Anti-stereochemistry

Photodimers of IV-methylisoindole and isobenzofuran have been isolated [8+8] dimers are the major products. The [8 + 8] dimer (30) obtained by UV irradiation of an acetone solution of isobenzofuran at -60 °C has anti stereochemistry (78HCA444, 82CC1195). 

Entries 1 and 2 in Scheme 2.9 are typical of concerted syn addition to alkene double bonds. On treatment with peroxyacetic acid, the Z-alkene affords the cis-oxirane, whereas the -alkene affords only the iraws-oxirane. Similarly, addition of dibromocarbene to Z-2-butene yields exclusively l,l-dibromo-cw-2,3-dimethylcyclopropane, whereas only 1,1-dibromo-/ra 5-2,3-dimethylcyclopropane is formed from -2-butene. There are also numerous stereospecific anti additions. Entiy 3 shows the anti stereochemistry typical of bromination of simple alkenes. 

Anti stereochemistry can be explained by a mechanism in which the alkene interacts simultaneously with the proton-donating hydrogen halide and with a source of halide ion, either a second molecule of hydrogen halide or a free halide ion. The anti stereochemistry is consistent with the expectation that the attack of halide ion would be from the opposite... 

If the addition of Br to the alkene results in a bromonium ion, the anti stereochemistry can be readily eiqilained. Nucleophilic ring opening by bromide ion would occur by backside attack at carbon, with rupture of one of the C—Br bonds, giving overall anti addition. 

Addition of hydrogen halides to alkenes is not stereospecific. In contrast, addition of Br2 proceeds exclusively with anti stereochemistry. 

When the halogenation reaction is carried out on a cycloalkene, such as cyclopentene, only the trews stereoisomer of the dihalide addition product is formed rather than the mixture of cis and trans isomers that might have been expected if a planar carbocation intermediate were involved. We say that the reaction occurs with anti stereochemistry, meaning that the two bromine atoms come from opposite faces of the double bond—one from the top face and one from the bottom face. 

An explanation for the observed anti stereochemistry of addition was suggested in 1937 by George Kimball and Irving Roberts, who proposed that the... 

How does the formation of a bromonium ion account for the observed anti stereochemistry of addition to cyclopentene If a bromonium ion is formed as an intermediate, we can imagine that the large bromine atom might "shield" one side of the molecule. Reaction with Br ion in the second step could then occur only from the opposite, unshielded side to give trans product. 

HC1, HBr, and HI add to alkenes by a two-step electrophilic addition mechanism. Initial reaction of the nucleophilic double bond with H+ gives a carbo-cation intermediate, which then reacts with halide ion. Bromine and chlorine add to alkenes via three-membered-ring bromonium ion or chloronium ion intermediates to give addition products having anti stereochemistry. If water is present during the halogen addition reaction, a halohydrin is formed. 

Problem 9.26 The aconitase-catalyzed addition of water to ds-aconitate in the citric acid cycle occurs with the following stereochemistry. Does the addition of the OH group occur on the Re or the Si face of the substrate What about the addition of the H Does the reaction have syn or anti stereochemistry ... 

Diols can be prepared either by direct hydroxylation of an alkene with 0s04 followed by reduction with NaHSOj or by acid-catalyzed hydrolysis of an epoxide (Section 7.8). The 0s04 reaction occurs with syn stereochemistry to give a cis diol, and epoxide opening occurs with anti stereochemistry to give a trans diol. 

Anti stereochemistry (Section 7.2) The opposite of syn. An anti addition reaction is one in which the two ends of the double bond are attacked from different sides. An anti elimination reaction is one in which the two groups leave from opposite sides of the molecule. 

Addition of ( )-enolates to ( )-l-nitropropene favors products with the syn stereochemistry while products with the anti stereochemistry are favored from the reaction of ( )-enolates with (Z)-1 -nitropropene. 

Reaction of the anion derived from the tosyl imide of l,3,S-trithiane with alkyl iodides gives a mixture of the mono- and di- alkylated products, in which anti stereochemistry predominates. The analogous 1,3-dithiane derivative is only monoalkylated <96JCS(P1)313>. 

In 2008, Grisi et al. reported three ruthenium complexes 65-67 bearing chiral, symmetrical monodentate NHC ligands with two iV-(S)-phenylethyl side chains [74] (Fig. 3.26). Three different types of backbones were incorporated into the AT-heterocyclic moiety of the ligands. When achiral triene 57 was treated with catalysts 65-67 under identical reaction conditions, a dramatic difference was observed. As expected, the absence of backbone chirality in complex 65 makes it completely inefficient for inducing enantioselectivity in the formation of 58. Similarly, the mismatched chiral backbone framework of complex 66 was not able to promote asymmetric RCM of 57. In contrast, appreciable albeit low selectivity (33% ee) was observed when the backbone possessed anti stereochemistry. 

Scheme 2.6 shows some examples of the use of chiral auxiliaries in the aldol and Mukaiyama reactions. The reaction in Entry 1 involves an achiral aldehyde and the chiral auxiliary is the only influence on the reaction diastereoselectivity, which is very high. The Z-boron enolate results in syn diastereoselectivity. Entry 2 has both an a-methyl and a (3-benzyloxy substituent in the aldehyde reactant. The 2,3-syn relationship arises from the Z-configuration of the enolate, and the 3,4-anti stereochemistry is determined by the stereocenters in the aldehyde. The product was isolated as an ester after methanolysis. Entry 3, which is very similar to Entry 2, was done on a 60-kg scale in a process development investigation for the potential antitumor agent (+)-discodermolide (see page 1244). 

Part B of Scheme 4.5 gives some examples of cyclizations induced by selenium electrophiles. Entries 9 to 13 are various selenyletherifications. All exhibit anti stereochemistry. Entries 14 and 15 are selenyllactonizations. Entries 17 and 18 involve amido groups as the internal nucleophile. Entry 17 is an 5-exo cyclization in which the amido oxygen is the more reactive nucleophilic site, leading to an iminolactone. Geometric factors favor N-cyclization in the latter case. 

The configuration at the newly formed C-C bond is then controlled by the stereochemistry of the double bond in the allylic alcohol. The. E-isomer gives a syn orientation, whereas the Z-isomer gives rise to anti stereochemistry.247... 

Reactions of this type lead to preferential formation of the anti stereochemistry at the new C-C bond. 

The cyclic mechanism predicts that the addition reaction will be stereospecific with respect to the geometry of the double bond in the allylic group, and this has been demonstrated to be the case. The E- and Z-2-butenyl cyclic boronates 1 and 2 were synthesized and allowed to react with aldehydes. The F-boronate gave the carbinol with anti stereochemistry, whereas the Z-boronate resulted in the syn product.37... 

This methodology was applied to construct the all anti stereochemistry for a segment of the antibiotic zincophorin. 

The anti stereochemistry is consistent with a cyclic TS, but the reaction is stereocon-vergent for the E- and Z-2-butenylstannanes, indicating that isomerization must occur at the transmetallation stage. The adducts are equilibrated at 82 °C and under these conditions the anti product is isolated on workup. 

Scheme 12.15 gives some examples of both acid-catalyzed and nucleophilic ring openings of epoxides. Entries 1 and 2 are cases in which epoxidation and solvolysis are carried out without isolation of the epoxide. Both cases also illustrate the preference for anti stereochemistry. The regioselectivity in Entry 3 is indicative of dominant bond cleavage in the TS. The reaction in Entry 4 was studied in a number of solvents. The product results from net syn addition as a result of phenonium ion participation. The ds-epoxide also gives mainly the syn product, presumably via isomerization to the... 

In 1984, Corey and Boaz rationalized the anti stereochemistry observed in most of the organocopper-mediated SN2 displacements [4]. The stereoelectronic effect arising from a bidentate binding involves a d-orbital of a nucleophilic copper and... 

Liebeskind favors a mechanism for the formation of 114 that cites the i72-alkene complex 115 as a crucial intermediate. The cobalt moiety coordinates on the opposite face to the R1 substituent, which means that upon disrotatory opening98 of the carbocycle the R1 group rotates inwards, accounting for the favored anti stereochemistry. The possibility of the vinylke-... 

Transmetalations with first row transition metal elements such as titanium or manganese have produced useful synthetic applications. Organotitanate species of type 123 show the advantage of high Sn2 selectivity in the anti stereochemistry of the resulting copper(I) intermediates (Scheme 2.56) [119, 120],... 

Cuprates react rapidly with allylic halides (or acetates) [17, 23], propargyl halides (or acetates) [106-108], and vinyloxiranes, often with 5 2 regioselectivity (Scheme 10.9) [17]. The reaction takes place with anti stereochemistry (with respect to the leaving group), while syn substitution occurs when an allylic carbamate is employed as the substrate [109]. 

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