Asymmetric olefins, addition

Other interesting electron-deficient olefin substrates for the asymmetric conjugate addition include cr-acet-amidoacrylic ester SI,101 dimethyl itaconate S2,114 ct,/3-unsaturated sulfones S3,115 and alkenylphosphonate S4116 (Figure 8). 

Recently considerable attention has been given to chiral 72-bonded olefin spectator ligands for the asymmetric conjugate addition.122 Hayashi and Carreira independently reported that new chiral diene ligands 83,123 84,124 and 85125 showed high enantioselectivities in Rh(i)-catalyzed conjugate addition of arylboronic acids to enones (Scheme 41). 

Scheme 21. Zr-catalyzed asymmetric olefin alkylation is used in conjunction with Pd-catalyzed addition of an arylox-ide to an epoxide and Mo-catalyzed olefin metatheses in Hoveyda s total synthesis of nebivolol (1998).

Synthetic applications of the asymmetric Birch reduction and reduction-alkylation are reported. Synthetically useful chiral Intermediates have been obtained from chiral 2-alkoxy-, 2-alkyl-, 2-aryl- and 2-trialkylsllyl-benzamides I and the pyrrolobenzodlazeplne-5,ll-diones II. The availability of a wide range of substituents on the precursor benzoic acid derivative, the uniformly high degree of dlastereoselection in the chiral enolate alkylation step, and the opportunity for further development of stereogenic centers by way of olefin addition reactions make this method unusually versatile for the asymmetric synthesis of natural products and related materials. 

Chen and co-workers utilized the chiral bifunctional catalysts to directly access vinylogous carbon-carbon bonds via the asymmetric Michael addition of a,a-dicy-ano-olefms to nitro-olefms [102]. The scope of the reaction was explored with a variety of substituted a,a-dicyano-olefins and P-substituted nitro-olefms (Scheme 50). The authors propose the catalysf s tertiary amine functionality depro-tonates the cyano-olefm, activating the nucleophile to add to the -face of the pre-coordinated nitro-olefm. 

Rhodium-catalyzed asymmetric conjugate addition has enjoyed uninterrupted prosperity since the first report by Hayashi and Miyaura [6]. Its high enantioselectivity and wide applicability are truly remarkable. However, some problems still remain, since the carbon atoms that can be successfully introduced by this rhodium-catalyzed reaction have been limited to sp carbons and the substrates employed have been limited mostly to the electron-deficient olefins free from sterically bulky substituents at a- and / -positions. These issues will be the subject of increasing attention in the future. 

One of the landmark achievements in the area of enantioselective catalysis has been the development of a large-scale commercial application of the Rh(I)/BINAP-catalyzed asymmetric isomerization of allylic amines to enamines. Unfortunately, methods for the isomerization of other families of olefins have not yet reached a comparable level of sophistication. However, since the early 1990s promising catalyst systems have been described for enantioselective isomerizations of allylic alcohols and aUylic ethers. In view of the utility of catalytic asymmetric olefin isomerization reactions, I have no doubt that the coming years will witness additional exciting progress in the development of highly effective catalysts for these and related substrates. 

Arcus, C. L., and D. G. Smyth Olefinic additions with asymmetric reactants. Part. III. The resolution and addition reactions of 3-ethylhept-3-en-2-ol. A partial asymmetric synthesis effected by hydrogenation. J. chem. Soc. [London] 1955, 34. 

The asymmetric Michael addition of active methylene or methine compounds to electron-deficient olefins, particularly o,[l-unsaturated carbonyl compounds, represents a fundamental - yet useful - approach to construct functionalized carbon frameworks [36]. 

The hydroboration of asymmetrical olefins thus gives monoalkylboranes (addition... 

Fig. 3.39. Regioselective methanol addition to an asymmetric olefin via solvomercuration/ reduction.

Preparatively it is important that mineral acids, carboxylic acids, and ferf-carbenium ions can be added to olefins via carbenium ion intermediates. Because of their relatively low stability, primary carbenium ions form more slowly in the course of such reactions than the more stable secondary carbenium ions, and these form more slowly than the even more stable tertiary carbenium ions (Hammond postulate ). Therefore, mineral and carboxylic acids add to asymmetric olefins regioselectively to give Markovnikov products (see Section 3.3.3 for an explanation of this term). In addition, these electrophiles add most rapidly to those olefins from which tertiary carbenium ion intermediates can be derived. 

Unlike the addition of halogens across double bonds, addition of acids results in formation of asymmetrical products. Specifically, a different group is added to each side of the double bond. Thus, if this reaction is applied to asymmetrical olefins such as propene, multiple products might be expected to form as illustrated in Scheme 7.8. In fact, while a mixture of products is formed, there is an overwhelming presence of the secondary substituted product compared to that with substitution at the primary position. This preference of reaction products resulting from addition of protic acids across double bonds is governed by Markovnikov s rule. 

Although it is known that free radicals add predominantly to the least substituted end of an olefinic double bond there is very little quantitative information on the relative rate of addition at the two positions in asymmetric olefins (Cadogan and Hey, 1954 Cvetanovid, 1963). The rotating cryostat has been used to examine this aspect for the case of the addition of hydrogen atoms to a variety of olefins deposited in a matrix of adamantane. The ratios of the rates of addition are given in Table 7, and for illustration the reaction with propylene is considered below. 

Carbene transfer from the silver(I) complex is not only possible to ruthenium(II) to form a catalyst suitable for asymmetric olefin metathesis, but also to copper(I) [17]. This provides a catalyst suitable for copper(I) catalysed conjugate addition of alkyl- and arylzinc reagents to P-substituted cyclic enones. The products, chiral cyclic ketones, are obtained in 88-95% isolated yield and 67-83% ee. 

The asymmetric Michael addition of active methylene or methyne compounds to electron deficient olefins, particularly a,P-unsaturated carbonyl compounds, represents a fundamental and useful approach to construct functionalized carbon frameworks [51]. The first successful, phase-transfer-catalyzed process was based on the use of well-designed chiral crown ethers 69 and 70 as catalyst. In the presence of 69, P-keto ester 65 was added to methyl vinyl ketone (MVK) in moderate yield but with virtually complete stereochemical control. In much the same way, crown 70 was shown to be effective for the reaction of methyl 2-phenylpropionate 67 with methyl acrylate, affording the Michael adduct 68 in 80% yield and 83% ee (Scheme 11.15) [52]. 

The continued fascination chemists possess with asymmetric synthesis provides the basis for the next four procedures. The synthesis of (R)-(-)-10-METHYL-l(9)-OCTALONE-2 is a nice demonstration of an asymmetric Michael addition by a chiral imine followed by an aldol—in short an asymmetric Robinson annulation. The asymmetric glycolization to STILBENE DIOL (R,R-l,2-DIPHENYL-I,2-ETHANEDIOL) represents an olefin oxidation using catalytic alkaloids in tandem with osmium tetroxide. As reagents for a variety of asymmetric alkylations, the preparation of 2-CYANO-6-PHENYLOXAZOLOPIPERIDINK is pavscnicd as well as another route to... 

Naproxen. In addition, the use of chiral bisphosphites in asymmetric olefin hy-drocyanation is described. Details of the structural features responsible for hi b/1 and %ee in asymmetric hydroformylation and hydrocyanation are presented. 

In addition to the configurational isomerism encountered in polymers derived from asymmetric olefins, geometric isomerism is obtained when conjugated dienes are polymerized, e.g., (CH2=CX—CH=CH2). Chain growth from monomers of this type can proceed in a number of ways, illustrated conveniently by 2-methyl-1,3-butadiene (isoprene). Addition can take place either through a 1,2-mechanism or a 3,4-mech-anism, both of which could lead to isotactic, syndiotactic, or atactic structures, or by a 1,4-mode leaving the site of unsaturation in the chain. 

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