Pyridines annulated

Boger and others (82JOC3761 82JOC3763 83JOC623 85JA5754) used this pyridine annulation for the formal total synthesis of antitumor, antibiotic streptonigrin (63) by an intermolecular Diels-Alder reaction between 1,2,4-... 

One Nitrogen Atom (it is self-subdivided into Pyridines, Pyridinium Compounds, Ylides, Pyridine N-Oxides, Applications of Pyridines, Bipyridines and Related Systems, Hydropyridines, Biologically Active Pyridines and Hydropyridines, Pyridines Annulated with Carbocycles, Pyridines Annulated with Heterocycles). 

A series of 2-(4-(1,X-naphthyridinyloxy)phenoxy)propan-oic acids were prepared for evaluation as potential grass herbicides and to assess their ability to inhibit maize acetyl-CoA carboxylase (ACCase). A new regiospecific pyridine annulation procedure was employed to prepare the key 2-chloro-l,6-, 1,7-, and 1,8-naphthyridine intermediates. Of the compounds prepared, only the 6-chloro-l,5-naphthyridinyloxyphen-oxy propanoic acid displayed substantial levels of herbicidal activity. The relative levels of herbicidal activity in this series of propanoic acids could be explained by the ability of these materials to inhibit ACCase. 

In conclusion, we have employed a novel, regiospecific pyridine annulation procedure to prepare a series of l,X-naphthyridinyloxy-phenox rpropanoic acids as potential herbicides. The wide variation in herbicidal activity among this seemingly very similar group of acids clearly demonstrates the importance of the nature of the heterocycle in this area of chemistry. 

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

Annulation of pyridine to indole is accomplished by a tandem aza-Wittig/electrocyclization strategy as shown in Eq. 10.68."... 

One representative of the oxazolo[4,5-/][ 1,6]naphthyridine system, viz. the ester 62, is produced in four steps by annulation of 2-(dicthy lam ino)oxazolo[4,5- pyridine (Scheme 20). Whether the final product exists mainly as the hydroxy tautomer or as the 9//-6-one cannot be deduced from the spectral data presented alkylation occurs either at the oxygen or at N-9, and gives either 63 or 64 <1993SC2931>. 

T6036>. It should also be mentioned that an isomeric series of thieno[2,3- >]pyridines has been prepared by base induced annulations involving for instance 2-mercaptopyridine-3-carbonitrile precursors and ethyl chloroacetate <06SC97>. 

Workers at Merck recently reported three variants for pyridine formation in conjunction with the synthesis of COX-2-Specific inhibitor 8 (Scheme 1). Acid catalyzed annulation (path a) was achieved in 72% with 2 equivalents of methanesulfonic acid and four equivalents of 2-chloro-3-aminoacrolein. Base-promoted annulation between 7 and 2,3-dichloroacrolein provided 8 in 58% yield. Finally, base-promoted annulation with 2-chloro-iV,jV-dimethyl-armnotrimethinium hexafluorophosphate afforded 8 in 97% yield . Other alkylation-based strategies for pyridine formation include the work of Manna <00BMC1883> and Parra <00S273>. 

Smith and co-workers have recently expanded the scope of the [4+1] radical annulation reaction between isonitriles and 1-iodoalkynes to include vinylisonitriles <00JCS(P1)641>. Thus, vinylisonitrile 17 and iodide 18 afford annulated pyridine 19. 

A three-component coumarin synthesis involves the Pd-catalysed coupling of o-iodophenols with alkynes and subsequent insertion of carbon monoxide. With internal alkynes, pyridine is the crucial base for successful annulation the regioselectivity with unsymmetrically substituted alkynes is only moderate (Scheme 43) . 

Pyridine-containing tricyclic compounds have been produced via a sequence consisting of a Suzuki reaction and a subsequent annulation. Gronowitz et al. coupled 2-formylthienyl-3-boronic acid with 3-amino-4-iodopyridine. The resulting adduct spontaneously condensed to yield thieno[2,3-c]-l,7-naphthyridine 59 [47]. They also synthesized thieno[3,4-c]-l,5-naphthyridine-9-oxide (60) in a similar fashion [48]. Neither the amino nor the N-oxide functional group was detrimental to the Suzuki reactions. 

In a sequence analogous to the Suzuki reaction and annulation described in section 4.2.4, pyridine-containing tricyclic compounds have also been prepared via the Stille reaction and a ... 

The acyclic version of Larock s heteroannulation was successfully applied to the synthesis of highly substituted pyridines [166]. The annulation of rert-butylimine 210 with phenyl propargyl alcohol produced pyridine 211 regioselectively in excellent yield. The regiochemistry obtained was governed by steric effects. Furthermore, the choice of imines was crucial to the success of the heteroannulations. terr-Butylimine was the substrate of choice, since all other imines including methyl, isopropyl, allyl and benzyl imines failed completely to produce the desired heterocyclic products. 

The Chichibabin reaction for the synthesis of indolizines has been revisited and some variations have been proposed. The modified benzotriazole 168 reacted with substituted pyridines 167 in refluxing dimethylformamide (DMF). The indolizine 169 bears a triazole moiety that proved useful for the construction of benzo-annulated indolizines <2000JOC8059>. Also, cyclic iminium ylides like 170 can be used in the Chichibabin reaction. Their solvolysis produced the corresponding indolizinones 171 (Scheme 40). 

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