Olefins stereocontrol

Scheme 16. Mo-catalyzed tandem AROM/CM proceeds with high enantioselectivity and olefin stereocontrol...

A conceptually interesting approach to the synthesis of CJH involves the reaction of allyUc substrates of type 108 with methyl carbanion equivalents in an 8 2 manner. Several syntheses have followed this approach. The Still-Collum-Mitra synthesis used enforced 8 2 methodology, a 2,3-sigmatropic rearrangement of allylic alcohols (108 where X=OH). The big questions in this approach were (1) what would be used as a CH3" equivalent and (2) would the desired olefin stereocontrol be achieved ... 

Supression of olefin isomerization is critical for acyclic stereocontrol ... 

The completion of the synthesis of the polyol glycoside subunit 7 requires construction of the fully substituted stereocenter at C-10 and a stereocontrolled dihydroxylation of the C3-C4 geminally-disub-stituted olefin (see Scheme 10). The action of methyllithium on Af-methoxy-Af-methylamide 50) furnishes a methyl ketone which is subsequently converted into intermediate 10 through oxidative removal of the /j-methoxybenzyl protecting group with DDQ. Intermediate 10 is produced in an overall yield of 83 % from 50) , and is a suitable substrate for an a-chelation-controlled carbonyl addition reaction.18 When intermediate 10 is exposed to three equivalents of... 

Ferrocen-l,l -diylbismetallacycles are conceptually attractive for the development of bimetal-catalyzed processes for one particular reason the distance between the reactive centers in a coordinated electrophile and a coordinated nucleophile is self-adjustable for specific tasks, because the activation energy for Cp ligand rotation is very low. In 2008, Peters and Jautze reported the application of the bis-palladacycle complex 56a to the enantioselective conjugate addition of a-cyanoacetates to enones (Fig. 31) [74—76] based on the idea that a soft bimetallic complex capable of simultaneously activating both Michael donor and acceptor would not only lead to superior catalytic activity, but also to an enhanced level of stereocontrol due to a highly organized transition state [77]. An a-cyanoacetate should be activated by enolization promoted by coordination of the nitrile moiety to one Pd(II)-center, while the enone should be activated as an electrophile by coordination of the olefinic double bond to the carbophilic Lewis acid [78],... 

Similar catalytic reactions allowed stereocontrol at either of the olefin carbons (Scheme 5-13, Eqs. 2 and 3). As in related catalysis with achiral diphosphine ligands (Scheme 5-7), these reactions proceeded more quickly for smaller phosphine substrates. These processes are not yet synthetically useful, since the enantiomeric excesses (ee s) were low (0-27%) and selectivity for the illustrated phosphine products ranged from 60 to 100%. However, this work demonstrated that asymmetric hydrophosphination can produce non-racemic chiral phosphines [13]. 

The synthesis in Scheme 13.21 starts with a lactone that is available in enantiomer-ically pure form. It was first subjected to an enolate alkylation that was stereocontrolled by the convex shape of the cis ring junction (Step A). A stereospecific Pd-mediated allylic substitution followed by LiAlH4 reduction generated the first key intermediate (Step B). This compound was oxidized with NaI04, converted to the methyl ester, and subjected to a base-catalyzed conjugation. After oxidation of the primary alcohol to an aldehyde, a Wittig-Horner olefination completed the side chain. 

The chain-end stereocontrol for olefin polymerizations leads generally to lower stereoselectivities (differences in activation energy for insertion of the two enantiofaces generally lower than 2 kcal/mol) than the chiral site stereo-control.18131132 For this reason, the corresponding catalytic systems have not reached industrial relevance for propene homopolymerization. However, some of them are widely used for propene copolymerization with ethene. 

The mechanisms of stereoselectivity which have been proposed for chain-end stereocontrolled polymerizations involving secondary monomer insertion also present a general pattern of similarity. In fact, molecular modeling studies suggest that for olefin polymerizations (both syndiospecific and isospecific, Section 4.1.2) as well as for styrene polymerization (syndiospecific, Section 4.2), the chirality of the growing chain would determine the chirality of a fluxional site, which in turn would discriminates between the two monomer enantiofaces. 

As depicted in Scheme 21, subjection of 86 with 20 mol% of freshly prepared 2 after 4 h at 22 °C indeed afforded 87 in 92% yield after silica gel chromatography (>98% Z). Stereocontrolled hydrogenation of the trisubstituted olefin (72% yield) and removal of the acetate and trifluroacetate groups, effected by subjection of the hydrogenated adduct with hydrazine in MeOH, delivered Sch 38516 (1) in 96% yield to complete the total synthesis. 

Typical electrophiles that attack olefins like Br+ (Eq. 64)105) and (OH)+ (Eq. 65) 105) do lead to electrophilic addition with ring enlargement101 a). Most interesting is the ability for electrophiles that normally do not attack olefins to also react. Thus, an oxycarbonium ion generated from an acetal smoothly alkylates the double bond of this composite functional group in an overall highly stereocontrolled 1,1,2-trialkylation of a simple ketone as illustrated in Eq. 66 106). The chemo- and... 

The opening of cyclopropylcarbinols to homoallylic bromides constituted the first use of cyclopropyl compounds for the stereocontrolled synthesis of natural products. The cyclopropyl conjunctive reagents enhance the richness of this notion. The stereocontrolled opening of vinylcyclopropanes by a homopentadienyl proton shift provides an approach to trisubstituted olefins and thereby a new strategy. The fungal prohormone methyl trisporate B (224) as summarized in Scheme 15 illustrates this conceptual development97). 

Tricyclohexaprenol, a possible forerunner of sterols in the evolution of biomembranes, was synthesized by construction of the cyclic network in one step using cation-olefin tricyclization and subsequent stereocontrolled attachment of the Ci0 appendage to ring C. 

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