Substituted alkenes, asymmetric

Acyclic diastereoselective hydroboration,J Hydroboration-oxidation of terminal alkenes substituted at C4 by a large and a medium alkyl group can proceed asymmetrically with BH3 S(CH,)2 or, even more selectively, with thexylborane. Example ... 

Acyclic alkenes, alkyl-substituted, asymmetric hydrosilylation, 10, 828... 

On the basis of theoretical and experimental results a symmetrical mercurinium ion, with most of the positive charge on mercury, has therefore been proposed in reactions of symmetrically substituted alkenes , while asymmetrical mercurinium ions or weakly bridged mercury-substituted carbocations have been proposed when there is a substituent, such as an aryl group, on the double bond -. Finally, with substituents highly capable of stabilizing carbocations, fully open intermediates have been proposed . ... 

This method provides a straightforward access to chiral alkyl-substituted 1-alkenes via asymmetric oligomerization of propene or 1-butene. Products of this type are of interest for the synthesis of pheromones and other modestly functionalized chiral compounds. 

In addition to the examples with alkene substitution, photocycloadditions of enones containing optically active ester substituents were investigated. Irradiation of a toluene solution of cy-clopentene and the chiral enone esters 13a-c gave two types of diastereomeric adducts, cis-anti-cis 14a-c and cis-syn-cis 15a-c77. By varying the size of the chiral auxiliary R the cyclobutane ring junctions syn- vs. anri-adducts) as well as the degree of asymmetric induction is altered. It is possible to obtain high enantiomeric excesses (e.g., 79% for 15a). 

Asymmetric Dihydroxylation Reactions. A substantial amount of work has been reported on the development of the asymmetric dihydroxylation (AD) reaction as originally described by Sharpless. A greater understanding has emerged of the functional group tolerance of the AD reaction and also its applicability towards differing alkene substitution patterns. The mechanism of the AD reaction has been the subject of intense debate especially with respect to the question of whether a [2 + 2] or [3 + 2] pathway is followed, and some insightful mechanistic studies have followed from this discussion. ... 

Two years later. You and co-workers [72] reported the synthesis of (3,7-alkenyl a-amino acids via chiral phosphoric acid-catalyzed asymmetric transfer hydrogenation, which unprecedentedly reduces both the alkyne and imine moieties. It should be noted that only a tran -alkene-substituted product was observed during the reduction (Scheme 15.32, up to 94% ee). 

Scheme 10.67 Proposed model to explain the regioselectivity in the intermolecular coupling of internal alkenes with asymmetrically substituted alkynes [52].

The first, and so far only, metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction of nitrile oxides with alkenes was reported by Ukaji et al. [76, 77]. Upon treatment of allyl alcohol 45 with diethylzinc and (l ,J )-diisopropyltartrate, followed by the addition of diethylzinc and substituted hydroximoyl chlorides 46, the isoxazolidines 47 are formed with impressive enantioselectivities of up to 96% ee (Scheme 6.33) [76]. 

The Best results are obtained with cA-alkenes however, the epoxidation of tri-and tetra-substituted double bonds is also possible. Because of its versatility, the Jacobsen-Katsuki epoxidation is an important method in asymmetric synthesis. 

At the beginning of the 1970s a convenient procedure was described for converting olefins into substituted butanedioates, namely through a Pd(II)-cata-lysed bisalkoxycarbonylation reaction. So far various catalytic systems have been applied to this process, but it took twenty years before the first examples of an enantioselective bisalkoxycarbonylation of olefins were reported. Ever since, the asymmetric bisalkoxycarbonylation of alkenes catalysed by palladium complexes bearing chiral ligands has attracted much attention. The products of these reactions are important intermediates in the syntheses of pharmaceuticals such as 2-arylpropionic acids, the most important class of... 

The major problem remains control of regioselectivity in favor of the branched regioisomer. While aryl alkenes as well as heteroatom-substituted alkenes favor the chiral branched isomer, for aliphatic alkenes such an intrinsic element of regiocontrol is not available. As a matter of fact branched-selective and asymmetric hydroformylation of aliphatic alkenes stands as an unsolved problem. In this respect regio- and enantioselective hydroformy-... 

An extensive array of chiral phosphine ligands has been tested for the asymmetric rhodium-catalyzed hydroboration of aryl-substituted alkenes. It is well known that cationic Rh complexes bearing chelating phosphine ligands (e.g., dppf) result in Markovnikoff addition of HBcat to vinylarenes to afford branched boryl compounds. These can then be oxidized through to the corresponding chiral alcohol (11) (Equation (5)) ... 

However, most asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides with alkenes are carried out without Lewis acids as catalysts using either chiral alkenes or chiral auxiliary compounds (with achiral alkenes). Diverse chiral alkenes are in use, such as camphor-derived chiral N-acryloylhydrazide (195), C2-symmetric l,3-diacryloyl-2,2-dimethyl-4,5-diphenylimidazolidine, chiral 3-acryloyl-2,2-dimethyl-4-phenyloxazolidine (196, 197), sugar-based ethenyl ethers (198), acrylic esters (199, 200), C-bonded vinyl-substituted sugar (201), chirally modified vinylboronic ester derived from D-( + )-mannitol (202), (l/ )-menthyl vinyl ether (203), chiral derivatives of vinylacetic acid (204), ( )-l-ethoxy-3-fluoroalkyl-3-hydroxy-4-(4-methylphenylsulfinyl)but-1 -enes (205), enantiopure Y-oxygenated-a,P-unsaturated phenyl sulfones (206), chiral (a-oxyallyl)silanes (207), and (S )-but-3-ene-1,2-diol derivatives (208). As a chiral auxiliary, diisopropyl (i ,i )-tartrate (209, 210) has been very popular. 

An interesting antibody-catalyzed intermolecular asymmetric 1,3-dipolar cycloaddition reaction between 4-acetamidobenzonitrile N-oxide and N,N-dimethylacrylamide generating the corresponding 5-acylisoxazoline was observed (216). Reversed regioselectivity of nitrile oxide cycloaddition to a terminal alkene was reported in the reaction of 4-A rt-butylbenzonitrile oxide with 6A-acrylamido-6A-deoxy-p-cyclodextrin in aqueous solution, leading to the formation of the 4-substituted isoxazoline, in contrast to the predominance of the 5-substituted regioisomer from reactions of monosubstituted alkenes (217). 

Asymmetric Hydrosilylation of Alkyl-Substituted Acyclic Alkenes 828... 

PHENAP 65 was prepared and resolved98 in a similar manner to QUINAP 60 and tested in asymmetric rhodium-catalyzed hydroboration-oxidations." Impressive enantioselectivities were obtained and the sterically demanding cyclic substrates were hydroborated with 64-84% ee. Compared to the corresponding results obtained with diphosphine ligands, it is clear that QUINAP 60, and structural relatives 61-64 and PHENAP 65, give superior results in the asymmetric rhodium-catalyzed hydroboration of several vinylarenes, and are essentially the only practical solution for / -substituted alkenes.100 The reasons for this are not well understood, but thought to be due to the particular... 

Negishi reported the zirconium-catalyzed enantioselective carboalumination of alkenes, which consisted of a hydroalumination/alkylalumination tandem process.133-135 This permits the asymmetric syntheses of methyl-substituted alkanols and other derivatives, typically with >90% ee, which represents an increase in ee value by 15% from the previously obtained 70-80%.136-138 The hydroalumination/zirconium-catalyzed enantioselective carboalumination of alkenes was carried out using (—)-bis(neomenthylindenyl)zirconium dichloride as the catalyst (Table 15).133... 

In the case of tri-substituted alkenes, the 1,3-syn products are formed in moderate to high diastereoselectivities (Table 21.10, entries 6—12). The stereochemistry of hydrogenation of homoallylic alcohols with a trisubstituted olefin unit is governed by the stereochemistry of the homoallylic hydroxy group, the stereogenic center at the allyl position, and the geometry of the double bond (Scheme 21.4). In entries 8 to 10 of Table 21.10, the product of 1,3-syn structure is formed in more than 90% d.e. with a cationic rhodium catalyst. The stereochemistry of the products in entries 10 to 12 shows that it is the stereogenic center at the allylic position which dictates the sense of asymmetric induction... 

Enantioselective hydrogenation of 1,6-enynes using chirally modified cationic rhodium precatalysts enables enantioselective reductive cyclization to afford alky-lidene-substituted carbocycles and heterocycles [27 b, 41, 42]. Good to excellent yields and exceptional levels of asymmetric induction are observed across a structurally diverse set of substrates. For systems that embody 1,2-disubstituted alkenes, competitive /9-hydride elimination en route to products of cycloisomerization is observed. However, related enone-containing substrates cannot engage in /9-hydride elimination, and undergo reductive cyclization in good yield (Table 22.12). 

---