Prochiral alkene

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

Asymmetric Hydroboration. Hydroboration—oxidation of (Z)-2-butene with diisopinocampheylborane was the first highly enantioselective asymmetric synthesis (496) the product was R(—)2-butanol in 87% ee. Since then several asymmetric hydroborating agents have been developed. Enantioselectivity in the hydroboration of significant classes of prochiral alkenes with representative asymmetric hydroborating agents is shown in Table 3. 

Table 3. Enantioselectivity in the Hydroboration of Prochiral Alkenes with Various Hydroborating Agents ...

An efficient general synthesis of a-chiral (Z)- and (H)-a1kenes ia high enantiomeric purity is based on the hydroboration of alkynes and 1-bromoaIkynes, respectively, with enantiomericaHy pure IpcR BH readily available by the hydroboration of prochiral alkenes with monoisopiaocampheylborane, followed by crystallization (519). 

Diboration of terminal alkenes has also been studied with other d " metals (Fig. 2.12) including the Ag and Au complexes 75-77 and the Pt" complexes 78-79. Styrene is diborylated with 100% selectivity and good conversions in THF (46% for 75 and 94% for 77 at 5 mol%, 60 h) using equimolecular amounts of (Bcat)j. The difference in activity between the Ag and Au complexes has been ascribed to the increased lability of the Ag-NHC bond, which may lead to catalyst decomposition under the reaction conditions, hi both catalytic systems it is believed that the active species involves only one coordinated NHC ligand. Complex 77 is less active than 74 and 75, possibly due to steric reasons. The enantioselectivity of 77 in the diboration of prochiral alkenes is very low [63]. 

Monoisocampheylborane (IpcBH2) can be prepared in enantiomerically pure form by purification of a TMEDA adduct.202 When this monoalkylborane reacts with a prochiral alkene, one of the diastereomeric products is normally formed in excess and can be obtained in high enantiomeric purity by an appropriate separation.203 Oxidation of the borane then provides the corresponding alcohol having the enantiomeric purity achieved for the borane. 

The cA-PtCl2(diphosphine)/SnCl2 constitutes the system mostly used in catalyzed hydroformylation of alkenes and many diphosphines have been tested. In the 1980s, Stille and co-workers reported on the preparation of platinum complexes with chiral diphosphines related to BPPM (82) and (83) and their activity in asymmetric hydroformylation of a variety of prochiral alkenes.312-314 Although the branched/normal ratios were low (0.5), ees in the range 70-80% were achieved in the hydroformylation of styrene and related substrates. When the hydroformylation of styrene, 2-ethenyl-6-methoxynaphthalene, and vinyl acetate with [(-)-BPPM]PtCl2-SnCl2 were carried out in the presence of triethyl orthoformate, enantiomerically pure acetals were obtained. 

Although the latter product is a solvated mononuclear [Rh(MeOH)2(diphos)]+ cation, in the solid state it is isolated as a binuclear complex of formula [Rh2 (diphos)2](BF4)2, in which each rhodium center is bonded to two phosphorus atoms of a chelating bis(diphenylphosphino)ethane ligand, and to a phenyl ring of the bis(diphenylphosphino)ethane ligand of the other rhodium atom. This dimer reverts to a mononuclear species on redissolving. The mechanism of hydrogenation of the prochiral alkene methyl(Z)-a-acetamidocinnamate, studied in detail by Halpern [31], is depicted in Scheme 1.7. 

In 1968, Knowles et al. [1] and Horner et al. [2] independently reported the use of a chiral, enantiomerically enriched, monodentate phosphine ligand in the rhodium-catalyzed homogeneous hydrogenation of a prochiral alkene (Scheme 28.1). Although enantioselectivities were low, this demonstrated the transformation of Wilkinson s catalyst, Rh(PPh3)3Cl [3] into an enantioselective homogeneous hydrogenation catalyst [4]. 

In the literature it has been generally assumed that hydrogenation of the spectator dienes with cationic Rh(I)-complexes [13] proceeds rapidly before the hydrogenation of the prochiral alkene. These induction periods, which were found in many hydrogenation reactions, however, prove without doubt the slower hydrogenation of the dienes. 

The results of this experiment prove unequivocally that, in addition to the substrate complex, the diene complex is present throughout the hydrogenation reaction. Even after 500 turnovers of the prochiral alkene, unchanged COD precatalyst is still present in solution. 

The published quantification of the rate of hydrogenation of the dienes COD and NBD of a large number of cationic rhodium(I) chelate complexes allows a good estimation of expected effects on the rate of enantioselective hydrogenation of prochiral alkenes. From the first-order pseudo-rate constants the time needed for complete hydrogenation of the diene introduced as part of the rhodium precursor can be easily calculated as six- to seven-fold the half life. It is recommended that the transfer into the solvent complex be followed by NMR spectroscopy. 

The data in Table 6.7 illustrate that when the non-racemic (ebthi)Zr system is used to catalyze the hydrogenation of prochiral alkenes, moderate levels of enantiofacial differentiation are observed (23—65% ee). Enantioselective deuteration of pentene occurs in low yield but shows noticeable enantioselection (23% ee). The same reaction with styrene proceeds in 61% yield and with moderate enantioselectivity (65% ee). Hydrogenation of 2-phenyl-l-pentene proceeds in excellent yield but with poor control of stereochemistry (95% yield, 36% ee). 

Prochem Maxflo T agitator, 7 739 Prochiral alkenes, hydroboration of, 73 665-666... 

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

Roberts and co-workers have employed a number of chiral carbohydrate-derived thiols as polarity reversal catalysts in the radical hydrosilylation of electron-rich prochiral alkenes [68-70]. In these thiols, the SH group is attached to the anomeric carbon atom. Scheme 21 demonstrates the non-catalyzed reaction and in step b, the hydrogen atom transfer from the silane... 

When the diphosphine is chiral, binding of a prochiral alkene creates diastereomeric catalyst-alkene adducts. (Diastereomers result because binding of a prochiral alkene to a metal center generates a stereogenic center at the site of unsaturation.) Through a powerful combination of3lP and l3C NMR methods, Brown and Chaloner first demonstrated the presence of two diastereomeric catalyst-enamide adducts with bidentate coordination of the substrate to the metal (Figure 1) [19]. 

In the case of prochiral alkenes the dihydroxylation reaction creates new chiral centers in the products and the development of the asymmetric version of the reaction by Sharpless was one of the very important accomplishments of the last years. He received the Nobel Price in Chemistry 2001 for the development of catalytic oxidation reactions to alkenes. 

Kinetic data on the influence of the reaction temperature on the enantioselectivity using chiral bases and prochiral alkenes revealed a nonlinearity of the modified Eyring plot [16]. The observed change in the linearity and the existence of an inversion point indicated that two different transition states are involved, inconsistent with a concerted [3+2] mechanism. Sharpless therefore renewed the postulate of a reversibly formed oxetane intermediate followed by irreversible rearrangement to the product. 

When a chiral metal complex forms a complex with a prochiral alkene , either because it contains a chiral ligand or a chiral metal centre, the resulting complex is a diastereomer. Thus, a mixture of diastereomers can form when the chiral complex coordinates to both faces of the alkene. As usual, these diastereomers have different properties and can be separated. Or, more interestingly, in the catalytic reactions below, the two diastereomers are formed in different amounts and their reactivities are different as well. 

BINAP was introduced by Noyori [18], It has been particularly explored for reduction with ruthenium catalysts. While the first generation rhodium catalysts exhibited excellent performance with dehydroamino acids (or esters), the second generation of hydrogenation catalysts, those based on ruthenium /BINAP complexes, are also highly enantioselective for other prochiral alkenes. An impressive list of rather complex organic molecules has been hydrogenated with high e.e. s. 

As we have seen above polymerisation of all prochiral alkenes produces a new stereogenic centre for each monomer inserted. In a site-controlled... 

The stoichiometric enantioselective reaction of alkenes and osmium tetroxide was reported in 1980 by Hentges and Sharpless [17], As pyridine was known to accelerate the reaction, initial efforts concentrated on the use of pyridine substituted with chiral groups, such as /-2-(2-menthyl)pyridine but e.e. s were below 18%. Besides, it was found that complexation was weak between pyridine and osmium. Griffith and coworkers reported that tertiary bridgehead amines, such as quinuclidine, formed much more stable complexes and this led Sharpless and coworkers to test this ligand type for the reaction of 0s04 and prochiral alkenes. 

Reactions of alkenes such as 120 with a-chloronitrosoalkanes of type 119 proceed under very mild conditions and result in the formation of nitrones 121 that can be easily hydrolyzed into hydroxylamines 122 (equation 86) . Chiral carbohydrate-derived a-chloronitrosoalkenes 123 possess enhanced reactivity and produce good stereoselectivity in reaction with prochiral alkenes such as 124 (equation 87) . ... 

The enantioselective epoxidation of prochiral alkenes with an aldehyde dioxirane was achieved by Bez and Zhao . ... 

The dioxirane epoxidation of a prochrral alkene will produce an epoxide with either one new chirality center for terminal alkenes, or two for internal aUcenes. When an optically active dioxirane is nsed as the oxidant, expectedly, prochiral alkenes should be epoxi-dized asymmetrically. This attractive idea for preparative purposes was initially explored by Curci and coworkers in the very beginning of dioxirane chemistry. The optically active chiral ketones 1 and 2 were employed as the dioxirane precursors, but quite disappointing enantioselectivities were obtained. Subsequently, the glucose-derived ketone 3 was used, but unfortunately, this oxidatively labile dioxirane precursor was quickly consumed without any conversion of the aUcene . After a long pause (11 years) of activity in this challenging area, the Curci group reported work on the much more reactive ketone... 

Fe(lll) masking, 669 low-density lipoprotein antioxidant, 611 Prochiral alkenes... 

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