Atropisomers stereoselective

In the syntheses of these compounds, very high stereoselectivity was noted. In every case, the entering dienophile approaches the least hindered side of the substituted anthracene. Thus tire ap isomer is the almost exclusive product of the reaction. As an extension of this finding, atropisomers of 9-(l,I-dimethyl-2-phenylethyl)-2,3-dichlorotriptycene (101) were prepared separately the ap form by treating 9-( 1,1 -dimethyl-2-phenylethyl)anthracene with 4,5-dichlorobenzyne, and the sc form by treating 2,3-dichloro-9-(l,l-dimethyl-2-phenylethyl)-... 

Preference will be given to those methods that have proven to be applicable to the stereoselective total synthesis of demanding target molecules, such as naturally occurring biaryls. Of special interest are those methods that allow the optional synthesis of either of the two atropisomers in question. 

Using a different dimerization method, namely phenolic oxidation, chiral substrates react in a more stereoselective manner than under reductive conditions. The choice of oxidizing reagent may drastically affect the stereochemical outcome of the reaction. Thus, when potassium hexacyanoferrate(III) is used (17 )-l,2,3,4-tetrahydro-6-methoxy-l,2-dimethyl-7-isoquino-linol couples to give a mixture of atropisomers 3 in 38 % yield and with a d.r. (M)I(P) of 45 553,4. Only one single atropisomer, namely (A/)-3, is formed, in a 66% yield by anodic oxidation, which is attributed to electrode surface effects3. 

Most benzylic organolithiums, unless they bear an a heteroatom, are configurationally unstable over a period of seconds or more (see section 5.1.11), so any stereoselectivity in lateral lithiation is rarely detectable. However, as implied above, the lateral lithiation of tertiary 1-naphthamides 344 is stereoselective, and yields a single diastereoisomeric atropisomer of the organolithium 346b.159-139-140 Both diastereoisomers of 346 were characterised by NMR. These organolithiums react with most electrophiles to give 372 with retention of stereochemistry, but with trialkyltin halides with inversion (see section 6.1.4). 

The potassium enolate generated from 23 is regarded as an enantiomeric atropisomer. Recently non-biaryl atropisomers have been receiving more attention in asymmetric synthesis.19 Most of them employ atropisomers that are configurationally stable at room temperature, while attention in this chapter is focused on asymmetric reactions that proceed via chiral nonracemic enolate intermediates that can exist only in a limited time. An application of configurationally stable atropisomeric amide to a chiral auxiliary for stereoselective alkylation has been reported by Simpkins and co-workers (Scheme 3.10).20... 

Reactions like these, in which stereoselectivity is the consequence of steric hindrance to bond rotation, are most well known among the biaryls, and derivatives of binaphthyl have provided chemists with a valuable range of chiral ligands [4-6]. But the biaryls are only a small subset of axially chiral compounds containing two trigonal centres linked by a rotationally restricted single bond. Many others are known, some with much greater barriers to rotation than Fuji s enol ether [7]. Yet until quite recently there were no reports of reactions in which nonbiaryl atropisomers were the source, conveyor, or product of asymmetric induction. 

The ether derivatives 0,0,0-trimethylkorupensamine A (248) and B have both been synthesised by a route which commenced with a lengthy sequence to the biaryl 249 from 3,5-dimethylanisole (ref. 95) (Scheme 32). Reduction of 249 with LiAlHa and oxidation gave aldehyde 250 which upon Wadsworth-Emmons-Homer extension, reduction and Sharpless asymmetric epoxidation provided epoxide 251 and the corresponding atropisomer in almost equal amounts which were separated by silica gel chromatography. The derived alcohol 252, obtained by mesylation of 251 and in situ reduction, was then converted into the acetamide 253 by displacement with azide under Mitsunobu conditions followed by reduction and acetylation. Ring closure followed by stereoselective reduction then yielded 0,0,0-trimethylkorupensamine A (248). The synthesis of 0,0,0-triraethylkorupensamine B was accomplished in a similar manner using the atropisomer of 251 obtained in the epoxidation step. 

Asymmetric induction (See also Enantioselective) chiral ketones, 62, 106-107 chiral sulfoxides, 8-9 steroid synthesis, 27, 278-281 Asymmetric syntheses. See Enantioselective. .. Asymmetry of vesicle membranes, 351 dATP. See 2 -Deoxynucleoside 5 -triphosphates Atropisomers binap chelands, 102-103 Kemp s acid arylimides, 347 porphyrin oligomers, 348—349 5,10,15,20-tetraarylporphyrins, 253 Axial/equatorial stereoselectivity ... 

Conformational isomers that are stable, isolable compounds are called atropisomets. The existence of chiral atropisomers has been exploited to great effect in the development of chiral catalysts for stereoselective reactions. An example is BINAP, shown below in its enantiomeric forms ... 

Planar chiral cyclopentadienyhnetal complexes (M=Zr, Ti, Co, Fe, Mo) are stereoselective catalysts, which have received attention in a number of as3munetric synthetic applications [42]. The conpling of l-(p-tolyl-snlfinyl)naphthalene-2-carboxylate ester 50 with indenyl lithium 51 and fluorenyl Uthinm 52 provides access to l-(2 -methyl-3 -indenyl)naphthalene (53) and 9-(l -naphthyl)fluorene (54), respectively, as single rotamers (Scheme 8.12) [43-45]. The atropisomer-ism arises fiom hindered rotation abont the bond between the cyclopentadienyl ring and the naphthalene moiety. Ligands 53 and 54 are building blocks for the enantiospecific synthesis of planar chiral bidentate ansa zirconocene complexes 55 and 56 [46,47]. 

Benzylic organolithium compounds are in general configurationally unstable. However, the lateral lithiation of tertiary 2-alkyl-l-naphthamides, such as 170, was stereoselective and yielded a single diastereomeric atropisomer 171 [143], which reacted with several electrophiles with retention, to give compounds 172 [144], except with trialkyltin halides for which an inversion of the configuration was observed (Scheme 2.23) [144a[. 

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