Alkenes axially chiral

Various acetylenes having functional groups such as halide, alcohol, ether, amine, alkene and nitrile, are tolerated in the reaction. An asymmetric (2+2+2) cydoaddition of a,03-diynes with alkyne was achieved by a [IrCl(cod)]2 catalyst combined with a chiral phosphine ligand such as MeDUPHOS and EtDUPHOS, and gave axially chiral aromatic compounds [20]. 

Systematic study on the diastereofacial selectivity in the intramolecular photocycloaddition of alkenes to chiral dioxinones was recently reported by Haddad and coworkers129 on compounds of type 298. Preferred pyramidalization in the direction of the less exposed side (the axial methyl at the acetal center) described in structure 298b, and first bond formation at this position (found to be the case in dioxinones 143 and 146, Scheme 31), are essential features for obtaining selective photocycloadditions of alkenes to chiral dioxinones from this side, leading to the kinetically favored products. In such cases the preferred approach is not necessarily from the more exposed side (Figure 6). 

Successful photoresolution and switching of enantiomers has been accomplished with two types of systems helical overcrowded alkenes and axially chiral cycloalka-nones. 

In 2003, Molander reported the synthesis of (+ )-isoschizandrin using the Sml2-mediated 8-endo-trig carbonyl-alkene cyclisation of ketone 71 (Scheme 7.30).69 The axial chirality of the biaryl system efficiently controls the central chirality of the product. The (Z)-alkene geometry is also vital to the stereochemical outcome and the presence of HMPA in the reaction mixture helps control the conformation of the transition state by increasing the steric demands of the alkoxysamarium substituent.69... 

C. Asymmetric Synthesis of Alkenes with Axial Chirality.314... 

Chiral alkyldihaloboranes are among the most powerful chiral Lewis acids. In general, however, because alkyldihaloboranes readily decompose to alkanes or alkenes as a result of protonolysis or /3-hydride elimination, it is difficult to recover them quantitatively as alkylboronic acids. Aryldichloroborane is relatively more stable and can be reused as the corresponding boronic acid. We have developed chiral aryldichlorobor-anes 23 bearing binaphthyl skeletons with axial chirality as asymmetric catalysts for the Diels-Alder reaction of dienes and a,/3-unsaturated esters (see, e.g., Eq. 37) [36]. 

In our ongoing efforts to develop new and more selective catalysts based on iminium salts, a new family of catalyst was produced, in which the dihydroisoquinolinium moiety has been replaced by a biphenyl structure fused to a sevenmembered azepinium salt [34]. A similar system was developed some years ago by Aggarwal but with axial chirality, achiral at the nitrogen [11] the system gave some good results, although the enantioselectivity of the catalyst was dependent upon the substitution pattern of the alkene. 

An inverse electron demand aza D A reaction of electron rich alkenes with N aryl imines as 2 azadiene (Povarov reaction) provides tetrahydroquinolines. Reactions catalyzed by chiral phosphoric acids yielded different absolute ste reochemical outcomes when ethyl vinyl efher and enecarbamate are employed as electron rich alkenes, although chiral phosphoric acids have the same axial chirality in both cases (see Scheme 3.26). 

This chemistry was extended to a number of bicyclic alkenes and dienes utilizing various chelating axially chiral bisphosphine iridium catalysts (Scheme 11.5) [29]. Further synthetic transformations of the chiral hydroamination product 13 provide access to functionally substituted chiral cyclopentylamines with multiple stereocenters, such as 14 and IS. It should be noted that alkylamines, such as octylamine or N methyl aniline, and sterically encumbered aniline derivatives, such as 0 toluidine or o anisidine did not undergo hydroamination reactions under these conditions. 

Figure 83. Examples of molecules prepared in enantiomerically enriched form using Sharpless KR procedure, (a) Compounds having alternative sites of oxidation acetylene [38], furan [39], and amine [40], (b) Compounds bearing axial chirality [38]. (c) An alkene with planar chirality [41],...

Of the many further examples that could be provided here, one that utilizes the AD reaction to gain access to a series of molecules bearing axial chirality will be discussed [93]. In this case, the trans biaryl alkene shown in Scheme 8.21 was subjected to a highly efficient AD. Cyclization of the diol restricts the motion of the... 

Addition-elimination. Axially chiral l,l -biphenyl-2-carboxylate esters are obtained by the reaction of 2-menthoxybenzoates with aryl Grignard reagents. Conjugate addition followed by elimination of a malonic ester unit constitutes a useful method for the access to (Z)-alkenes. The reagents are 1,1-dimetalloalkanes. 

Metal complexes of enantiomericaUy pure N,N -ethylenebis(salicylideneaminato) (salen) complexes in combination with stoichiometric oxidants currently provide the most selective method for the catalytic asymmetric epoxidation of unfunctionalised alkenes. The use of C2-symmetric salen complexes of manganese(lll) were reported independently in 1990 by Jacobsen and coworkers and Katsuki and coworkers. The first generation catalysts are represented by the general structure (4.33). The complex with R = Bu is known as Jacobsen s catalyst. All of the first generation catalysts are composed of a enantiopure diamine core and possess large substituents at the 3/3 and 5/5 positions. Subsequently Katsuki and coworkers developed second generation catalysts such as (4.34) with axially chiral groups at the 3/3 positions. 

It has been proposed that oxidative addition, rather than alkene association or migratory insertion, is the enantioselective step in the intramolecular Mizoroki-Heck reaction [17]. The snbstrates studied are axially chiral o-iodoanilides 41 with N-Ar rotational barriers that vary from <20 to SOkcalmor depending on the size of (Scheme 12.9) [18]. 

The proposed mechanism is shown in Scheme 12.10. Insertion of the palladium(0) complex into the C—I bond of 42a or 42b with retention of axial chirality gives intermediate 44. This intermediate can still provide either enantiomer of 43, depending on the facial selectivity of migratory insertion. The diastereotopic alkene faces are accessed by rotation... 

The suggestion is then made that the stereoconlrolling step in asymmetric Mizoroki-Heck reactions is oxidative addition (via dynamic kinetic resolution) rather than alkene association or migratory insertion. The implication is that only substrates capable of a dynamic kinetic resolution may cyclize with high enantioselectivity. This would limit the substrate scope of the asymmetric intramolecular Mizoroki-Heck reaction. While the dynamic kinetic resolution during the oxidative addition may be a component of the overall stereoselectivity, it does not rule out contributions from later events in the mechanistic pathway and does not explain the effect of additives on selectivity. What has been shown is that the axial chirality of the o-iodoanilides (as with any enantioenriched isomer of a chiral precursor) influences the stereochemical outcome of their reactions. 

This fundamental experiment has strong implications on related catalyst-controlled Mizoroki-Heck cyclizations of precursors of this type. As axial chirality in 113 sets the stereochemistry in 114, enantioinduction was rationalized to arise from a dynamic kinetic resolution of (at elevated temperature) rapidly interconverting enanhomers of 113 in the oxidative addition step, rather than in the alkene coordination-migratory insertion event. Such a dynamic kinetic resolution process has been previously proposed by Stephenson et al. within their mechanistic study regarding the conformations of helically chiral 2-iodoanilides in intramolecular asymmetric Mizoroki-Heck reactions [72],... 

A catalytic cycle of such an enantiospecific Mizoroki-Heck reaction is outlined in Scheme 7.25. The catalytic cycle starts with an oxidative addition of the C—I bond of (M)-113 to palladium(O), yielding intermediate 115 with retention of axial chirality due to the hindered bond rotation of the N—Ar bond (1 115). Even at this stage, 115 can stiU provide either enantiomer of 114 because the alkene moiety will have to rotate for the insertion into the C(sp )—Pd(II) bond to occur. However, in case of a si-face attack, alkene complexation cannot occur because the palladium... 

As noted earlier in this chapter, the enantioselective hydrosilylation of olefins could be a useful method to prepare chiral, non-racemic alcohols. A.lthough the scope of highly enantioselective hydrosilylations is limited, high enantioselectivities have been obtained for the asymmetric hydrosilylation of alkenes and vinylarenes. A majority of the most selective chemistry has been conducted using a palladium catalyst containing an axially chiral monophosphine ligand. 

Reactions of alkenes and vinylarenes catalyzed by palladium complexes of axially chiral biaryhnonophosphines generate branched products, and these products are formed with high ee. As shown in Equation 16.36, the hydrosilylation of hexene, 4-pheny 1-1-butene, and... 

Efficient asymmetric hydrosilylation of 1-alkenes and selected terminal olefins proceeding in the presence of palladium complexes, such as [ PdCK ) -CsH5) 2], combined with axially chiral monodentate phosphine ligands (MOPs) (Fig. 8) was reported in 1991 by Hayashi and Uozumi (190). [Pd]/MOP systems are highly active and regio- and enantioselective in the asymmetric hydrosilylation of 1-alkenes, terminal olefins (especially styrenes), and cycloolefins with trichlorosilane. Asymmetric hydrosilylation of styrenes occurs successfully in the presence [ PdCl( f-C3H5) 2] combined with MOP (Fig. 8a) (ee up to 94%), modified MOP (Fig. 9) (ee up to 98%), (S)-BINAPO (ee up to 72%), BINASb (Fig. 8b)... 

The control of stereochemistry with chromium carbine complexes has been reviewed. The DBR can create a new stereocenter in three ways. First, the arene tricarbonyl chromium complex contains a plane of chriality, thus the complexes 35 and ent-35 are enantiomers when RL Ri and RS R2. Second, when phenyl substituents are included in the reactants the resulting biaryls can posess axial chirality if there is hindered rotation about the new aryl-aryl bond as in 36. Finally, all DBRs with differentially p-disubstitued alkenes give rise to cyclohexadienones 37 with a new stereocenter adjacent to the carbonyl. When Ri and R2 are not hydrogen, tautomerization cannot occur and the final product possesses a chiral center. 

Table 3. Asymmetric photosensitized cycloaddition reaction of 4 with alkenes using the provisional axial chirality...

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