Domino cyclization derivatives

Scheme 1.24. Lewis acid-catalyzed cationic domino cyclization to give bicyclo[2.2.1]heptane derivatives.

Chiral information was introduced through the C3-building block 5 derived from lactic acid. The remaining two siereogenic centers in the natural product were provided under substrate control in the course of a domino cyclization... 

Synthesis of 9-substituted tetrahydroazepinopurines as asmarine analogs has been described <03T6493>. In relation to adenosine receptor antagonists, new derivatives of pyrazolo[4,3-c][l,2,4]triazolo[l,5-c]pyrimidines have been synthesized <03IMC1229, 4287>. A one-pot synthesis of l,2,4-triazolo[l,5-c]quinazoline thiones 65, consisting of a domino cyclization of 2-isothiocyanatobenzonitrile 63 with hydrazides 64 has been published <03EJO182>. 

Similarly, the dienynes 114 and 115 underwent a domino cyclization catalyzed by ruthenium complex 1 in good to excellent yields with generation of two cyclohexene rings embedded into the steroid-like derivatives 116 and 117, respectively (Scheme 2.42) [20bj. 

In 2013, Kim and coworkers reported a palladium-catalyzed domino cyclization of A-(2-bromoallyl)-A-ciimamyltosylamides for the construction of pyridines [4], The reaction proceeds via a domino 5-exo/3-exo carbopalladation, ring expansion by palladium rearrangement, and an aromatization. Various 4-arylnicotinate derivatives were produced in good yields (Scheme 2.2). 

A [4 + 2 +1] domino cyclization in water involving condensation of 2,2-dihydroxy-indene-l,3-dione (149), tetronic acid 150 and OPD catalyzed by acetic acid has been developed for the synthesis of spiro-substituted benzofurodiaz-epine derivatives 152 and 153 (Scheme 32) in a one-pot manner xmder MW proceeding within few minutes [102]. The authors observed that the outcome of tiie process was dependent on the ratio of reactants as well as on the electronic effects of the substituent in the aromatic ring of the diamine. 

SCHEME 32 A domino cyclization in water leading to benzofurodiazepine derivatives. 

C. Cheng, B. Jiang, S.-J. Tu, G. Li, [4+2+1] Domino cyclization in water for chemo- and regioselective synthesis of spiro-substituted benzo[i ] furo[3,4-e][l,4]diazepine derivatives. Green Chem. 13 (2011) 2107-2115. 

The cyclization to give the two pentafulvene units occurs in a tandem fashion. The domino cyclization to give naphthyl derivatives does not compete. The two benzopentafulvene moieties in bisfulvene 3.684 in its crystal are not in conjugation and have a twist angle at the central butadiene moiety of 88°. 

Scheme 3.8. Domino radical cyclization procedure in the synthesis of lysergic acid derivatives.

Itoh and coworkers [223] have shown that fullerene derivatives as 6/2-113, which to date have been prepared in a stepwise procedure, can be obtained in a three-component domino process by treatment of diynes 6/2-109, dimethylphenylsilane 6/2-110 and fullerene (C60) in the presence of a Rh-catalyst [223]. Interestingly, using maleic anhydride as dienophile failed to give the desired cycloadduct, whereas Cso -in spite of its strong tendency to form complexes with various transition metals [224] - never suppressed the catalytic silylative cyclization step to give the diene 6/2-112 (Scheme 6/2.24). 

The highly potent anti-HIV natural product daurichromenic acid (10-100) was synthesized by Jin and coworkers [36] using a microwave-assisted reaction of the phenol derivative 10-97 and the aldehyde 10-98 (Scheme 10.25). Normal heating gave the desired benzo[b]pyran 10-99 by a domino condensation/intramolecular SN2 -type cyclization reaction only in low yield. However, when the reaction mixture was irradiated twenty times in a microwave for 1-min intervals, 10-99 was obtained in 60% yield. This compound was then transformed into 10-100 by cleavage of the ester moiety. 

The reaction of the chloro ester 1-Me with 1,2-dinucleophilic 1,2-disubstituted benzene derivatives 161 in most cases gave the benzene-annelated six-member-ed heterocycles 162 in moderate yield (Scheme 50) [22b, 26,73]. The course of the domino-Michael addition-cyclization is also very sensitive to the nature of the base and the reaction conditions applied. Thus, only the primary Michael adducts... 

A domino Heck carbopalladation/cyclization reaction of (Z)-3-(2-(but-2-ynyloxy)phenyl)prop-2-en-l-ol 453 with aryl iodides furnishes chroman derivatives 454 in good yield (Equation 185) <2004AGE5997>. 

A recent paper explored the 1,2-functionalization of the allene moiety in monocyclic P-lactam allenynol derivatives under palladium-catalyzed reaction conditions <02CEJ1719>. Remarkably, a novel domino process, namely allene cyclization/intramolecular Heck reaction... 

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