Ci selectivity

The diacetoxylation of E,E)- and ( ,Z)-2.4-hexadiene (351 and 353) is stereospecific, and 2,5-dimethylfurans (352 and 354) of different stereochemistry have been prepared from the isomers. Two different carboxylates are introduced with high cis selectivity by the reaction of 1,3-cyclohexadiene and... 

Stereoselective and chemoselective semihydrogenation of the internal alkyne 208 to the ew-alkene 210 is achieved by the Pd-catalyzed reaction of some hydride sources. Tetramethyldihydrosiloxane (TMDHS) (209) i.s used in the presence of AcOH[116]. (EtO)3SiH in aqueous THF is also effective for the reduction of alkynes to di-alkenes[l 17], Semihydrogenation to the d.v-alkene 211 is possible also with triethylammonium formate with Pd on carbon[118]. Good yields and high cis selectivity are obtained by catalysis with Pd2fdba)3-Bu3P[119],... 

Tliis nietliod can be extended to die preparation of alkenylcoppet conipounds. Tlius, treatment of die iodoalkenyl azide 10 widi iiBuLi at -100 C iSdienie 2.3), followed by transnietaladon witli Znl2 in THF and tlien by a second Iransnieta-lalion widi CuCN-2LiCl, produces die copper species 11. Tliis tlien effects a cis-selective carboctipralion of etliyl propiolate lo ftitnisb tlie f , ) diene 12 in 81%... 

The BF3 Et20-catalyzed aziridination of compounds 47 (Scheme 3.15) with a diazo ester derived from (R)-pantolacetone gave aziridine-2-carboxylates 48 [59]. The reaction exhibited both high cis selectivity (>95 <5) and excellent diastereose-lectivity. Treatment of a-amino nitrile 49 (Scheme 3.16) with ethyl diazoacetate in the presence of 0.5 equivalent of SnCl4 afforded aziridines 50 and 51 in 39% yield in a ratio of 75 25 [60]. 

Remarkably high cis selectivities are observed in case of an oxygen substituent at C-4... 

The reaction of alkenylcarbene complexes and imines in the presence of a Lewis acid generates pyrroline derivatives as a result of a [3C+2S] cyclisation process [76]. This reaction has been extended to an asymmetric version by the use of chiral alkenylcarbene complexes derived from several chiral alcohols. However, the best results are found when (-)-8-phenylmenthol-derived complexes are used and catalytic amounts of Sn(OTf)2 are added to the reaction. In these conditions high levels of trans/cis selectivity are achieved and the hydrolysis of the major tram diastereoisomers allows the preparation of optically pure 2,5-disubstituted-3-pyrrolidinone derivatives (Scheme 29). 

The acyl selenide 19 affords the decarbonylated )S-lactam in good yield. A N-hydroxypyridine-2-thione ester 20 is used in the key step to construct the chiral cis-cyclopropane structure in compounds designed as antidopaminergic agents. The observed high cis selectivity is due to the hydrogen abstraction from the sterically demanding (TMSlsSiH, which occurs from the less-hindered side of the intermediate cyclopropyl radical. 

It is concluded from these results that with this kind of non-C2 symmetric ligand (that led necessarily to poor enantioselectivities in homogeneous phase), it is possible to exploit support effects to change the trans/cis selectivity and to improve the enantioselectivity. This is demonstrated for the trans-cyclopropanes obtained with ligand 10a in styrene. Due to the relative disposition of the ester and phenyl groups in the transition state, support ef-... 

Changing catalyst support from carbon to calcium carbonate leads to dramatic improvement of the cis/tran ratio from 6 1 to 18 1, that is the cis selectivity increases from 85.7% to 94.7%. The reason for better selectivity on CaC03 supported catalyst is attributed to its lower surface area leading to lower hydrogenation activity, but more selective to the desired product. The successful commercialization of the new route for sertraline synthesis demonstrates that for a stereoselective hydrogenation reaction, improve product selectivity can be achieved by proper selection of catalyst support. 

Intermolecular cyclopropanation of olefins poses two stereochemical problems enantioface selection and diastereoselection (trans-cis selection). In general, for stereochemical reasons, the formation of /ra ,v-cyclopropane is kinetically more favored than that of cis-cyclopropane, and the asymmetric cyclopropanation so far developed is mostly /ram-selective, except for a few examples. Copper, rhodium, ruthenium, and cobalt complexes have mainly been used as the catalysts for asymmetric intermolecular cyclopropanation. 

A comparative experiment, using WF6/RA1C12 catalyst at Al/W = 1 and Al/W = 5, was carried out at room temperature on a cyclopentene/ 2-pentene mixture (molar ratio of 500/1). The results are summarized in Table II. Notice that the observed molecular weights approach the expected values as the cis selectivity of the catalyst is reduced. 

Table III presents additional cyclopentene polymerization data with 1-pentene as a regulator at 0°C throughout a wide range of conversion. As long as the cis selectivity is maintained, the regulator remains inactive and does not participate in the scrambling process.

In contrast, cis-selective metathesis proceeds by a three-ligand sequence ... 

In summary, the interrelation of cis-selective catalysts and their lack of metathesis activity with acyclic olefins are rationalized by a speculative scheme that incorporates the concept of a tridentate cagelike complex as the active species of cis-directing catalysts. 

An interesting stereochemical profile of this cyclization is that in the five-membered product structures, substituents PhS and OH groups are placed cis to each other, whereas in six-membered products the placement is trans (Table 6, entry 7). The cis selectivity in the five-membered ring systems is not affected by a and fi-substituents of the alkoxides (entries 2, 3 and 4), indicating that the steric effect is not the dominant factor. Instead, interaction between the oxido and carbene center composes a five- (or seven-) membered transition state 28, which allows the carbene to abstract the nearest quasi axial hydrogen as a hydride to produce a carbonyl intermediate 29, leading to the cyclization products 27 and 30 (Scheme 13, Eq. 1). Similarly, the stereoselective stepwise cyclization of cis- and rra s-2-(3,3-dithiopropyl)cyclohexanol to 2-phenylthio-... 

A novel Ru precursor and a new reaction system had to be found because the classical Ru complexes and conditions for the hydrogenation of C=C bonds did not work. Besides the enantioselectivity, chemo- and cis-selectivity and activity problems (tetrasubstituted C=C) were solved on a very good level. A broad screening of Ru catalysts (partly in collaboration with Solvias) showed that selected Josiphos ligands and DuPhos satisfied the prerequisites (see Table 37.4). 

Replacement of the triphenyl group by trialkyl groups increases the trans-selectivity, but increase in the bulk of the customary phenyl groups can increase cis-selectivity. Tris(o,o -difluorophenyl)phosphine (m.p. 125-127°) is recommended as a replacement for triphenylphosphine in dr-selective Wittig reactions, particularly of aromatic and a,(l-unsaturated aldehydes. 

Stereocontrolled radical cyclization to furansRadical cyclization of allyl 2-haloethyl ethers such as 1 show only slight stereoselectivity. However similar cyclization, but involving a dichloromethyl radical, can be highly cis-selective, whereas cyclization involving a monochloromethyl radical is frans-selective. The... 

Seitz and co-workers102 have used Ar3Al and ArMe2Al for the cis -selective opening of 1,2-anhydroarabinose 90, obtaining compound 92 in moderate to good yield (Scheme 30). 

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