Enantiopure bis

As reported by Steel et al. three structural isomers of bis(camphor-pyrazol-l-yl)methane (21a, 21b and 21c) are formed by coupling of camphorpyrazole 10 [i.e., (4S,7i )-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methano-l(2)H-indazole] with CH2CI2 (121). Isomer 21c can be separated from the other two structural isomers by crystallization or column chomatography. Deprotonation at the bridging carbon atom, subsequent reaction with carbon dioxide and acidic workup yields the enantiopure bis(camphorpyrazol-l-yl)acetic acid Hbpa (8) (Scheme 17, Fig. 19) (116). Due to missing substituents at the p5rrazolyl carbon C5 and a hence likely ortho metallation, isomers 21a and 21b are not suited for his reaction (72). 

The ionic liquid [bmim][BF ] is known to catalyze the aza-Diels-Alder reaction in the synthesis of pyrano- and furanoquinolines [190]. This reaction was also catalyzed by the enantiopure bis-imidazolinium salt 67 in 67% yield with an endo. exo ratio of 60 40 (Scheme 69) [191]. The product was obtained as a race-mate. In addition the aza-Diels-Alder reaction with imines and Danishefsky s diene was catalyzed by the salt 67 giving racemic product. The salt and its analogues could be easily prepared via the oxidation of the corresponding aminals [192]. Investigation of the influence of the counter anion in achiral C2-substituted imidazolinium salts, which can be also described as 4,5-dihydroimidazolium or saturated imidazolium salts, in the aza-Diels-Alder reaction showed, that the catalytic activity increased, the more lipophilic the counter anion and therefore the more hydrophobic the salt was [193]. 

It was also found that the Padua reagent was useful for the oxidation of three isomeric bis(methylsulfmyl)benzenes with r-BuOOH, yielding the corresponding almost enantiopure bis-sulfoxides [64]. As mentioned above, the enantioselectivity of the first oxidation was enhanced (Horeau principle), because a minor amount of meso-disulfoxide was formed and separated from the chiral disulfoxide. It was reported that the Orsay reagent with cumyl hydroperoxide oxidized an /V-protected 2-.S -methylindole with moderate enantioselectivity, whereas the Padua protocol afforded the desired sulfoxide with 80% ee [65],... 

Enantiopure bis-P-amino acids can be prepared from chiral bis-sulfinimines.37 Bis-sulfinimine (Ss,Ss)-160 and the sodium enolate of methyl acetate react to give 161 as a diastereomeric mixture. The major isomer (5s,/ ,Ss,/ )-161 can be isolated by preparative reverse-phase HPLC in 46% yield. Hydrolysis of (Ss,/ ,Ss,/ )-161 gave bis-P-amino ester (/ ,/ )-162 in >97% ee and 86% yield.37... 

The enantioselective total synthesis of the annonacenous acetogenin (+)-parviflorin was accomplished by T.R. Hoye and co-workers." The b/s-tetrahydrofuran backbone of the natural product was constructed using a sequential double Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylation. The bis allylic alcohol was epoxidized using L-(+)-DET to give the essentially enantiopure bis epoxide in 87% yield. 

Allyltrimethylsilanes react with triplet excited 2,3-dicyano-5,6-dimethylpyra-zine to give diazatricyclooctenes (115), possibly via intermediate (114) formed from ring-opening of an initially-formed [2+2]adduct. Intramolecular [2+2]-cycloaddition yields the pentacyclic compound (116) on irradiation of the corresponding tethered enantiopure bis-2,3-dihydro-4-pyridone. Addition of ethylene to the corresponding a,P-unsaturated-y-lactams in acetone yields (117) and (118) as the major photoproducts. ... 

M,M-dibenzylamino)-3-phenylpropanal, TMEDA or the enantiopure bis(oxa-zoline), confirmed a dynamic kinetic resolution pathway for this reaction. Ab initio calculations showed that the C-Li bond prefers the conformation antiperi-planar to the S-Cjpj bond [42] due to the n-o negative hyperconjugation of a-lithiated benzyl phenyl sulfide, as described in Sect. 1.3 (Fig. 13). Thus, this enantioselective reaction was assumed to proceed through a four-membered cyclic transition state stabilized by the negative hyperconjugation. 

Ferrocenylimines derived from benzoylferrocene were synthesized and cyclopalladated by Bosque et The cr(GH) bonds in ferrocenyl- and bis(ferrocenyl)imines were activated in cyclopalladation reactions. Depending on the imine, five- and six-membered palladacycles were obtained. Bosque and Lopez also studied the cyclopalladation of mono- and bidentate primary ferrocenylimines. Mak / /. studied the cyclopalladation of ferrocenylimines in which the nitrogen of the imine is also substituted with a cyclic ether. Enantiopure bis(//-acetato)-bridged dimers were obtained. The insertion of diphenylacetylene was also investigated. 

A AgNOs-mediated skeletal rearrangement of a bromolac-tone precursor is the key step for the synthesis of enantiopure bis(phosphinomethyl) norbornane ligands (eq 11). ... 

The disclosure, in 1982, that cationic, enantiopure BINAP-Rh(i) complexes can induce highly enantioselective isomerizations of allylic amines in THF or acetone, at or below room temperature, to afford optically active enamines in >95 % yield and >95 % ee, thus constituted a major breakthrough.67-68 This important discovery emerged from an impressive collaborative effort between chemists representing Osaka University, the Takasago Corporation, the Institute for Molecular Science at Okazaki, Japan, and Nagoya University. BINAP, 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (Scheme 7), is a fully arylated, chiral diphosphine which was introduced in... 

Jacobsen demonstrated that the (salen)Cr system used to effect intermolecular, cooperative asymmetric azidolysis of meso-epoxides (Schemes 7.3 and 7.5) could be applied to sulfur-centered nucleophiles (Scheme 7.13). In order to overcome moderate enantioselectivity (<60% ee), a dithiol nucleophile was employed as part of a double resolution strategy in which the minor enantiomer of the monoaddition product reacts preferentially to form the meso- bis-addition product, thereby increasing the ee of the C2-symmetric bis-addition product. Enantiopure 1,2-mer-capto alcohols (>99% ee) were obtained from the meso-epoxide in ca. 50% overall yield by a burdensome (though effective) multistep sequence, [23]. 

RRM of enantiopure cyclopentene 382, induced by commercially available catalyst C, was the key step in Blechert s total synthesis of the bis-piperidine alkaloid (+)-astrophylline (384) [159]. Exposure of metathesis precursor 382 to only 1 mol% C provided within 2 h bicycle 383 in 82% yield (Scheme 75). 

An other type of bis-imidazoliums salts 22, resulting of a base-induced 1,3-cycloaddition of tosyl-methylisocyanide (TosMlC) to the enantiopure diimine 23, was obtained by Douthwaite according to Scheme 14 [23]. 

In 2004, ruthenium-catalysed asymmetric cyclopropanations of styrene derivatives with diazoesters were also performed by Masson et al., using chiral 2,6-bis(thiazolines)pyridines. These ligands were prepared from dithioesters and commercially available enantiopure 2-aminoalcohols. When the cyclopropanation of styrene with diazoethylacetate was performed with these ligands in the presence of ruthenium, enantioselectivities of up to 85% ee were obtained (Scheme 6.6). The scope of this methodology was extended to various styrene derivatives and to isopropyl diazomethylphosphonate with good yields and enantioselectivities. The comparative evaluation of enantiocontrol for cyclopropanation of styrene with chiral ruthenium-bis(oxazolines), Ru-Pybox, and chiral ruthenium-bis(thiazolines), Ru-thia-Pybox, have shown many similarities with, in some cases, good enantiomeric excesses. The modification... 

Several alkylboranes are available in enantiomerically enriched or pure form and can be used to prepare enantiomerically enriched alcohols and other compounds available via organoborane intermediates.196 One route to enantiopure boranes is by hydroboration of readily available terpenes that occur naturally in enantiomerically enriched or pure form. The most thoroughly investigated of these is bis-(isopinocampheyl)borane (Ipc)2BH), which can be prepared in 100% enantiomeric purity from the readily available terpene a-pinene.197 Both enantiomers are available. 

Having demonstrated a practical and reliable method to access 2-arylpyrrolidines in high enantioselectivity, we felt that a noteworthy extension of this methodology would lie in its application to bis-arylated products 27, providing a rapid and efficient approach to enantiopure C2-symmetric 2,5-diarylpyrrolidines, which have been identified as valuable chiral auxiliaries and chiral ligand manifolds [29]. Towards this end, substrate 26a was subjected to the standard arylation conditions, which produced 2,5-diphenyl-N-Boc-pyrrolidine 27 in a 96 4 diastereomeric ratio, and 57% isolated yield (s-BuIi/TMEDA produced 27 in lower d.r. (66 34) and yield (42%)), as depicted in Scheme 8.13. 

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