A stereocontrolled synthesis

More functionalized 5,6-dihydro-2H-pyran-derivatives 71 and 72 have been prepared [26] by cycloaddition of 1 -methoxy-3-trialkylsilyloxy-1,3-butadienes 69 with t-butylglyoxylate (70) (Scheme 5.6). Whereas thermal reactions did not occur in good yields because of the decomposition of the cycloadducts, application of pressure (10 kbar) allowed milder conditions to be used, which markedly improved the reaction yields. The use of high pressure also gives preferentially en Jo-adduct allowing a stereocontrolled synthesis of a variety of substituted 5,6-dihydro-2H-pyran-derivatives, which are difficult to prepare by other procedures. 

In considering the retrosynthetic analysis of juvabione, two factors draw special attention to the bond between C(4) and C(7). First, this bond establishes the stereochemistry of the molecule. The C(4) and C(7) carbons are stereogenic centers and their relative configuration determines the diastereomeric structure. In a stereocontrolled synthesis, it is necessary to establish the desired stereochemistry at C(4) and C(7). The C(4)-C(7) bond also connects the side chain to the cyclohexene ring. As a cyclohexane derivative is a logical candidate for one key intermediate, the C(4)-C(7) bond is a potential bond disconnection. 

The rearrangement provides a stereocontrolled synthesis of the C-pyranoside 2, present in pseudomonic acids.2... 

Perhaloalkanes have been found to scramble halogen atoms via consecutive halophilic reactions following carbanion generation by halophilic attack by base. S l reaction of an allylsilane has been applied in a stereocontrolled synthesis of ( )-dihydronepetalactone, and functionalized aryl and arylmethyl carbanions have been generated by reductive cleavage of aryl and arylmethyl alkyl ethers by electron transfer from alkali metals. ... 

A stereocontrolled synthesis of racemic monomorine I (16a) has been accomplished by Stevens and Lee (438). An allyl alcohol obtained by reaction of acrolein with the Grignard reagent of the chloroacetal (367) was oxidized to yield the enone (368). The Michael addition of 1-nitropentane to 368 was catalyzed by tetramethylguanidine to yield the nitroalkane (369). Reductive cyclization of 369... 

Pedamide 536 was converted by treatment with trimethyloxonium tetrafluoro-borate to methyl pedimidate (549) (475), which was connected by the reaction sequence shown in Scheme 69 to (-l-)-acetylpederic acid (550), prepared via a route similar to that to the racemic pederamide (536) from (—)-(2/ ,3/ )-2,3-butanediol. The ratio of the resulting (-l-)-pederin (147) to (+)-10-epipederin (551) was 1 3. This ratio can be inverted to 60 14 by a stereocontrolled synthesis (476) including connection of methyl pedimidate (549) and (+)-selenoacid (552)... 

A. Spaltenstein, P.A. Carpino, F. Miyake, P.B. Hopkins, A stereocontrolled synthesis of frans-alkene isosteres of dipeptides. Tetrahedron Lett. 27 (1986) 2095-2098. 

Steroid side chain. Two laboratories- 4 have reported a stereocontrolled synthesis of the steroid chain with the natural conliguration at C. by the catalyzed... 

Antkracyclinones. A key step in a stereocontrolled synthesis of 4-demethoxy-daunomycinone (4) involves cycloaddition of the epoxide 1 with this diene (2). Later steps follow known transformations. 

This insertion reaction has provided a stereocontrolled synthesis of ( + > thienamycin (3), an important carbapenem antibiotic.5... 

The stereochemistry at C7 was introduced by the hydrogenation of the ketone. Although this hydrogenation was very selective for the desired stereoisomer, the process provided no information to confirm or refute the tentative stereochemical assignment at this center, which remained incorrectly assigned until Weinreb completed a stereocontrolled synthesis of 7-epicylindrospermopsin in 2001.7a... 

A stereocontrolled synthesis of Z-vancosamine (72) was achieved by Nicolaou and co-workers starting from 168 via IBX-induced cyclization followed by CAN-mediated removal of PMB group and basic hydrolysis [130] (Scheme 38). 

A stereocontrolled synthesis of 2,4,5-trisubstituted tetrahydropyrans 331 can be achieved via a Lewis-acid-catalyzed intramolecular Prins cyclization of homoallylic acetals 332. Incorporation of a variety of substituents at C-4 of the resulting tetrahydropyrans is possible by simple variation of the reaction conditions (Equation 141, Table 13) <2001CC835>. 

A stereocontrolled synthesis of the biologically active neolignan (+)-dehydrodiconiferyl alcohol, which was isolated from several Taxus species, was achieved via Evans asymmetric aldol condensation [58] using ferulic acid amide derived from D-phenylalanine. The reaction steps are shown in Fig. 9. This stereocontrolled reaction is also useful for preparing the enantiomer of (+)-dehydroconiferyl alcohol using chiral auxiliary oxazolidinone prepared from L-phenylalanine. This reaction also enables the syntheses of other natural products that possess the same phenylcoumaran framework. 

Conjugate addition.s The key step in a stereocontrolled synthesis of the Lyth-raceae alkaloid lasubine II (4) is the conjugate addition of an alkylcopper complexed with BF3 to the N-acyl-2,3-dihydro-4-pyridone 1 to give the d.v-product 2 in 56% yield and >96% stereoselectivity. Hydrogenation in the presence of Li2C03 effects cyclization and deprotection of nitrogen to give the ketone 3, which is reduced stereoselectively by lithium trisiamylborohydride to the desired alcohol 4. 

Demethyldeoxynupharidine (5) was synthesized from (—)-castoramine (59) in six steps (Scheme 6) (26). Syntheses of ( )-nupharolutine (50) and of ( )-7-epinupharolutine (60) were completed from cyclopentanone derivative 61 (Scheme 7) (62). A stereocontrolled synthesis of ( )-anhydronupharamine (62) was achieved in six steps from cyclopentanone derivative 63 (Scheme 8) (63). Tufariello (64) pointed out the possibility of synthesizing of 7-demethylodeoxy-nupharidine (5) from nonfunctionalized nitrones such as 64 (Scheme 9). Compound 65, after cyclization and removal of the ketone group, would furnish a synthesis of alkaloid 5. 

A stereocontrolled synthesis of racemic anhydronupharamine (30) has been described (Scheme 4),25 and its and 13C n.m.r. spectra have been measured.25,26... 

A stereocontrolled synthesis of the /ra j-tetrahydrofuran units in Annonaceae acetogenins that relies on the Sharpless asymmetric dihydroxylation protocol is outlined in Scheme 60 <1999TA2551>. In the first step, the disubstituted double bond of the starting material is dihydroxylated followed by monoprotection as a methoxymethyl ether. Einally, a cobalt-catalyzed oxidation using molecular oxygen as oxidant furnishes the /ra j-tetrahydrofuran. 

These iron complexes can be used to effect a stereocontrolled synthesis of 4,4,5-trisubstituted cyclohexenones. An example is shown in equation (I). 

This addition to a pyranosyl heteroalkene provided an important diastereoselective step in a stereocontrolled synthesis of maytansinol, a 19-membered lactam with seven asymmetric centers.3... 

The catalytic effect of boron triacetate was used in a stereocontrolled synthesis of altersolanol B (6). ... 

A stereocontrolled synthesis of the vitamin E side chain alcohol was achieved in an elegant fashion (equation 121) allowing mutation from a 1,4- to a 1,5-acyclic stereoselection process applicable also to the optically active series . 

Beau, J M, Sinay, P, D-Glycopyranosyl phenyl sulfones their use in a stereocontrolled synthesis of cA-2,6-disubstituted tetrahydropyrans ((3-D-C-glycosides), Tetrahedron Lett., 26, 6189-6192, 1985. Schmidt, R R, Preuss, R, Betz, R, Vinyl carbanions. 33. C-1 lithiation of C-2 activated glucals. Tetrahedron Lett., 28, 6591-6594, 1987. 

A stereocontrolled synthesis of polyfused ring systems utilizing the chloroacetoxylation approach is shown in Scheme 8-26 [95]. Sequential ally lie substitution of the chloroacetates afforded key intermediate 75. Subsequent palladium-catalyzed tandem metalloene/Heck insertion reactions gave polyfused ring systems 76 and 77. 

J.K. Cha et al. developed a stereocontrolled synthesis of bicyclo[5.3.0]decan-3-ones from readily available acyclic substrates. Acyclic olefin-tethered amides were first subjected to the intramolecular Kulinkovich reaction to prepare bicyclic aminocyclopropanes. This was followed by a tandem ring-expansion-cyclization sequence triggered by aerobic oxidation. The reactive intermediates in this tandem process were aminium radicals (radical cations). The p-anisidine group was chosen to lower the amine oxidation potential. This substituent was crucial for the generation of the aminium radical (if Ar = phenyl, the ring aerobic oxidation is not feasible). 

Paquette, L. A, Stereocontrolled synthesis of complex cyclic ketones by oxy-Cope rearrangement. Angew. Chem. 1990, 102, 642-660. 

Kozikowski, A.P., and Sorgi, K.L., Use of the anomeric allylation reaction in natural products synthesis. A stereocontrolled synthesis of methyl deoxypseudomonate B, Tetrahedron Lett., 25, 2085, 1984. Hammond, G.B., Cox, M.B., and Wiemer, D.F., Stereocontrol in Homer-Wadsworth-Emmons condensations of a gezw-dimethylcyclopropyl aldehyde with a-substituted phosphono acetates, J. Org. Chem., 55, 128, 1990. 

A stereocontrolled synthesis of the side-chain acid 186 of isoharringtonine from (R,R)-(-l-)-tartaric acid was reported by Zhang etal. (63) (Scheme 30). Dimethyl (2R, 3i )-tartrate acetonide (182) was allylated in the presence of lithium diisopropylamide to give 183, which underwent base-catalyzed epimerization to 184. Catalytic hydrogenation, followed by hydrolysis and by treatment with methanol in the presence of sulfuric acid, yielded the half ester 185, which was treated with aqueous trifluoroacetic acid to provide the side-chain acid of isoharringtonine (186) with the appropriate stereochemistry. 

Diazo reagents have also been utilized in the preparation of pyrazoles. 1,3-Dipolar cycloaddition of 2-diazopropane with propargyl alcohols led to the regioselective synthesis of 3//-pyrazoles <05EJO3526>. Reactions of diazomethane or diazoethane with activated sulfoxides 47 in the presence of Yb(OTf)3 produced a stereocontrolled synthesis of bicyclic pyrazoles 48 <05JOC8942>. 

---