Enantioselective synthesis double

The target molecule above contains a chiral center. An enantioselective synthesis can therefore be developed We use this opportunity to summarize our knowledge of enantioselective reactions. They are either alkylations of carbanions or addition reactions to C = C or C = 0 double bonds ... 

For the performance of an enantioselective synthesis, it is of advantage when an asymmetric catalyst can be employed instead of a chiral reagent or auxiliary in stoichiometric amounts. The valuable enantiomerically pure substance is then required in small amounts only. For the Fleck reaction, catalytically active asymmetric substances have been developed. An illustrative example is the synthesis of the tricyclic compound 17, which represents a versatile synthetic intermediate for the synthesis of diterpenes. Instead of an aryl halide, a trifluoromethanesul-fonic acid arylester (ArOTf) 16 is used as the starting material. With the use of the / -enantiomer of 2,2 -Z7w-(diphenylphosphino)-l,F-binaphthyl ((R)-BINAP) as catalyst, the Heck reaction becomes regio- and face-selective. The reaction occurs preferentially at the trisubstituted double bond b, leading to the tricyclic product 17 with 95% ee. °... 

An (E)-selective CM reaction with an acrylate (Scheme 61) was applied by Smith and O Doherty in the enantioselective synthesis of three natural products with cyclooxygenase inhibitory activity (cryptocarya triacetate (312), cryptocaryolone (313), and cryptocaryolone diacetate (314)) [142]. CM reaction of homoallylic alcohol 309 with ethyl acrylate mediated by catalyst C led (E)-selectively to d-hydroxy enoate 310 in near quantitative yield. Subsequent Evans acetal-forming reaction of 310, which required the trans double bond in 310 to prevent lactonization, led to key intermediate 311 that was converted to 312-314. 

The same authors also used this approach for an enantioselective synthesis of the natural product (-i-)-royleanone (4-54), a member of the abietane diterpenoid family [17]. The enantiopure sulfoxide 4-50 was oxidized using DDQ to give crude 1,4-ben-zoquinone 4-51, which by reaction with the diene 4-52 in CH2C12 under high pressure led to the tricyclic compound 4-53 with 97 % ee and 60% yield based on 4-50 (Scheme 4.11). Hydrogenation of the unconjugated double bond in 4-53 afforded 35% of the desired compound 4-54 after crystallization to separate it from the unwanted cis-isomer. 

A wide variety of iridium-based hydrogenation catalysts are currently under development, notably for organic syntheses including enantioselective synthesis. Hydrogenation by hydrogen transfer is well known [15], and the reduction of C=0 and C=N double bonds is also possible [16, 17]. 

Many methods have been reported for the enantioselective synthesis of the remaining PG building block, the (J )-4-hydroxy-cyclopent-2-enone. For example, the racemate can be kinetically resolved as shown in Scheme 7-28. (iS )-BINAP-Ru(II) dicarboxylate complex 93 is an excellent catalyst for the enantioselective kinetic resolution of the racemic hydroxy enone (an allylic alcohol). By controlling the reaction conditions, the C C double bond in one enantiomer, the (S )-isomer, will be prone to hydrogenation, leaving the slow reacting enantiomer intact and thus accomplishing the kinetic resolution.20... 

The main lines of this approach were later embodied in an enantioselective synthesis of (—)-a-allokainic acid (Scheme 34) (179). The sole stereo center of die ene reaction starting material was derived from a glutamic acid derivative (132) to avoid loss of optical activity via double bond migration (see Scheme 33), the a acid function of kainic acid had to be reduced before the pyrolysis step... 

The cyclopropane aldehyde 156 was identified as a versatile chiral building block for the enantioselective synthesis of 4,5 disubstituted y-butyrolactones of type 158 or 159. Both enantiomers of 156 can be easily obtained in a highly diastereo- and enantioselective manner from fixran-2-carboxylic ester 154 using an asymmetric copper-catalyzed cyclopropanation as the key step followed by an ozonolysis of the remaining double bond (Scheme 25) [63]. Addition of... 

Ammonia lyases catalyze the enantioselective addition of ammonia to an activated double bond. A one-pot, three-step protocol was developed for the enantioselective synthesis of L-arylalanines 50 using phenylalanine ammonia lyase (PAL) in the key step (Scheme 2.20). After formation of the unsaturated esters 48 in situ via a Wittig reaction from the corresponding aldehydes, addition of porcine Ever esterase and basification of the reaction mixture resulted in hydrolysis to the carboxylic acids 49. Once this reaction had gone to completion, introduction of PAL and further addition of ammonia generated the amino acids 50 in good yield and excellent optical purity [22]. 

Allyltriorganosilanes react with activated C-N double bonds such as iminium salts and Lewis acid-coordinated imines at the y-position to give homoallylamines.14,118 For example, in the presence of BF3, iV-acylimines generated in situ by the reaction of aldehydes or acetals with carbamates are efficiently allylated with allyltrimethylsilanes (Equation (26)).119,119a,12° The use of homochiral crotylsilanes such as 20 leads to highly diastereo- and enantioselective synthesis of homoallylamines (Equation (27)). a Allenylation of the iV-acylimines can be performed with propargylsi lanes. 

The enantioselective synthesis of (-)-sedacryptine, a piperidine alkaloid, has been achieved via the double intramolecular conjugate addition of a carbamate group onto a vinyl sulfone and then an enone (Scheme 30). The first conjugate addition of 108 proceeded in a. syn-1,3 fashion. The successive cyclization of the resulting carbamate anion 110, which was formed from carbanion 109 via proton transfer, gave a mixture of stereoisomeric products 111 and 112. Both of these isomers were converted into the target natural product.76... 

The development of this so far unprecedented, double Brpnsted acid catalyzed enantioselective synthesis of various aromatic and heteroaro-... 

The enantioselective synthesis of optically active secondary amines via asymmetric reduction of prochiral ketimines was studied by screening various chiral hydrides. In this case, K-glucoride gave only disappointing results and was inferior to other reagents. Better results were obtained in the asymmetric reduction of prochiral Af-diphenylphosphinylimines to chiral N-(diphenylphosphinyl)amines (eq 1), which can then be readily converted into optically active primary amines. For this reaction the stereochemical course depends dramatically on the relative bulkiness of the groups R and R. The reaction conditions for reduction of C=N double bonds are the same as used for ketones, but the high reactivity of diphenylphosphinylimines dramatically reduces the reaction time. 

He L, Byun H-S, Smit J, Wilschut J, Bittman RJ. Enantioselective synthesis of a novel trans double bond ceramide analogue via catalytic asymmetric dihydroxylation of an enyne. The role of the trans double bond of ceramide in the fusion of Semliki Forest virus with target membranes. J. Am. Chem. Soc. 1999 121 3897-3903. Broun P, Shanklin J, Whittle E, Somerville C. Catalyic plasticity of fatty acid modification enzymes underlying chemical diversity of plant lipids. Science 1998 282 1315-1317. 

We have found that chiral boronate complexes with BLA (Brpnsted acid-assisted chiral Lewis acids) to give new catalysts for enantioselective synthesis which achieve selectivity by a double effect of intramolecular hydrogen-bonding interaction and attractive ji-ti donor-acceptor interaction in the transition state by a hydroxy aromatic group [27a],... 

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