidine for sodium propanethiolate, the trans and cis mesitoates 1 and 93 (R,=CgH2(CH3)2 gave a mixture of syn and anti Sl products (30). Also, Oritani and Overton (34) showed that the reaction of dichlorobenzoates 98 (R=CH3 or C5H11, and X Cl2CeH3CO2 ) with (S)-a-methylbenzylamine gave a mixture of syn and anti 5N2 products (ratio =6 4). 

A complete survey of the SNg" reaction can be found in the review of Magid (23). There are several experiments which clearly show that the syn mode is favored but the anti addition can also take place. The factors which favor the anti mode are not yet completely understood. Nevertheless, there appears to be no doubt that stereoelectronic effects play an important role in these reactions. 

Interestingly, the crystal structures of 8-methoxy-l-naphtonitrile and 8-nitro-1-naphtonitrile have been determined by X-ray analysis by Procter, Britton, and Dunitz (24). The structure of the methoxy derivative corresponds to 61 where the exocyclic C —0 bond is bent inward (toward the nitrile group), the exocyclic C-CN bond is bent outward (away from the methoxy group). The C-C = N bond angle is 174° instead of 180°. A similar observation has been made with 8-nitro-l-naphtonitrile. Crystals of this compound contain two symmetry independent molecules which differ in structure. Both show a bent C CN bond and a short 0—C = N distance Icf. 62), but the orientation of the nitro group is different with the result that in one molecule the 0i—Cii distance is 2.69 A whereas in the other, it is 2.79 A. This analysis is in complete agreement with the theoretical calculations and the experimental results presented above. Thus, it can be concluded that the nucleophilic addition on triple-bond (and the reverse process) is strongly influenced by stereoelectronic effects which favor the anti mode of addition. 

A great deal of experimental results have been rationalized on that basis for instance, compound 284 gives only the olefin 286 via an anti process while the isomer 285 gave a mixture of olefin 286 (syn mode) and 287 (anti mode). 

Eschenmoser and collaborators (28) have reported the base induced fragmentation of a.B-epoxy-tosylhydrazones to produce acetylenic ketones (e.g. 69 71). Interestingly, in this fragmentation, both the triple-bond and molecular nitrogen are produced from the key intermediate 70 via an anti mode. The decarboxylation of nitrobenzisoxazole carboxylate (72) into 2-cyano-5-nitrophenol (73) can also be viewed as a trans-elimination (29, 30). 

The Mn-O-C rods in MOF-73, Mn3(BDC)3-(DEF)2, are constructed from a pair of linked six-coordinate Mn(II) centers [Fig. 20.4.44(a)], One metal center is bound by two carboxylate groups acting in the syn,syn mode, one in the bidentate chelating mode, and a fourth one in the syn,anti mode. The other metal center has four carboxylates bound in the syn,syn mode and two in the syn,anti mode. Each rod is built of corner-linked and edge-linked... 

The cyclization reaction occurs in cyclic as well as in acyclic systems and the attack proceeds in the anti-mode on the double bond5. 

The mercury-promoted amination of double bonds proceeded in an anti mode with >99% diastereoselectivity. By treating (Z)-2-butene with dimethylamine in the presence of mer-cury(II) chloride, the syn-adduct of 1 was obtained, while ( )-2-butene under the same conditions afforded the anti-adduct. However, by treating alkenes with ammonia and mercury salts, only ammonia-mercury complexes were formed8-14,171. 

Both complexes are used in the hydroxylation of double bonds via diacetates or dibenzoates of vicinal diols. The reaction is stereospecific. In anhydrous medium (the Privost reaction [783]), the reaction takes place in the anti mode. In the presence of water (the Woodward modification [783]), the reaction results in a syn addition. The mechanisms of both reactions are shown in the section Hydroxylation of Alkenes and Cycloal-kenes in Chapter 3 see equation 78). 

Hydroxylation, the addition of two hydroxyl groups across double bonds, converts alkenes and cycloalkenes into vicinal dials. Stereochem-ically. the addition may occur in the syn or the anti mode. In open-chain alkenes (with the exception of terminal alkenes for which stereochemistry is irrelevant), syn hydroxylation transforms cis alkenes into erythro (or meso) diols and trans alkenes into threo (or dl) diols. anti Hydroxylation of cis alkenes gives threo (or dl) diols, whereas anti hydroxylation of trans alkenes yields erythro (or meso) diols. syn Hydroxylation of cycloalkenes gives cis diols, whereas anti hydroxylation furnishes trans diols (Table I). 

Zirconium-catalyzed carbomagnesiation of enJo-5-norbonen-2-ol affords the corresponding product in 97% yield and >99 1 regioselecfivity [94] (Scheme 7-83). Since C—C bond formation occurs from the exo face, it follows that the alkyl adduct may arise from an anti mode of addition [94]. 

Only products which can be attributed to bromohydrin (salt) intermediates are formed when epoxides are treated with LiBr (solubilizer) in refluxing benzene. Any apparent exceptions to this generalization are believed to be due to interconversion of halohydrin stereoisomers, as discussed below. The bromohydrin is formed by traditional anti opening (antiperiplanar, probably nearly exclusively trans diaxial). It has been established that a model epoxide (1-methylcyclohexene oxide) reacts by a process that is kinetically first order in a 1 1 complex of LiBr-HMPA, but the state of aggregation [n in the formula (LiBr HMPA)n] is not known.The nature of the epoxide-(LiBr-HMPA)n interaction that allows bromide to attack (exclusively) in the anti mode is not known, but must require fairly extensive ion pair (aggregate) reorganization. 

Figure 43-12 Histogram of NAT2 phenotypical activities as obtained by the caffeine test 5 hr urine collection obtained after administration of caffeine, and analyzed for caffeine metabolite concentrations.Values represent the logarithmically transformed ratio of metabolites 5-acetylamino-6-formylamino-3-methy -uracil (AFMU) and I-methyixanthine (IX). From the distinct biomodal distribution an anti mode of log(0.50)...

The LAM modes involve deformation of the in-plane C-C-C angles of the alkane. There are only n-2 such angles and so, in Eq. (10.2) mode = n-2. To assign the LAMs a twofold approach was adopted. The -alkanes have either C v ( = odd) or (n = even) symmetry. The LAMs belong to the Ai 01 B representations ( = odd) or Ag or representations (n = even). For the first mode, LAM-1 (v = 1) with ki = 7t/( -1), the eigenvectors exhibit a node at the chain centre with + and anti-mode, one at each end of the chain, LAM-1 must be totally symmetric. LAM-2 has two nodes and so must be antisymmetric, LAM-3 must be totally symmetric again since it has three nodes and so on. Thus the modes must follow the sequence ... 

The earliest studies relative to the mechanism was the stereochemical work of Conforth, Popjak, and their collaborators [49]. They concluded that there was an inversion of configuration at C-1 of the allylic substrate, consistent with a concerted process, the new carbon-to-carbon bond being formed as the carbon-to-oxygen bond is cleaved. They also felt that elimination of a proton from C-2 of the isopentenyl moiety would not be concerted with this, since suprafacial (same side) reactions are generally considered unfavorable. To circumvent this, a 2-stage mechanism involving an electron donor X , with X being covalently linked to the initial condensation product, was proposed. The X residue is then lost simultaneously with elimination of the proton in an anti-mode (Fig. 12). 

BF3 -Et20 has been employed to activate vinyl oxazolidinones towards Sn2 reactions with organocuprates. These reactions proceed primarily via an anti mode of addition, providing dipeptide isosteres in good yield. Similar results were obtained using allylic mesylates, although in this case access to both the cis and trans product was possible by appropriate choice of solvent (Et20 = trans THF = cis). ... 

Addition of Pd-N species can be envisioned (proceeding probably in an anti mode, with prior coordination of the olefin by Pd), but surprisingly this strategy has not been pursued extensively. 

Various Ca(II) complexes with carboxylates have been synthesized and crys-tallographically characterized [75]. Three modes are most commonly observed for these complexes the unidentate mode, the bidentate mode, and the anti-mode. In the unidentate mode, the Ca ion interacts with only one of the two 0 atoms of the carboxylate group. The coordinating atom is a carboxylate oxyanion rather than the carbonyl 0 atom. In the bidentate mode, the two 0 atoms of the carboxylate chelates to one Ca ion. In the anti-mode, the Ca complex is chelated between one of the carboxylate 0 atoms and a neighboring atom. Furthermore, the anti-mode is involved in a polynuclear mode with the 0 atom of the carboxylate forming a bridge between two Ca ions. 

Dehydrobromination of 2,3-dibromobutane proceeds by anti mode over Na-, K-and Cs-exchanged silica gels, while silica gel and its Li-exchanged form is inactive for the reaction. ... 

Another stereochemical characteristic of these cyclizations is the equatorial disposition of both the entering electrophile and nucleophile, as expected for overall anti addition to both double bonds (727—123). The anti mode of addition appears to be followed in the initial electrophilic attack in all cases. However, the stereoselectivity in the approach of the nucleophile is evidently less since minor amounts of axial acetates are formed in the additions to the above model cyclodecadienes (73) and (74) (722). 

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