Double bonds asymmetric transfer

Notice that although there are four asymmetric centers in the molecule, one isomer is formed in 58% yield. This points to a concerted cyclization step in which the stereochemistry incorporated in the C==C double bonds is transferred to the developing asymmetric centers in the product. (This phenomenon is analogous to the well-known stereospecific formation of the steroid skeleton by cationic cyclizations of similar olefinic systems with defined stereochemistry at the C—C double bonds.)... 

Efficient asymmetric transfer is also observed for 1,2-benzenediol induced reactions of a-sub-stituted (Z)- and ( ,)-allyl(trialkoxy)silanes prepared by hydrosilation of conjugated dienes, although in this case the electrophile attacks the C-C double bond of the allylsilane syn with... 

It may be of interest to note that the stereospecific transformation shown in equation 15 has been cited as the first reported observation of an 1 - 3 chirality transfer. It is evident that on rearrangement of optically active 6d to 7d, the chiral center at C-a is eliminated and a new one created at C-y. The term self-immolative asymmetric synthesis has also been used to describe syntheses of this kind. As pointed out by Hoffmann , quantitative 1 - 3 chirality transfer will follow from the suprafacial - course of rearrangement, provided the reactant has a uniform configuration at the j8, y-double bond. This stereochemical prediction has also been confirmed by the results obtained in several other [2,3]sigmatropic rearrangements, subsequently reported " . 

In this chapter and in Chapters 10-12, we will review and validate some methods for asymmetric (transfer) hydrogenation of carbon-oxygen and carbon-carbon double bonds catalysed by non-metallic systems, homogeneous transition metal catalysts and biocatalysts. Reduction of carbon-nitrogen double bond systems will be reported in another volume of this series. 

Photodimerization of cinnamic acids and its derivatives generally proceeds with high efficiency in the crystal (176), but very inefficiently in fluid phases (177). This low efficiency in the latter phases is apparently due to the rapid deactivation of excited monomers in such phases. However, in systems in which pairs of molecules are constrained so that potentially reactive double bonds are close to one another, the reaction may proceed in reasonable yield even in fluid and disordered states. The major practical application has been for production of photoresists, that is, insoluble photoformed polymers used for image-transfer systems (printed circuits, lithography, etc.) (178). Another application, of more interest here, is the use that has been made of mono- and dicinnamates for asymmetric synthesis (179), in studies of molecular association (180), and in the mapping of the geometry of complex molecules in fluid phases (181). In all of these it is tacitly assumed that there is quasi-topochemical control in other words, that the stereochemistry of the cyclobutane dimer is related to the prereaction geometry of the monomers in the same way as for the solid-state processes. 

BINAP has been extensively used for the asymmetric hydrogenation, transfer hydrogenation and isomerisation of double bonds using both ruthenium and rhodium complexes. 

Combination of the Hantzsch ester mediated transfer hydrogenation together with chlorine (116) or fluorine (117) electrophiles allows for the formal addition of HCl or HF aaoss a double bond in a catalytic asymmetric manner (Scheme 48) [178], Within this paper the reactions were further refined by the use of two cycle-specific secondary amines which effectively operated independently within the same reaction mixture. Impressively, this allowed access to either diastereoisomer of the product depending upon the absolute configuration of the catalyst used in the second step of the sequence. 

Table 17) with two substituents in position C3 the oxygen transfer by the chiral hydroperoxides occurred from the same enantioface of the double bond, while epoxidation of the (ii)-phenyl-substituted substrates 142c,g,i resulted in the formation of the opposite epoxide enantiomer in excess. In 2000 Hamann and coworkers reported a new saturated protected carbohydrate hydroperoxide 69b , which showed high asymmetric induction in the vanadium-catalyzed epoxidation reaction of 3-methyl-2-buten-l-ol. The ee of 90% obtained was a milestone in the field of stereoselective oxygen transfer with optically active hydroperoxides. Unfortunately, the tertiary allylic alcohol 2-methyl-3-buten-2-ol was epoxidized with low enantioselectivity (ee 18%) with the same catalytic system . 

Neutral cyclodextrins have been used as chiral phase-transfer catalysts for an interesting inverse phase-transfer catalysis reaction [50]. The Markovnikovhydration of the double bond by an oxymercuration-demercuration reaction has been demonstrated in the presence of cyclodextrins as chiral phase-transfer catalysts to obtain products in low to moderate enantioselectivity (Scheme 7.16). The mercuric salts are water-soluble, and remain in the aqueous phase, whereas the neutral alkenes prefer an organic phase. A neutral cyclodextrin helps to bring the alkenes into the aqueous phase in a biphasic reaction, and also provides the necessary asymmetric environment. 

As discussed in Section 10.1, asymmetric epoxidation of C=C double bonds usually requires electrophilic oxygen donors such as dioxiranes or oxaziridinium ions. The oxidants typically used for enone epoxidation are, on the other hand, nucleophilic in nature. A prominent example is the well-known Weitz-Scheffer epoxidation using alkaline hydrogen peroxide or hydroperoxides in the presence of base. Asymmetric epoxidation of enones and enoates has been achieved both with metal-containing catalysts and with metal-free systems [52-55]. In the (metal-based) approaches of Enders [56, 57], Jackson [58, 59], and Shibasaki [60, 61] enantiomeric excesses > 90% have been achieved for a variety of substrate classes. In this field, however, the same is also true for metal-free catalysts. Chiral dioxiranes will be discussed in Section 10.2.1, peptide catalysts in Section 10.2.2, and phase-transfer catalysts in Section 10.2.3. 

Asymmetric nucleophilic addition to C=C double bonds (see also Chapter 4) can also proceed highly stereoselectively. Several examples of enantio- and diastereo-selective Michael additions with 99% ee for the resulting products have been described by the Corey group [19]. A cinchonidine-derived phase-transfer organo-catalyst (10 mol%) was used. 

The geometrical isomers and enantiomers of the overcrowded alkenes 15-18 can readily be separated using chiral HPLC. Recently, an asymmetric synthesis of overcrowded alkenes has been developed, involving chirality transfer from an axial single bond to an axial double bond (Scheme 8).32 This methodology is particularly attractive for preparation of larger quantities of enantiomerically pure chiral switches based on overcrowded alkenes. The orientation of the two xanthylidene moieties is dictated by a binaphthol template. After a coupling step and separation of the diastereomers, the bi-xanthylidene is obtained with 96 % e.e. after removal of the template. 

Fig. 10.24. Asymmetric carbonyl group reduction with Alpine-Borane (preparation Figure 3.27 for the "parachute-like" notation of the 9-BBN part of this reagent see Figure 3.21). The hydrogen atom that is in the cis-position to the boron atom (which applies to both ft- and /T-H) and that after removal of the reducing agent leaves behind a tri- instead of a disubstituted C=C double bond (which applies to ft-, but not / -H) is transferred as a hydride equivalent. In regard to the reduction product depicted in the top row, the designation S of the configuration relates to the aryl-substituted and R to the Rtert-substituted propargylic alcohol.

As a consequence of the restricted jump-rope rotation around the trans double bond, (i j-cyclo-octene 38E is chiral. Optically active (E)-cyclo-octene has long been known, but the conventional multistep synthesis is rather tedious [138-140]. In contrast, direct-preparation of optically active (Ej-cyclo-octene through asymmetric photosensitization is an attractive alternative. The first enantiodifferentiating Z-E photoisomerization of cyclo-octene 38Z sensitized by simple chiral alkyl benzenecarboxylates was reported in 1978 to give low enantiomeric excesses (ee s) of <6% [141] a variety of systems and conditions have been examined since then to raise the product ee. For an efficient transfer of chiral information... 

Addition reactions to unsym metric olefins in which a reagent with the structure H—X transfers the H atom to the less-substituted C atom and the X group to the more-substituted C atom give, according to an old nomenclature, a so-called Markovnikov addition product On the other hand, addition reactions of reagents H—X in which the H atom is transferred to the more substituted C atom of an asymmetrically substituted C=C double bond and the X group is transferred to the less substituted C atom lead to a so-called anti-Markovnikov addition product. 

The AA reaction is closely related to the asymmetric dihydroxylation (AD). Alkenes are enantioselectively converted to protected 3-aminoalcohols (Scheme 1) by syn-addition of osmium salts under the influence of the chirr 1 bis-Cinchona ligands known from the AD process (see Chap. 20.1). As for the AD reaction, a cooxidant is needed to regenerate the active osmium species. But in the AA process the cooxidant also functions as the nitrogen source. Since two different heteroatoms are transferred to the double bond, regioselectivity becomes an important selectivity issue in addition to enantioselectivity. Moreover, chemoselectivity has to be addressed due to the possible formation of the... 

In addition, allenes can act as the olefinic part of the reaction [32], Al-lenynes like 12 may react with both double bonds. Brummond established the substitution patterns for the reaction with either the external or the internal bond of the allenic fragment, that give products with different ring sizes (13— 14) [33]. This group has applied these studies to the synthesis of hydroxy-methylfulvalene (17), a potent anticancer agent related with illudines, a natural sesquiterpene family. The key step was the synthesis of 16 from 15 with a PKR mediated by molybdenum carbonyl (Scheme 6) [34,35]. In addition they have developed an asymmetric version of the reaction. They have transferred efficiently chirality from a non-racemic allene to an a-alkylidene and an a-silylidene cyclopentenone in a molybdenum mediated reaction [36-38]. 

The mechanism of the asymmetric epoxidation of allylic alcohols with the Sharpless-Katsuki catalyst is assumed to be very similar to the one described for the Halcon-ARCO process in Section 2.5. The key point is that the chiral tartrate creates an asymmetric environment about the titanium center (Figure 18). When the allylic alcohol and the t-butyl hydroperoxide bind through displacement of alkoxy groups from the metal, they are disposed in such a way as to direct oxygen transfer to a specific face of the C=C double bond. This point is crucial to maximize enantioselectivity. 

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