One-pot approach

A convenient regioselective one-pot approach to pyrazolo[l,5-o]- and imidazolo[l,2-a]pyrimidine derivatives 79 from aminoheterocycles 78 and a,(3-unsaturated imines 77,... 

The estrogenic properties of isoflav-3-enes are well known and consequently, several derivatives of these chromene heterocycles have been the target of medicinal chemists. Varma and coworkers uncovered a useful enamine-mediated pathway to this class of compounds [142-144], Now the group has discovered a facile and general method for the MW-expedited synthesis of isoflav-3-enes substituted with basic moieties at the 2-position (Scheme 6.42) [145], These promising results are especially appealing in view of the convergent one-pot approach to 2-substituted isoflav-3-enes... 

More recently, a new and straightforward one-pot approach was reported by Bu et al. <2003JOC5415>. This reaction involves the cyclocondensation of l,2-dipyridin-2-yl-ethane-l,2-dione 120 and arylaldehydes, in the presence of ammonium acetate. Imidazo[l,5- ]pyridines 121 were obtained in reasonable yields, but competitive formation of imidazoles 122 was observed. The amount of ammonium acetate used in this reaction was also shown to strongly influence the yield of the cyclization (Scheme 38). 

The principal method for preparation of pyrazino[2,3- [l,3]oxazines, as reported in CHEC-II(1996) <1996CHEC-II(7)737> involves cyclization of a 2-aminopyrazine-3-carboxylic acid ester with an aromatic acid chloride. Further applications of this three-step approach have been reported <19948405, 2000BMC2803>, but a one-pot approach has also been developed (Equation 157). This cyclization has also been carried out using acetic anhydride in place of an acid chloride <2005JMT(741)67>. 

A new and efficient one-pot approach towards chiral 2-azetidinones has been reported to start from (25)-chloro-l-propanol. The treatment of this latter with 5 equivalents of pyridinium chlorochromate in dichloromethane at room temperature afforded the (2S)-chloropropanal which treated with 1 equivalent of amine and 1.5 equivalents of MgSC>4 yielded the (S)-N-(2-chloropropvIiclene)amines. Finally,... 

Diaryliodonium salts (diaryl-A3-iodanes) are widely used as arylating agents. There are a number of methods available for their synthesis typically involving two or three steps.378,379 A recent one-pot approach, however, offers a simple and high-yielding access to unsymmetrical diaryliodonium triflates using meto-chloroperbenzoic acid (mCPBA) as the oxidant380 [Eq. (4.111)]. Moreover, symmetrical diaryliodonium salts can directly be prepared from iodine and arenes without the use of expensive aryl iodides [Eq. (4.112)]. 

A microwave-assisted one-pot approach towards 2,4,5-trisubstituted oxazoles employed a hypervalent iodine (III) catalyst to bring about the reaction of ketones, 1,3-diketones and /3-keto-carboxylic acid derivatives with amides [75]. Microwave dielectric heating was also successfully utilized in a solid-supported, solvent-free synthesis of 2-phenyl-oxazol-5-ones (azlac-tones) [76] as well as in a solution phase synthesis of isomeric 2-phenyl-oxazol-4-ones (oxalactims) [77]. 

This microwave-accelerated double alkylation reaction was applicable to a variety of aniline derivatives and dihalides, furnishing N-aryl azacycloalkanes in good to excellent yields [89]. The reaction was applicable to alkyl chlorides, bromides and iodides and was extended to include hydrazines [90]. This improved synthetic methodology provided a simple and straightforward one-pot approach to the synthesis of a variety of heterocycles such as substituted azetidines, pyrrolidines, piperidines, azepanes, N-substituted-2,3-dihydro-Iff-isoindoles, 4,5-dihydro-pyrazoles, pyrazolidines, and 1,2-dihydro-phthalazines [91]. The mild reaction conditions tolerated a variety of functional groups such as hydroxyls, carbonyls, and esters. 

A variation of the one-pot approach that has, perhaps, been underdeveloped to date involves the use of multiple components (A and B), where the geometry of the reactants is designed to provide selectivity toward one macrocydic product, nA + nB An (Figure 6.1C). For example, Iyoda and coworkers exploited this approach to form selectively the cyclic trimer 8 based on the combination of a... 

Photoinduced nucleophilic substitution of aryl halides with potassium thioacetate. A one-pot approach to aryl methyl and diaryl sulfides. European Journal of Organic Chemistry, 2210-2214. 

Substituted pyrrolidines 46 can be prepared by a one-pot approach via the reductive cyclization of the precursor 45, which is prepared by conjugate addition of the -(alkylideneamino)nitrile 44 to methyl vinyl ketone (Scheme 34) C2005S945, CHEC-III(3.03.7)321>. 

A variety of other environmentally friendly strategies for the synthesis of quinolines were also reported. Goswami et al. developed a one-pot approach for the synthesis of quinolines from aromatic amines and P-aryl vinyl ketones under solvent and catalyst free conditions <07JHC1191>. In another solvent free one-pot method, Nagarajan et al. synthesized 3-quinolylcarbazoles from P-nitrovinylcarbazole and 2-amino acetophenone in moderate yields <07TL2489>. 

The reaction of substituted ketene acetals with alkenyl Fischer Cr carbene complexes provides a convenient one-pot approach to 4-aryl-3,4-dihydrocoumarins (Scheme 33)... 

A one-pot approach giving a series of l-(2-naphthyl)methylene- or l-(3,4-dimethoxybenzyl)pyrrolidines 432 has been developed, as illustrated by the reductive cyclization of the four-carbon precursor 433, which was prepared by conjugate addition of the a-(alkylideneamino)nitrile 434 to methyl vinyl ketone (Scheme 55) <2005S945>. 

The overall yields for the stepwise reaction with intermediate isolation of the enaminone 75 after the coupUng-addition sequence and its subsequent aza-annulation-Pictet-Spengler transformation fie in the same range as for the coupling-amination-aza-annulation-Pictet-Spengler sequence. However, avoiding the isolation and purification of the intermediate p-enanfinone favors the application of the one-pot approach. 

A novel one-pot approach for the synthesis of 2,4-disubstituted 3//-benzo[h] [1, 5]diazepines 115 has been disclosed by Muller and co-workers [163]. The compounds were obtained in good yields by the reaction of an acyl chloride, a terminal alkyne and a benzene-1,2-diamine via a consecutive one-pot, three-component Sonogashira coupling/Michael addition/cyclocondensation sequence, under micro-wave irradiation (Scheme 89). 

Sessler and coworkers have also developed a 3 -I- 2 approach to meso-diarylsapphyrins. This strategy, which is based on those used by Ogoshi and Smith ° to generate mc50-arylporphyrins, is outlined in Scheme 5.2.5. It involves the acid-catalyzed condensation of the diol 5.48 with the diacid tripyrrane 5.14. After oxidation with o-chloranil and chromatographic workup, diphenylsapphyrin 5.49 was obtained in ca. 3% yield. While less direct than the one-pot approach to 10,15-diarylsapphyrins outlined earlier (Schemes 5.1.6 and 5.1.7), this strategy allows synthetic access to isomeric 5,20-substituted diarylsapphyrins (e.g., 5.49). 

A special one-pot deprotection-transacylation method involves coupling of activated Fmoc amino acids with Aloc-protected amino acid esters.The Aloc-deprotection proceeds with palladium/phenylsilane in the presence of the acylating species. Using Fmoc-Phe-F the synthesis of the sterically demanding dipeptide Fmoc-Phe-(Me)Aib-OMe was accomplished in a yield of 65% A similar one-pot approach to the acylation of the even more difficult hindered and weakly nucleophilic a-trifluoromethyl amino acid esters involves the intermediate A-Teoc protection. Thus treatment of ( )-Teoc-a-(a-CF3)Leu-OMe with Fmoc-Gly-F and a catalytic amount of tetraethylammonium fluoride in acetonitrile at 50 °C for 1-2 weeks gave ( )-Fmoc-Gly-(a-CF3)Leu-OMe (77%... 

The metallation of diethyl 3-(trimethylsilyl)-l-propenylphosphonate with LDA at low temperature gives the delocalized allylphosphonate carbanion, which reacts regioselectively in the a-posi-tion with aliphatic or aromatic aldehydes to afford the corresponding P-alcohol as a mixture of diastereomers. " Subsequent dehydration with DCC in CH2CI2 at reflux in the presence of catalytic CUCI2 stereospeciflcally produces the desired 2-phosphonylated 1,3-dienes. A one-pot approach is based on the P-elimination reaction of an intermediate enol phosphate using z-BuOK. ... 

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