Anti isomer

The addition of methylmagnesium iodide to 2-phenylpropanal is stereoselective in producing twice as much syn-3-phenyl-2-butanol as the anti isomer (entry 5). The stereoselective formation of a particular configuration at a new stereogenic center in a reaction of a chiral reactant is called asymmetric induction. This particular case is one in which the stereochemistry can be predicted on the basis of an empirical correlation called Cram s rule. The structural and mechanistic basis of Cramls rule will be discussed in Chapter 3. 

In contiaat, die isomer, in which tire double bond is not in a position to participate in die iooizsdon step, reacts 10 times slower than die anti isomer. The reaction product is derived fiom a rearranged caibocation ion that is stabilized by virtue of being allylic. ... 

In the discussion of the syn- and anft-norbomenyl tosylates (p. 312), it was pointed out that, relative to 7-norbomyl tosylate, the reactivities of the syn and anti isomers were 10 and 10, respectively. The high reactivity of the anti isomer was attributed to participation of die carbon-carbon double bond. What is the source of the 10 factor of acceleration in the syn isomer relative to the saturated model ... 

In aqueous dioxane, the endo-anti isomer gave a product mixture consistent of alcohol N and the corresponding ester (derived from capture of the leaving group p-nitrobenzoate). The other isomers gave much more complex product mixtures which were not completely characterized. Explain the trend in rates and discuss the structural reason for the stereochemical course of the reaction in the case of the endo-anti isomer. 

The syn isomer can achieve a conjugated system with angles of up to 35° between adjacent p orbitals. The anti isomer is much more twisted. An X-ray crystal structure of the syn isomer shows C—C bond lengths between 1.368 and 1.418 A for the conjugated system (Fig. 9.3). ° The spectroscopic properties of the syn isomer are consistent with considering it to be a delocalized annulene. B3LYP calculations indicate that both the syn and anti structures are stabilized by delocalization, the syn (17.6kcal/mol) more so than the anti (8.1 kcal). ... 

The NMR spectrum of the syn isomer shows evidence of a diamagnetic ring current, based on both the relatively low-field position of the vinylic hydrogens and the upfield shift of the methylene hydrogens. The anti isomer shows much less pronounced shifts. The X-ray crystal structure of the syn isomer shows a moderate level of bond alternation, ranging ftom 1.36 to 1.45 A (Fig. 9.4A). In the anti isomer, bond alternation is more pronounced, vith the double bond in the center ring being essentially a localized double bond (Fig. 9.4B). 

Recently, the structure of the bis-imidazo fused 1,4,5,8-tetraazafulvalene 141a (anti-isomer) was reported (97LAR617). Tire ideal planarity of the tetraazafulvalene framework is striking the exocyclic aryl residues are slightly bent out of the plane. As expected, the central C—C distance... 

Pd(0)-catalyzed hydrogenolysis of vinylepoxides offers an attractive regio- and dia-stereoselective route to homoallylic alcohols (Scheme 9.36) [104, 155, 156]. Thus, hydrogenolysis of ( ) olefin 88 affords syn isomer 89 with inversion of configuration at the allylic carbon, while subjection of (Z) isomer 90 to identical reaction conditions results in the anti isomer 91. The outcomes of these reactions are ex-... 

Tin(Il) shows considerable affinity towards nitrogen, therefore is expected to activate the imino group. The diastereoselective addition of tin(II) enolates derived from thioesters 1 to x-imino-esters 2 is reported12. This reaction proceeds smoothly to afford. vi w-/j-amino acid derivatives 3 (d.r. 95 5) in good yields. Lithium, magnesium, and zinc enolates do not react while titanium enolates give the adducts in low yield with preferential formation of the anti-isomer. 

The addition of the lithium azaenolate of the SAMP hydrazone of propanal to methyl (E)-2-butenoate to furnish the (S,S,S)-adduct in 58% yield with > 96% ee and de is illustrative for the efficiency of this asymmetric Michael addition10°. Only the anti-isomer (an / adduct) is found. This methodology was used in the synthesis of pheromones of the small forest and red wood ant200. 

Thus, the observed stereoselectivity means the exclusive formation of the anti-isomer (a). This conclusion was confirmed by NMR analysis63 (see Section III.B.4.b) and, clearly, can be extended and generalized with respect to larger cyclic sulfoxide systems. 

Rotational equilibria of 2-carbonyl substituted thiophene and furan derivatives were calculated and show that the 2-substituent favors the anti-isomer in thiophene <96MI199>. NMR shifts of 35 alkyl 3-hydroxythiophene-2-carboxylates and 3-alkylamino-l-(3-thienyloxy)-2-propanols have been compiled and analyzed <96HC17>. 

The checkers obtained 12.8-13.0 g. (52-53%), m.p. 84-86°, in the first crop and 2.7-3.4 g. (11-14%), m.p. 52-62°, in the second crop. Recrystallization of the former from methanol gave 11.5 g. of crystals, m.p. 84-86°, suggesting that the first crop is a pure single isomer. A proton magnetic resonance spectrum in chloroform-d of the second crop shows two singlets at 8 1.62 and 1.64 for the terf-butyl groups. Thus this material is a mixture of syn and anti isomers. Both the first and second crops proved equally useful for tcrf-butoxycarbonylation of an amino acid. 

In 1980 and 1982, Callot and co-workers reported that Rh(Por)l catalyzed the reaction between alkenes and ethyl diazoacetate to give syn cyclopropoanes as the major products (Eq. 25). " This was unusual as most transition metal catalysts for this reaction give the anti isomers as the predominant products. Kodadek and co-workers followed up this early report and put considerable effort into trying to improve the syn/anti ratios and enantioselectivity using porphyrins with chiral substituents. 

It is clear from the foregoing that ring closure to five-membered rings fused to the isoxazolidine, regardless whether part of a pyrrolizidine or of an indolizidine system, led mainly to the cis-anti isomers (see 243 a, b and 246 a, b)... 

The facile arylation of aldehydes with arylboronic acid has prompted the exploration of asymmetric versions of this reaction. However, this field has been scarcely explored and only few examples have been reported in the literature, with moderate results. The first diastereoselective example was described by Ftirstner and coworkers. By reacting the Gamer aldehyde 15 with phenylboronic acid under their set of experimental conditions (i.e. RhClj-SH O, IPr HCl) (Scheme 7.4) [21], the secondary alcohol was obtained in higher selectivity than that observed in the addition of phenylmagnesium bromide reported by Joullie (de = 94% versus 66%), with the anti isomer as the major compound [29]. 

The enolates derived from cyclic ketones are necessarily /(-isomers. The enolate of cyclohexanone reacts with benzaldehyde to give both possible stereoisomeric products. The stereoselectivity is about 5 1 in favor of the anti isomer under optimum... 

Mixed aldehyde-aldehyde additions have been carried out using TiCl4 and TMEDA. The reaction gives syn adducts, presumably through a cyclic TS. Treatment of the syn adducts with 1 mol % Ti(0-i-Pr)4 leads to equilibration to the more stable anti isomer.23... 

Entries 4 and 9 are closely related structures that illustrate the ability to control stereochemistry by choice of the Lewis acid. In Entry 4, the Lewis acid is BF3 and the (3-oxygen is protected as a f-butyldiphenylsilyl derivative. This leads to reaction through an open TS, and the reaction is under steric control, resulting in the 3,4-syn product. In Entry 9, the enolate is formed using di-n-butylboron triflate (1.2 equiv.), which permits the aldehyde to form a chelate. The chelated aldehyde then reacts via an open TS with respect to the silyl ketene acetal, and the 3,4-anti isomer dominates by more than 20 1. 

A 3 -benzyloxy ketone gives preferential 2,2 -syn stereochemistry through a chelated TS for several titanium enolates. The best results were obtained using isopropoxytitanium trichloride.112 The corresponding /(-boron enolate gives the 2,2 -anti-2,3-anti isomer as the main product through a nonchelated TS.110... 

As already discussed for aldol and Robinson annulation reactions, proline is also a catalyst for enantioselective Mannich reactions. Proline effectively catalyzes the reactions of aldehydes such as 3-methylbutanal and hexanal with /V-arylimines of ethyl glyoxalate.196 These reactions show 2,3-syn selectivity, although the products with small alkyl groups tend to isomerize to the anti isomer. 

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