Naturally occurring reaction scheme

The Pd-catalyzed coupling reactions of alkenyl bromides with heterocyclic alkynes (40) under the above phase-transfer conditions have been employed to prepare a large number of heterocyclic alkyne derivatives, including some naturally occurring compounds (Scheme 28). The experiment conditions... 

The high enantioselectivity of the exo product opens up a new and readily accessible route to an enantioselective synthesis of interesting isoquinoline alkaloids (Scheme 6.15) [35]. The tricyclic isoxazolidine exo-15b was obtained from the 1,3-dipolar cydoaddition reaction as the pure exo isomer and with 58% ee [34]. As shown in Scheme 6.15 the exo product from the 1,3-dipolar cydoaddition was converted into 17 in two steps without racemization at the chiral center. In addition to the illustrated synthesis, the 6,7-dimethoxy-derived isoxazolidine exo-15b is a very useful precursor for the synthesis of naturally occurring isoquinoline alkaloids [36-40]. 

Wang recently reported [30] that thermolysis of carbodiimides 15 (Scheme 1.5) in aromatic solvents is an efficient route to indoloquinolines 18 used as precursors for synthesizing naturally occurring alkaloids [31], The cyclization is thought to occur through a two-step biradical Diels-Alder reaction that gives 17, which then tautomerizes to 18. 

The synthesis of chaparrinone and other quassinoids (naturally occurring substances with antileukemic activity) is another striking example [16a-c]. The key step of synthesis was the Diels-Alder reaction between the a,/l-unsaturated ketoaldehyde 1 (Scheme 6.1) with ethyl 4-methyl-3,5-hexadienoate 2 (R = Et). In benzene, the exo adduct is prevalent but it does not have the desired stereochemistry at C-14. In water, the reaction rate nearly doubles and both the reaction yield and the endo adduct increase considerably. By using the diene acid 2 (R = H) the reaction in water is 10 times faster than in organic solvent and the diastereoselectivity and the yield are satisfactory. The best result was obtained with diene sodium carboxylate 2 (R = Na) when the reaction is conducted 2m in diene the reaction is complete in 5h and the endo adduct is 75% of the diaster-eoisomeric reaction mixture. 

Benzoxazine, an heterocycle present as structural subunit in many naturally occurring and synthetic bioactive compounds, was prepared under microwave irradiation from a mixture of 2-aminophenol 218 and an a-bromoester 219 (Scheme 80). The reaction proceeded through an initial base-catalyzed alkylation of the phenoUc OH followed by spontaneous amidation. Yields from 44 to 78% were reported for 17 different benzoxazines 220 [ 141]. 

Organosilicon compounds are widely used in our daily life as oil, grease, rubbers, cosmetics, medicinal chemicals, etc. However, these compounds are not naturally occurring substances but artificially produced ones (for reviews of organosilicon chemistry, see [59-64]). Hydrosilylation reactions catalyzed by a transition-metal catalyst are one of the most powerful tools for the synthesis of organosilicon compounds. Reaction of an unsaturated C-C bond such as alkynes or alkenes with hydrosilane affords a vinyl- or alkylsilane, respectively (Scheme 16). 

The direct preparation of arylboronic esters from aryl halides or triflates now allows a one-pot, two-step procedure for the synthesis of unsymmetrical biaryls (Scheme 1-41) [147]. The synthesis of biaryls is readily carried out in the same flask when the first coupling of the triflate with diboron 82 is followed by the next reaction with another triflate. The synthesis of naturally occurring biflavanoids and the couphng of N-(phenylfluorenyl)amino carbonyl compounds to polymeric supports are reported [154]. 

Electron-rich aromatic systems can act efficiently as Michael donors, as shown recently by Krohn s group (Scheme 2.46) [111]. For example, reaction of the enone 2-193 with the resorcine derivative 2-194 in a domino Michael/acetalization process led to various naturally occurring xyloketals of type 2-196 in excellent yield. 

A short enantioselective synthesis of (-)-(R,R)-pyrenophorin, a naturally occurring anti-fun-gal 16-membered macrolide dilactone, is prepared from (S)-5-nitropentan-2-ol via the Michael addition and Nef reaction (Scheme 4.23).162 The choice of base is important to get the E-alkene in the Michael addition, for other bases give a mixture of E and Z-alkenes. The requisite chiral (S)-5-nitropentan-2-ol is prepared by enantioselective reduction of 5-nitropentan-2-one with baker s yeast.163... 

A useful approach for the preparation of chiral (3-aminophospho-nic acids from the naturally occurring a-amino acids has been reported.139 The overall scheme (Equation 3.4) involves formation of the phthalimide-acid halide from the starting a-amino acid followed by a Michaelis-Arbuzov reaction with triethyl phosphite to give the acylphosphonate. Complete reduction of the carbonyl group in three steps followed by hydrolysis of the ester and amide linkages provides the target material in very high yield without racemization (>99% ee). 

Using trimethylsilyl triflate, a one-pot reaction of acetoxyallylation and O-silylation of nitrones, gave silylated hydroxylamines (673). Enantiomers of the naturally occurring alkaloid dihydropinidine, potential antifeedants against the pine weevil Hylobius abietis, were prepared by diastereoselective, dimethylzinc mediated addition of pinacolyl 2-propenylboronate to (/ )- and to (S )-2-methyl tetrahydropyridine-A-oxide, obtained from D-alanine and L-alanine, respectively (Scheme 2.190) (674). 

Zhang68 has applied the cyclization of esters to the formation of a-methylene-y-butyrolactones, thus offering a novel and enantioselective entry to these substructures. The importance of this unsaturated lactone is evidenced by its ubiquitous presence in nearly a third of all naturally occurring secondary metabolites. The Alder-ene reaction has been applied to a formal total synthesis of (+)-pilocarpine, a leading therapeutic reagent for the treatment of narrow and wide glaucoma. Zhang intersected Btichi s synthetic intermediate (i )-181 (Scheme 47) in only two steps with a 99% ee and a 91% overall yield. In comparison, Biichi synthesized (i )-181 in five steps with a 92% ee and a 20% overall yield. 

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