One-pot cyclization

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

A reaction related to alkene-aldehyde coupling is the alkene-imine coupling. A one-pot cyclization involving such a reaction (Eq. 3.27) proceeds smoothly in a mixture of water-THF. The reaction has been used in the asymmetric synthesis of pipecolic acid derivatives.114... 

Alder-Ene Reactions. An ene-iminium one-pot cyclization proceeds smoothly in a mixture of water-THF (Eq. 12.66). 138 The reactivity of the ene-iminium substrates is highly dependent on the substitution pattern of the ethylenic double bond. This methodology can be used to form homochiral pipecolic acid derivatives. 

Dioxatetraazaperhydroanthracenes 98 were prepared by one-pot cyclization reaction of hydrazinoethanols 97 with aldehydes in aqueous solution (Equation 6) <1996JOC4125>. 

A one-pot cyclization of substituted disilanes to 99 is shown in Equation (7) <2004CL24>. 

Compounds 68 have been obtained by one-pot cyclization of acyclic tetraamine 122 with ct-dicarbonyl reagents. This synthesis is not stereoselective, providing a mixture of vicinal isomers cis/trans of the bis-aminal 68 (Equation 11) <1998TL6861, 2003EJ01050, 2003T4573, 2005JOC7042>. 

Methoxypyrazine-2-one Af-oxides 341 were prepared from oxime derivatives 340 by one-pot cyclization in the presence of DCC/DME with subsequent interaction with Me2S04/K2C03 and NaOH (equation 148) . Similar intramolecular cyclizatiou of ester and oxime O-ethers groups iu the presence of lithium arylthiolate also leads to pyrazin-2-one ring formation . ... 

It was thought that protection of the anthranilic nitrogen could prevent competing and undesired participation in the Ugi reaction, a potential explanation for the moderate yields reported for the parent synthetic route.7 Boc removal and cyclization to BDP could be sequentially achieved on treatment with acid in one pot. Cyclization may potentially occur upon acid treatment via any of the three intermediates 4, 5, and 6. Syntheses of five BDPs, designated 8, 9,10,11, and 12 (Fig. 1) were evaluated with isolated yields from 70 to 95%. 

Scheme 16 A microwave-promoted three-step one-pot cyclization...

Though 9S3 (64) in the meantime has also been obtained in 60% yield by cyclization with a molybdenum template [67], the cesium method is nevertheless advantageous on account of the simplicity of the one-pot-cyclization procedure... 

DiMauro and co-workers [67] have developed a rapid and efficient synthesis of 3-amino-imidazopyridines 16 using a microwave-assisted one-pot cyclization. The intermediate 15 was further reacted with various aryl bromides in the presence of a catalytic amount of Pd(dppf)Cl2 to yield the target compounds 16. The reaction scope is quite broad with respect to the aldehyde and aryl bromide components which might be electron-rich, electron-poor, aromatic, aliphatic, or sterically encumbered (Scheme 15). 

Scheme 43. Phenylselenyl Sulfate Catalyzed One-Pot Cyclization Reactions...

As discussed in Sect. 2, a-selanylalkyllithiums, generated from selenoacetals, can react with various electrophilic reagents, i. e. chloromethyl isopropyl ether for the synthesis of la-hydroxy vitamin D analogues [25] and with propargylic chloride derivatives for the preparation of alkynols [26]. A synthesis of vinyl-cyclopropane derivatives from l,4-dichloro-but-2-ene was achieved with trans stereoselectivity (>93%) in 68-89% yield. This one-pot cyclization, via an intramolecular allylic substitution, required the presence of two equivalents of u-BuLi [26] (Scheme 23). 

A chiral cyclopentenoid building blodt (60) has been reported to result in a one-pot cyclization process from epoxide (59) (readily accessible from (R,R)-(+)-taitaric acid) with the carbanion derived from (phenylthio)acetonitrile (equation 29). ... 

The functionalized phane tetracation 30 was synthesized by Harriman and coworkers [41] in a one-pot cyclization from 2,5-dibromomethylbenzoic acid and 4,4 -bipyridine via a zwitterionic structure. 

Derivatives of systems (64), (72), and (76) have been synthesized by one-pot cyclization of acyclic substrates. 

One-pot cyclization of acyclic substrates provides a facile synthetic entry to substituted derivatives of (103) and (113). 

This section covers cyclizations to the pyrrole nucleus catalyzed by other metals (Ti, Mn, Ru, Pd, Pt, Zn, In). Dembinski and co-workers used zinc(II) chloride as ligand-free catalyst for the microwave-assisted cyclization of homopropargyl azides 26 to afford substituted pyrroles 27 (Scheme 8) [62]. A similar methodology for the synthesis of 2,4,5-trisubstituted pyrroles was described by Driver et al. employing substituted 1-azidobuta-l,3-dienes in a cyclization reaction using catalytic amounts of zinc(ll) iodide [63]. A three-component zinc-catalyzed one-pot cyclization of aromatic and aliphatic propargylic acetates, silyl enol ethers, and primary amines to substituted pyrroles has been described by Zhan et al. The reaction sequence includes propargylation of the silyl enol ether, amination, 5-exo-(7ig-cyclization, and isomerization [64]. Hiroya and co-workers have shown... 

Synthesis of butenolides by one-pot cyclization reactions of silyl enol ethers with oxalyl chloride 06SL3369. 

A general synthesis of butenoUdes taking advantage of one-pot cyclization of sUyl enol ethers with oxalyl chloride was developed by Danger and appUed to a number of synthetic problems. This useful methodology has recently been reviewed. ... 

The Hantzsch reaction has also been incorporated in a multi-component reaction described by Rao et al. to produce 2-pyrazol 4-yl-substituted diiazole system in one step. The reaction involves a one-pot cyclization to form thiazole, pyrazolone and cyclopropane rings via the reaction of aryl bromomethylketonewith, thiosemicarbazide, and a-acetyl-y-butyro lactone in phosphorus oxychloride. 

TABLE 6. Synthesis of Hydroindanes One-Pot Cyclization of 2-Bromo-l,6-heptadienes and Snbseqnent One-Pot Diels-Alder Reaction (see Scheme 7)P2],23]... 

Representative procedure for the one-pot cyclization/halogenation of 2-alkynylanilines. 2-Butyl-3-iodo-lH-indole ° ... 

Cao, H., Jiang, H., Mai, R., Zhu, S. and Qi, C. 2010. Silver-catalyzed one-pot cyclization reaction of electron- deficient aUcynes and 2-Yn-l-ols An efficient domino process to polysuhstituted furans. Adv. Synth. Gated. 352 143-152. 

Sodium benzenesulfinate resin 43 can also be used to prepare a traceless solid-phase synthesis for 3,4-dihydropyrimidine-2-ones 54 and 55 (Scheme 12.13). This strategy highlighted the sulfinate acidification to yield resin-bound benzenesulfinic acid 52, followed by the condensation of urea or thiourea with aldehydes and sulfinic acid. A one-pot cyclization-dehydration process with 1,3-dicarbonyl compounds or )8-ketoesters (generated in situ by treating the latter reagents with KOH/EtOH) afforded 54, while cyclization with a mixture of pyrrolidine and /8-ketoacid in ethanol followed by the addition of TsOH HaO gave the ester form of 55. When THF was used as a solvent, the free carboxylic acid form of 55 was obtained in comparable yields. 

---