Add Catalyzed Cyclizations

Another cationic-cationic domino reaction which follows the way of biosynthesis is used by Koert et al for the synthesis of the whole left part of the polyether etheromydn.1141 The starting step is an add catalyzed cyclization of a diepoxide to give a bistetrahydrofuran with creation of three new oxa-cycles in over 30 % yidd. 

The transformation of catalyzed cyclization of acyclic compounds 75). 

Pseudodiosgenin 0(26)-tohienesulfonate (172) reacted with methylamine to give the 26-methylaminofurostadienol 173. Add-catalyzed cyclization of 173 afforded 174 with an MS indicative of a spiroaminoketal (spirosolane) structure (prominent peaks at m/e 128, 152, and 427 see Table VI). Compound 174 was shown to differ from a previously synthesized IV-methyl-solasodine both compounds seem to differ in stereodiemistry (C-22 ) (225). Isomerism of V-methyl- and V-formylsolasodine derivatives causeid by nitrogen inversion is discussed by Kusano et al. (226). 

The chemical simulation of this biosynthetic process has been developed as an important methodology in organic synthesis. Van Tamelen reported the add-catalyzed cyclization of chiral terminal epoxides of polyprenoids [11]. In contrast, Johnson adopted the acid-catalyzed cyclization of poly-prenic acetals derived from chiral diols [12]. In addition to these pioneering studies, the biomimetic polyene cycliza-tions of polyprenoids, which are induced by a variety of electrophiles such as proton, oxonium ion, halonium ion [13], or metal ion [14], have also been developed. Despite extensive studies on these diastereoselective olefin cyclizations, enantioselective processes using synthetic chiral catalysts had not been developed for a long time. In 1999, Yamamoto s... 

Carbon nucleophiles can also add to in situ generated vinylidene species. Thus, ruthenium-catalyzed cyclizations of dienylalkynes produced arene derivatives [55] (Eq. 41). 

IV-Allylthioureas and thioamides (385) undergo an acid-catalyzed cyclization to A2-thiazolines (387). The reaction proceeds through the carbenium intermediate (386 Scheme 236) (70JOC3768). In a similar way, a-isothiocyanatoacrylates (388) add alcohols or thiols affording intermediate a-thioacylaminoacrylates (389) which cyclize under acid or basic conditions to 2-substituted A2-thiazoline-4-carboxylates (390 Scheme 237) (76LA1997). 

Another Lewis add-catalyzed atom-transfer domino radical cydization, to produce various bicydic and tricyclic ring skeletons, has been developed by Yang and coworkers [54], Reactions of the a-bromo- 3-keto ester 3-125 with Yb(OTf) 3 and Et3B/02 led to the bicyde 3-126 in 85 % yield (Scheme 3.33). The reaction proceeds via a 6-ertdo-trig and 5-exo-trig cyclization after initial abstraction of the bromine... 

In 1997, the controversial mechanism of the Biginelli reaction was reinvestigated by Kappe using NMR spectroscopy and trapping experiments [94], and the current generally accepted process was elucidated (see Scheme 9.23). The N-acyliminium ion 9-112 is proposed as key intermediate this is formed by an add-catalyzed reaction of an aldehyde with urea or thiourea via the semiaminal 9-111. Interception of 9-112 by the enol form of the 1,3-dicarbonyl compound 9-113 produces the open-chain ureide 9-114, which cyclizes to the hexahydropyrimidine 9-115. There follows an elimination to give the final product 9-116. 

The carbopalladation is a central reaction in organopalladium chemistry and is extensively presented in Part IV. hi most reactions, a discrete organopalladium intermediate adds to a donble or triple bond. In this section, the reaction of an alkyl iodide with di-ethylzinc in the presence of a palladium(O) catalyst is presented. Such reaction conditions generate an alkyl radical that readily adds intramolecularly to a double bond, leading to an organozinc derivative (Scheme 1). The combination of a radical cyclization with the formation of an organometallic product allows new synthetic applications that will be discnssed. Closely related Ni-catalyzed cyclizations will also be briefly presented. 

In 2006, the group of Artok showed that 5-aryl-2(5H)-furanones could be prepared in moderate to good yields by a rhodium-catalyzed carbonylative arylation of internal alkynes with aryl boronic acids (Scheme 1.9a) [22]. a,P-Unsaturated ketones (chal-cone derivatives) were formed as the major product when some TFA (trifluoroacetic acid) was added under the same reaction conditions [23a]. By varying the catalytic system, indanones could be produced as the main product [23b]. The chemical behavior of terminal alkynes is different, and either a,P-unsaturated ketones or furans starting from propargylic alcohols can be achieved (Scheme 1.9b) [24, 25]. In the case of vinyl ketones, 1,4-diketones were obtained by rhodium-catalyzed coupling of arylboronic acids in the presence of 20-40 bar of CO [26]. In 2007, Chatani demonstrated that indenones could be accessed by a carbonylative rhodium-catalyzed cyclization of alkynes with 2-bromophenylboronic adds (Scheme 1.9c) [27]. Here, the key intermediate is a vinylrhodium(I) spedes that is formed by transmetaUation of RhCl with 2-bromophenylboronic acid followed by insertion of... 

Toste and coworkers reported the first asymmetric intramolecular hydrocarboxylation of an allene by combining a chiral ligand with a chiral counterion on a Au(I) catalyst (Scheme 2.27). Chiral ion pair formation was crucial to the high selectivity [69[. In another account, a related carboxyallene species was proposed to be an intermediate in a Pd-catalyzed cyclization of alkynoic adds [70]. 

As discussed in Sect. V.3.5, halide ions can also add to the palladium 7r-complexes, and the process may be termed halopalladation. Addition of Pd and a halogen, such as Cl and Br, to olefins, acetylenes, allenes, and conjugated dienes has been reported. However, most of the currently useful reactions initiated by halopalladation involve the use of alkynes as the substrates. Halopalladation of aUcynes gives vinylpalladium intermediates, which can undergo intramolecular carbopalladation to form cyclized products. Pd-catalyzed cyclization of ally lie aUcynoates can produce 7r-alkylidene-y-butyrolactones, which represent a basic structural unit in a wide variety of biologically active natural products. 

Although aU attempts to cyclize the free alcohol 325 (R= H) failed completely, the corresponding silylether (R = SifCHjjj) on heating to 170° provided the cycloadduct 326 in 75% yield and the same configuration (see 328) resulted from the diethyla-luminum chloride catalyzed reaction of the corresponding pivalate. In contrast to this, the Lewis add-catalyzed cydoaddition of the TBDMS ether (325, R=TBDMS) gave rise to the P-substituted compound 327. A detailed explanation of this outcome is not easy in this case, but the fact that the TBDMS ether needs only 1.1 equiv of the Lewis add while the pivalate requires 2.5 equiv of the catalyst indicates that coordination with the catalyst determines the structure of the transition state, leading either to 327 or 328. 

Notably, the reaction is not prevented by the basic amine, suggesting that the initial gold-catalyzed cycUzation must be facile. 149 can then proceed through Lewis acid-or Brpnsted add-catalyzed formation of the N-acyl iminium ion 150, which cyclizes to yield the final product 147 in an excellent yield. 

A cascade reaction involving 1,3-dipolar cycloaddition of ketenimine was reported by Li et al. [69], The transformation combines a CuAAC reaction, a Lewis add-catalyzed 6-endo cyclization of Af -(2-alkynylbenzylidene)hydrazide, a [2+3] cycloaddition, and an aromatization in a single step to afford 2-amino-//-pyrazolo[5,l-a] isoquinolines 102 in good to excellent yields (Schane 5.66). The copper-catalyzed three-component reaction of sulfonyl azides, alkynes, and nitrones also involves 1,3-dipolar cycloaddition between ketenimine and nitrone (Scheme 5.67) [70]. The nitrone substrates in this transformation could be generated in situ from benzalde-hydes and hydroxylamines. 

We can add to these methods the acid-catalyzed cyclization of the natural germacranolide gallicin that generates, among several products, the 1,4-epoxyeudesmanolide 116 that contains a tran -fused decalin moiety (Scheme 13). Under the same conditions, the closely related Sa-hydroxygaUicin, 117, is cyclized into shonachalin B with a cis-fused decalin system. These reactions proceed through cationic intermediates 114,115, and 118 [154] (Scheme 16). 

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