Substrates cyclic

With cyclic substrates, the formation of the new double bond depends on the availability of a c i -/3-hydrogen, which is required for the yw-elimination... 

The classic method for controlling stereochemistry is to perform reactions on cyclic substrates. A rather lengthy but nonetheless efficient example in the prostaglandin field uses bicyclic structures for this purpose. Bisacetic acid derivative S is available in five steps from Diels-Alder reaction of trans-piperylene and maleic anhydride followed by side-chain homologation. Bromolactonization locks the molecule as bicyclic intermediate Esterification, reductive dehalogen-... 

Conjugated dienes can be epoxidized to provide vinylepoxides. Cyclic substrates react with Katsuki s catalyst to give vinylepoxides with high ees and moderate yields [17], whereas Jacobsen s catalyst gives good yields but moderate enantiose-lectivities [18]. Acyclic substrates were found to isomerize upon epoxidation (Z, )-conjugated dienes reacted selectively at the (Z)-alkene to give trans-vinylepoxides (Scheme 9.4a) [19]. This feature was utilized in the formal synthesis of leuko-triene A4 methyl ester (Scheme 9.4b) [19]. 

This reagent reacts with a,/3-unsaturated ketones to give kinetic products of exclusive 1,4-addition (2). With cyclic substrates, a strong preference for axial addition is observed, as is a susceptibility to steric hindrance. Transformation into the corresponding silylcuprate species permits conjugate addition to a wider variety of a,/3-unsaturated substrates (3,4). 

In anti addition to a cyclic substrate, the initial attack by the electrophile is also from the less-hindered face. However, many (though not all) electrophilic additions to norbomene and similar strained bicycloalkenes are syn additions." In these cases attack is always from the exo side, for example," ... 

In addition to the cyclic substrates described above, several open-chain compounds are known to undergo heterolytic cleavage of a carbon-carbon tr bond. 

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... 

The reaction also tolerated the thiol group on the cyclic substrate butylthio-cyclooctene 37 was ring-opened in the presence of an excess of ethene to give a good yield of the diene 38 (Eq. 30). 

Use of a symmetrical acyclic alkene limits the possible metathesis products to the desired diene (for example 45) and products formed from polymerisation of the cyclic substrate. Competing ROMP was suppressed in these reactions by using dilute conditions and a tenfold excess of hex-3-ene. By adding the cyclic substrate slowly to a solution of the catalyst and ris-hex-3-ene (which was significantly more reactive than the trans isomer), less than two equivalents of the acyclic alkene were used without causing a significant drop in the cross-metathesis yield. 

Good levels of regioselectivity were observed, however, when analogous cyclic substrates containing a hydroxy (51) or methyl substituent (52) projecting from the exo-face of the cyclobutene were used. Formation of exclusively tram double bonds in the major regioisomers was also observed with these substrates (Eq. 37) (Table 4). 

Other functional groups which have a heteroatom rather than a hydroxyl group capable of directing the hydrogenation include alkoxyl, alkoxycarbonyl, carboxylate, amide, carbamate, and sulfoxide. The alkoxy unit efficiently coordinates to cationic iridium or rhodium complexes, and high diastereoselectivity is induced in the reactions of cyclic substrates (Table 21.3, entries 11-13) [25, 28]. An acetal affords much lower selectivity than the corresponding unsaturated ketone (Table 21.3, entries 14 and 15) [25]. 

Complex 24 a proved to be a particularly efficient catalyst for the hydrogenation of the cyclic substrate 5, affording 95% ee, which currently is the highest ee-value obtained with any catalyst for this substrate. High enantioselectivities were also obtained with a,/ -unsaturated substrate 6. Catalyst 24 a also gave higher selectivity than the ThrePHOX catalysts 23 in the hydrogenation of substrates 2 and 4. 

Woodward s achievement in constructing the 10 chiral centers of lb relied on the cyclic substrate control approach. Erythromycin A (la) was finally synthesized by combining compound lb with a long chain residue. Although this achievement represented a historic milestone at that time, it also attested to the limitations of this popular traditional approach. 

Approach (control) Acyclic (reagent) Cyclic (substrate) Acyclic (substrate) Acyclic (reagent) Acyclic... 

The numerous studies prior to 1996 on Cu-catalyzed additions of Grignard reagents to cydohexenone as a model substrate revealed that, with a few exceptions, enantioselectivity was exclusively found with either cyclic substrates (Grignard reagents) or acyclic substrates (dialkylzinc reagents) (Scheme 7.2). 

Aryldichlorotellurolactones (general procedure). A solution of the 7,5-unsaturated acid (5 mmol) and/7-methoxyphenyltellurium trichloride (2.0 g, 5.8 mmol) in CHCI3 (80 ml.) is heated under reflux (acyclic substrates, 1 h cyclic substrates, 2.5-7 h). The solution is evaporated and the residue filtered through SiOj with the aid of CHCI3. The solution is dried (MgS04) and evaporated. The residue is recrystallized from CHCl3/petroleum ether at 30-60°C, giving the pure product. 

Note that with some cyclic substrates, the leaving group may remain as part of the product alkene. Elimination reactions played an important role in... 

Medium sized carbocycle synthesis Ring contracting [1,2]-Wittig rearrangement Yadav and Ravishankar have demonstrated that the Wittig rearrangement of the cyclic substrate 32 is useful for the construction of the taxane skeleton 33, albeit in low yield (equation 17). ... 

A rule, similar to Prelog s rule, has been proposed for the enzyme-mediated hydrolysis of the esters of secondary alcohols. Esters of the enantiomers 31 usually react faster. This rule correctly predicted the configuration of 14 out of 15 substrates when cholesterol esterase was used, 63 out of 64 substrates with a lipase from Pseudomonas cepacia, and of 51 out of 55 cyclic substrates using a lipase from Candida rugosa24°. 

For a distinction in the binding mode of substrate constitutional isomers, we first focused on the synthesis of the structurally related anhydroalditol derivatives 7 and 8 as potential inhibitors of FucA that lack the anomeric hydroxyl group of the natural substrate 5 and thus ehminate the possibility for ring opening and cleavage [12] (Scheme 2.2.5.3). Fucitol 1-phosphate 10 was included in the study as a potential mimic of the open-chain form. From kinetic data it became obvious that the aldolase binds preferentially a cyclic substrate, and selectively the more abundant P-anomer of the natural substrate that correlates with 7. 

Cyclic substrates. Cyclopropyl substrates are extremely resistant to nucleophilic attack.285 For example, cyclopropyl tosylate solvolyzes about 106 times more slowly than cyclobutyl tosylate in acetic acid at (WC.286 When such attack does take place, the result is generally not normal substitution (though exceptions are known,287 especially when an a stabilizing group such as aryl or alkoxy is present) but ring opening 288... 

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