1.3- Dienes, prochiral

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. 

In a similar manner, butadienyl phenylacetate 71, an achiral diene, is expected to approach the chiral dienophile (R)-10 from its Re-prochiral face. The two faces of the chelate ring are differentiated by the small hydrogen and large benzyl groups attached to the chiral center of (R)-10 (Scheme 1-18) the ratio of the Si attack product to the Re attack product is 1 8.88... 

For diene ligands which are prochiral, complexation results in the formation of a racemic mixture. Resolution of this racemic mixture has been accomplished via either classical methods102, chromatographic separation on chiral stationary phases103 or kinetic resolution104. For certain acyclic or cyclic dienes possessing a pendent chiral center(s)... 

The present titanium reagent was noted to exhibit a wide applicability to the asymmetric Diels-Alder reaction of various prochiral dienes and dienophiles. 

Amir H. Hoveyda of Boston College has reported (J. Am. Chem. Soc. 2005,127, 8526) the development of a family of chiral Mo metathesis catalysts that convert prochiral dienes such as 5 and 8... 

Certain chiral organic compounds create crystalline environments and act as enantio-controlling media (7) even though they do not function as true catalysts. Natta s asymmetric reaction of prochiral trans-1,3-pentadiene, which was included in the crystal lattice of chiral perhydro-triphenylene as a host compound, to form an optically active, isotactic polymer on 7-ray irradiation, is a classic example of such a chiral molecular lattice (Scheme 1) (2). Weak van der Waals forces cause a geometric arrangement of the diene monomer that favors one of the possible enantiomeric sequences. 

The chiral boron complex prepared in situ from chiral binaphthol and B(OPh)3 is utilized for the asymmetric aza-Diels-Alder reaction of Danishefsky s diene and imines [67] (Eq. 8A.43). Although the asymmetric reaction of prochiral imine affords products with up to 90% ee, the double asymmetric induction with chiral imine by using oc-benzylamine as a chiral auxiliary has achieved almost complete diastereoselectivity for both aliphatic and aromatic aldimines. This method has been successfully applied to the efficient asymmetric synthesis of anabasine and coniine of piperidine alkaloides. 

Desymmetrization of an achiral, symmetrical molecule through a catalytic process is a potentially powerful but relatively unexplored concept for asymmetric synthesis. Whereas the ability of enzymes to differentiate enantiotopic functional groups is well-known [27], little has been explored on a similar ability of non-enzymatic catalysts, particularly for C-C bond-forming processes. The asymmetric desymmetrization through the catalytic glyoxylate-ene reaction of prochiral ene substrates with planar symmetry provides an efficient access to remote [28] and internal [29] asymmetric induction (Scheme 8C.10) [30]. The (2/ ,5S)-s> i-product is obtained with >99% ee and >99% diastereoselectivity. The diene thus obtained can be transformed to a more functionalized compound in a regioselective and diastereoselective manner. 

Asymmetric hydrosilylation of prochiral carbonyl compounds, imines, alkenes and 1,3-dienes has been extensively studied and continues to be one of the most important subjects in the hydrosilylation reactions. This topic has been reviewed at each stage of its development as a useful synthetic method based on asymmetric catalytic processes1,3,187-189. In the last decade, however, substantial progress has been made in the efficiency of this reaction. Accordingly, this section summarizes the recent advances in this reaction. 

The catalytic system described above has been further developed to an asymmetric catalytic complexation of prochiral 1,3-dienes (99% yield, up to 86% ee) using an optically active camphor-derived 1-azabutadiene ligand [56]. This method provides for the first time planar-chiral transition metal 7t-complexes by asymmetric catalysis. 

Hydrogenation of dienes with up to 20 1.0 diastereoselectivity and 99% ee is mediated by carbene complexes. The scope and limitations of these reactions were investigated.288 Asymmetric transfer hydrogenation to prochiral ketones, catalysed by a Ru(II) complex (10) or its dimer, with formic acid-triethylamine has been reported, (0 The protocol leads to high yields and enantioselectivity up to 96%. It has been suggested that 16-electron Ru(II) and the Ru-H intermediates are involved in this reaction.289... 

In the reaction between an activated diene and a prochiral aldehyde, which is catalyzed by chiral Lewis acids, 5,6-dihydropyranoncs such as 6 are formed enantiomerically enriched. By attachment of a chiral auxiliary (3-heptafluorobutanoyl camphor derivatives such as 7 to a soluble poly-siloxane by hydrosilylation the catalyst should be recyled easily by precipitation or ultrafiltration while the cycloaddition reaction can be performed in homogeneous solution [lOj. 

As with acyclic dienes, methods have been developed for enantioselective and diastereoselective complexation of prochiral and chiral cyclic dienes. An approach has been developed for the asymmetric catalytic complexation of prochiral eyelohexa-1,3-dienes nsing (1) in the presence of catalytic amounts of l-azabuta-l,3-dienes such as (232) or (233) an enantiomeric excess as high as 86% has been reported. By contrast, attempts to effect diastereoselective complexations using cyclic diene systems eqnipped with chiral auxiliaries have met with limited success. On the other hand, direct complexation of chiral cyclic dienes snch as (234) and (235) proceed with a high degree of diastereoselectivity, where the iron tricarbonyl fragment is directed syn to alcohols or ethers by transient coordination ( heteroatom dehvery ) (Scheme 66). ... 

Tridentate salen ligands (10) derived from 1 have given excellent results in the enantiocontrol of the hetero Diels-Alder addition reaction of dienes with aldehydes (eq 7) and in the asymmetric additions of TMS-azide to mc5o-epoxide and trimethylsilyl cyanide to benzaldehyde (up to 85% ee). Phosphino-oxazolines derived from 1 have been employed for the asymmetric control of palladium-catalyzed allylic substitution reactions products of 70-90% ee were obtained. Photolysis of crystalline adducts of enantiomerically pure 1 with prochiral alcohols results in asymmetric inductions of up to 79% in a rare example of a solid-state enantioselective reaction. ... 

The asymmetric glyoxylate-ene reactions have been exploited in the total synthesis of (—)-specionin, which involves asymmetric desymmetrization of a prochiral diene (eq 3), and (—)-xylomollin, which involves an efficient kinetic resolution of a racemic diene (eq4).i - ... 

The factors which direct the diene to the top (Ca re) or bottom face (Ca si) of dienophile (XXXI) may be of steric and/or stereoelectronic origin. Moreover, the overall stereofacial bias is intrinsically dependent on the conformation of (XXXI). Thus the rotational freedom around the single bonds which link the chiral and prochiral centers in (XXXI) needs to be restricted in a well-defined manner. 

Asymmetric Diels-Alder reactions of dienes substituted widi a removable chiral moiety with prochiral dienophiles have been much less extensively studied. Hie few successful examples involve ester or ether derivatives of 1,3-dienols. 

At first sight, the use of a chiral catalyst appears to be the potentially most attractive method to achieve asymmetric Diels-Alder reactions of prochiral dienes and dienophiles. Compared to the stoichiometric use of a covalently attached auxiliary, two synthetic steps would be avoided. However, analysis of the resulting enantiomer mixture and purification of the major product may be more laborious. 

We have recently reported not only the first examples of enantioselective reactions of dienes, with have prochiral centers, and acetylenic aldehydes catalyzed by CAB 2, BLA 4, and BLA 6, but also an ab initio study which supports the predominance of an exo transition structure, thus clarifying the origin of the enantioselectivity observed upon catalysis [27c]. 

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