Of dihydropyrrole

Pyrrole fails to undergo a Heck reaction with 1-bromoadamantane [90], However, dihydropyrroles such as 131 and 132 undergo Heck reactions with ease, although the yields are variable [91-93]. Some examples are illustrated below. Since dihydropyrroles can be oxidized to pyrroles with a variety of reagents [94, 95], these Heck reactions of dihydropyrroles should constitute viable routes to pyrroles. 

In these Heck reactions some degree of enantioselectivity (up to 83% ee) is achieved in the presence of (/ )-BINAP, although the yields of Heck products are often very low in the highest degree of enantioselectivity (e.g., 19% isolated yield at 83% ee) [93]. An example of a tandem Heck reaction is shown below involving the arylation of dihydropyrrole 132 with 1-naphthyl triflate (133) [92]. Complete chirality transfer is observed for the arylation of 134 to 135. 

With regard to the Pd-catalyzed arylation of dihydropyrroles presented in Section 2.5, it is noteworthy that the readily available 2,5-dihydropyrroles 197 can be smoothly isomerized to 2,3-dihydropyrroles 198 under the influence of Pd [144],... 

Many other examples, even with less reactive imine precursors as electrophiles, demonstrate that this type of dihydropyrrole synthesis has a very broad range. Eqs 8.21-8.24 present selected examples of the addition of lithiated methoxyallene 42 to... 

Dihydrooxazin-2,3-diones can be prepared by Baeyer-Villiger oxidation of dihydropyrrole-2,3-diones (Equation 51, Table 9). 

Further study with Rh2(OAc)4-catalyzed reaction styryldiazoacetate 188 and cinnamaldehyde derived imine 189 found the formation of dihydropyrrole 190 and dihydroazepine 191 in high yields and with high stereocontrol. No aziridine products were observed in these cases (Equation (29)). ... 

Another application was described by Reissig et al. with the cyclization of alkoxyallenes. The most relevant finding reported in this paper was the obtainment of aromatic pyrrole, with the absence of dihydropyrrole product [44]. 

Three types of dihydropyrrole (11-13) and two types of dihydro-furan and -thiophene exist (12-13), but only a single class of tetrahydro compounds (14). 

There are two possible types of dihydro-furans and -thiophenes (cf. 214, 215) and examples of both are known. There are three possible classes of dihydropyrroles /V-unsubstituted 2-pyrrolines (216) are in tautomeric equilibrium with the corresponding 1-pyrrolines (217). 

The homologous azirine (143) with a one-atom bridge gave quite different results.70 Photolysis led to the 3,5-fused bicyclic dihydropyrrole (144). The isomeric azirine (145) also led to (144), although the initial products included dihydropyrrole (146) which apparently converted to (144) as photolysis continued. Azirines (143) and (145) were shown to not interconvert and die postulated two discrete azomethine ylides were trapped with methyl trifluoroacetate. Formation of dihydropyrrole (144) was explained based on a two-step cycloaddition process involving a common diradical intermediate. The observation of (146) from photolysis of (145) but not (143) can be explained based on extinction coefficient differences. Azirine (145) has a high extinction coefficient as does (146). The initial product (146) can then be optically pumped to (144) with a low extinction coefficient. Azirine (143) also has a low extinction coefficient and any (146) that formed from it would be optically pumped to (144) before observa-... 

A variety of five-membered nitrogen heterocycles can be prepared efficiently by inter- or intramolecular addition/cyclizations of sulfonamide anions with alkynyliodonium salts. The intermolecular variant employs the combination of the amides 172 or anilides 174 with propynyl(phenyl)iodonium triflate (Scheme 65) [131,132]. The yield of dihydropyrroles 173 in this cyclization is extremely sensitive to the nature of the protective group P the tosyl group in 172 proved... 

This method provided an efficient access to cyclopentylamine-containing alkaloid skeleta. Similarly, by using 1-propynyl phenyliodonium triflate and various tosyl-amide anions, the preparation of dihydropyrroles and indoles was reported [72]. 

Electrophile-mediated cyclization reactions of alkynes tethered to pendant heteroatom nucleophiles is an emerging strategy for the synthesis of heterocycles. This methodology has now been applied to the synthesis of pyrroles. The iodocyclization of 3-aminoalkynes 1 led to the formation of dihydropyrrole 2 <07TL7906>. Treatment of the latter with mesyl chloride in the presence of triethylamine then gave (i-iodopyrrolcs 3. 

In this chapter, we describe our effort to develop GGTIs with novel scaffolds [13,14]. Our approach commenced with the constrnction of a novel library of dihydropyrroles and tetrahydropyridines derived from the phosphine-catalyzed annulation of resin-bound allenoates and A-sulfonyl imines. Derivatization of one of the initial hits, dihydropyrrole-carboxyhc... 

Azomethine ylides can also be trapped by aryl trifluoromethyl alkynes. When l-t-butyl-2-cyano-aziridine was used, a pyrrole was formed by elimination of hydrogen cyanide <94S287>. Use of aziridine-2-carboxylate esters with this dipolarophile gave regioisomeric mixtures of dihydropyrroles which could be converted to pyrroles by oxidation with ddq (Equation (60)). 

Sulfinamide 491, upon treatment with m-CPBA in toluene, yielded in an unisolated mixture of diastereomeric epoxides subsequent electrophilic cyclization using a catalytic amount of camphor-10-sulfonic acid (CSA) afforded a 75 25 mixture of sulfonyl dihydropyrroles 492 in 73% yield (Scheme 4.148). Treatment of the more acidic sulfinamide 494 with TBATB in the presence of K2CO3 gave cyclic products 495 in moderate yields, mainly as 2,5-cis isomers. Either further bromination of dihydropyrroles 492 or oxidation... 

Scheme 10.10 Synthesis of dihydropyrroles through hydrogen-bonding-activation mode.

The selective formation of dihydropyrrole 308 from the thermolysis of bis-azirine (307) was rationalized on the same basis. 

The reaction of azomethine ylide formed from the aziridine 77a with trifluoro-methylaryl acetylenes gave a mixture of dihydropyrroles 109 and 110, which formed a 1 3 mixture of pyrroles 111 and 112 by oxidation with DDQ [49]. 

Scheme 42.47 Synthesis of dihydropyrroles by 1,3-dipolar cycloaddition using conjugated ynones catalyzed by phosphoric acid catalyst 101a.

Very recently, Sun et al. developed a cascade reaction with a binary catalytic system combining a secondary amine and a palladium catalyst for the synthesis of dihydropyrrole enantioselectively [54]. The reaction began with a Jprgensen-Hayashi catalyst promoted N-Ts propargyl amine-involved aza-Michael addition to cinnamaldehydes and ended with subsequent PdCl and Jprgensen-Hayashi catalyst co-promoted car-bocyclization (Scheme 9.59). The chemistry presented here also involved a DYKAT process and provided an alternative to chiral dihyropyrrole synthesis. 

Double alkenylatirai of amides with (lZ,3Z)-l,4-diiodo-l,3-dienes 124 could produce di- or trisubstituted Al-acylpyrroles 125 with good to excellent yields (Scheme 44) [80]. The same idea has been applied in the synthesis of dihydropyrroles and carbazoles [81]. 

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