Enantioselective Wittig reaction

An enantioselective Wittig reaction was accomplished by the solid-state reaction of a 1 1 complex of 10b and 122 or 10c and 143 with 141, which gives... 

An enantioselective Wittig reaction was accomplished by the crystal-crystal reaction of a 1 1 complex of 4 b and 13 a or 13 b with 14, which gives the corresponding (-)-olefm 15 a of 42% ee (73%) or 15 b of 73% ee (73%), respectively, in the yield indicated [12], An enantioselective Michael addition reaction was also achieved in an inclusion complex with a chiral host compound. Treatment of a 1 1 complex of 4 c and 16 with 2-mercaptopyridine 17 in the solid state gave (—)-18 of 80% ee in 51% yield [13]. 

Krauueer, M., Hummel, W. and Groeger, H. (2007) Enantioselective one-pot two-step synthesis of hydrophobic allylic alcohols in aqueous medium through the combination of a Wittig reaction and an enzymatic ketone reduction. European Journal of Organic Chemistry, (31), 5175—5179. 

Subsequent monosilylation and Wittig reaction furnished unsymmetrical double diene 170. The synthesis of the other Diels-Alder partner started from bromophenol 173 (prepared in three steps from dimethoxytoluene), which was doubly metalated and reacted with (S,S)-menthylp-toluenesulfinate 173. CAN oxidation delivered quinone 171, which underwent a Diels-Alder reaction with double diene 170 to give compound 175 possessing the correct regio- and stereochemistry. Upon heating in toluene the desired elimination occurred followed by IMDA reaction to adduct 176, which was obtained in an excellent yield and enantioselectivity. Both Diels-Alder reactions proceeded through an endo transition state the enantioselectivity of the first cyclization is due to the chiral auxiliary, which favors an endo approach of 170 to the sterically less congested face (top face) (Scheme 27). 

Alternatively, enzymatic resolution of 61 by hydrolysis or of 62 by enzymatic esterification could be achieved with >99% ee and enantioselectivities of E>200, e.g. hydrolysis with common lipases like CAL-B or BCL (Amano PS) [86-88]. Wittig reaction and deprotection led to 64. Enzymatic resolution is also possible at the stage of C15-racemic 65 [86-88]. 

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]. 

Enantioselective Intramolecular Wittig Reaction. Asymmetric induction has been reported to accompany intramolecular Wittig cyclization of a phosphonium ylide performed in the presence of (/J,5)-CAMPHOS catalyst. However, this reaction proceeds to afford the corresponding cyclization product with only 10% ee (eq 4) ... 

Only three enantioselective Wittig-Homer reactions using optically active reagents have been reported [17J. In comparison with these, the solid state reaction is much more simple and successful. 

An attempted enantioselective synthesis of ipalbidine from the protected (S)-prolinol 860 was based on the regioselective 6-exo-trig cyclization of the radical intermediate derived from the reaction of the phenylthio compound 861 with tributyltin hydride (Scheme 111) (577). The reaction gave a 1 1 mixture of two indolizidin-5-one diastereomers 862 in 65% yield. At the end of the synthesis, the target 842 was found to possess virtually no optical activity. The most likely candidate for racemization is the aldehyde 863, which might scramble under the basic conditions required for the subsequent Wittig reaction. 

When solid-solid reactions are carried out in an inclusion crystal with a chiral host, the reactions can be monitored to proceed enantioselectively. As a typical example, the Wittig reaction according to Eq. (44) was studied as a 1 1 inclusion crystal of ketone and a chiral diol as host [76]. 

The Wittig reaction has been used to construct the side-chain in a synthesis of (-)-sirenin (208), a water mold sperm-attacking hormone.ii The intermediate (206) was generated, without competing formation of the structural isomer (207), by reaction of the ylide (205) with (204) under salt-free conditions in DME. Standard Wittig methods have been used to construct the side-chain in an enantioselective synthesis of (+)-(7 , 9Z)-methyl trisporate (209) and its (9E)-isomer.l 12 The reaction of triphenyl-(vinylimino)phosphorane derivatives (210) with tropones provides a convenient synthesis of 1-aza-azulenes (211) and (212) in either one or two steps (Scheme 28).H The mechanism of the one-step reaction was investigated using deuterium-labelled tropane derivatives. 

Zhu and Panek s total synthesis [148] is described in Scheme 89. After conversion of aldehyde 609 to di-benzyl acetal, treatment with chiral crotylsilane 610 afforded l,2-5y -611 with high stereo- and enantioselectivity. The oxidative cleavage of the double bond and subsequent aldol reaction with silyl ketene acetal 612 provided 613, which was converted into a,P-unsaturated ester 614 via Wittig olelination. The C8 methyl group was stereoselectively introduced by treatment with dimethylcuprate in the presence of TMSCl. DIB AH treatment differentially reduced the C3 and CIO esters to alcohol and aldehyde, respectively. Protection of the alcohol as silyl ether followed by the Wittig reaction afforded 615. In a manner similar to Danishefsky s synthesis [142d], an inteimolecular Suzuki... 

The enantioselective Wittig and epoxide rearrangements have been widely explored in the last few years. They are of interest since such processes can, in a single step, induce asymmetry and molecular complexity that would be difficult to generate otherwise. Advances in substrate scope, reaction efficiency and catalytic process constitute significant challenges for the future. 

Several other stereoselective transformations have been presented that afford ehiral eyelohexenones, ° ° cyclohexadienones, or cyclopenta-nones. °° For instanee, tandem Michael addition/Wittig reaction of (3-carbo q -2-oxopropylidene) triphenylphosphorane and a,p-unsaturated aldehydes has been developed by employing catalysis by newly designed bullq chiral secondary amine C10. ° The multifunctional 6-carbo3gr-cyclohex-2-en-l-ones were generally obtained in excellent diastereo- and enantioselectivities (Seheme 8.23). 

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