Cyclization Cyclopropanation

Owczarczyk, Z., Lamaty, R, Vawter, E.J. and Negishi, E.-i. (1992) Apparent endo-mode cychc carbopalladation with inversion of alkene configuration via exo-mode cyclization-cyclopropanation-rearrangement./. Am. Chem. Soc., 114,10091-2. 

Grigg et al. [41] first described a cyclization-cyclopropanation process which was later on developed further by de Meijere s group. It is a nice example of a domino process with four C—C bonds being formed in a single transformation [42]. Thus, reaction of 64 with Herrmann-Beller catalyst (15) furnished 66 as the only product. It can be assumed that the palladium compound 65 is an intermediate (Scheme 8.14). 

Isoxazolidine-fused P-lactams 85 were synthesized through a base-promoted cyclization-cyclopropane ring opening of 4-spirocyclopro-paneisoxazolidines 84 prepared in turn by 1,3-DC of N-aryl C-carbamoylnitrones and 2-arylmethylidenecyclopropanedicarboxylates (13T5173). 

Nandi, S., Ray, J. K. (2009). Palladium-catalyzed cyclization/cyclopropanation reaction for the synthesis of fused N-containing heterocycles. Tetrahedron Letters, 50,6993-6997. 

Cyclic a-diazocarbonyl compounds (59) and enynones (61) have been used as Rh-and Zn-carbenoid precursors, respectively. Cyclic derivatives (59) have been found to favour intermolecular Rh-catalysed cyclopropanation reactions, relative to the formation of conjugated alkene (60) by intramolecular -hydride elimination as is usually observed in the case of a-alkyl-a-diazocarbonyl compounds this high level of chemoselectivity is reported for the first time. Rh-carbenoids derived from (59) have also promoted cyclo-propenation reactions as well as diverse X-H insertion reactions (i.e., X = C, N, O, S). In parallel, highly functionalized cyclopropylfiirans (62) have been successfiilly prepared from an alkene and an enynone (61) by a cyclization/cyclopropanation sequence conducted in the presence of catalytic amounts of ZnCl2, which is cheap and of low toxicity computations support the probable participation of intermediate Fisher-type Zn(II) carbene complexes (63). 

The dienyne 394 undergoes facile polycyclization. Since the neopentylpalla-dium 395 is formed which has no hydrogen /J to the Pd after the insertion of the disubstituted terminal alkene, the cyclopropanation takes place to form the tt-allylpalladium intermediate 396, which is terminated by elimination to form the diene 397(275]. The dienyne 398 undergoes remarkable tandem 6-e. o-dig. 5-cxo-trig. and -exo-trig cyclizations to give the tetracycle 399 exclu-sively(277]. 

In the reaction with epoxides, y-hydroxysulfones are obtained278-280. For example, Kondo and coworkers279 synthesized various (5-lactols 226 by treating sulfone acetals 225 with terminal epoxides as shown below. Dilithiated phenylsulfonylmethylene reacted with haloepoxide and afforded 3-(phenylsulfonyl)cycloalkanols281. Treatment of y, 5-epoxysulfones 227 and 229 with n-butyllithium resulted in cyclization to form cyclopropane derivatives 228 and bicyclobutane 230, respectively282. 

Treatment of a-lithionitriles with vinylic sulfones resulted in the formation of cyclized products, i.e., 3-oxothian-l, 1-dioxides 346 or cyclopropane derivatives 348. When a-lithiated aliphatic nitriles were used, carbanions 343, formed by the nucleophilic addition,... 

The cyclopropane cyclizations by elimination of triflinic acid (CF3S02H) are readily effected by basic treatment of triflones (trifluoromethyl alkyl sulfones) with activated /-protons (equations 46 and 47)39. The cyclopropane diesters 45 are formed on treatment of 44 with potassium hydride in DMSO or sodium methoxide in methanol (equation 48). In contrast, the monoester 46 failed to give the desired cyclopropane40. Addition of carbanions derived from /f, y-unsaturated phenyl sulfones to a, /i-unsaturated carboxylic esters and subsequent elimination of benzenesulfinate ion give cyclopropanes possessing the unsaturated side chain and the ester function in trans positions (equation 49)41. 

The conjugate addition of 103 to phenyl vinyl sulfone (53) proceeds under phase-transfer conditions. The yield of cyclopropanes in the following cyclization is low for synthetic purposes (equation 84)69. 

When ( )-l-methylsulfonyl-2-phenylethylene (105) was allowed to react with a-lithio-nitriles (106) in THF at — 60 to — 70 °C and then under reflux, 3-oxothiane 1,1-dioxides (107) were obtained in good yield, and no cyclopropanes were formed (equation 86)71. On the other hand, a-lithiophenylacetonitrile (106, R1 =Ph) reacted with 105 to give the cyclopropane 108 in good yield. Yields obtained in this cyclization are listed in Table 9 (equation 87)71. 

The rearrangement of the intermediate alkyl cation by hydrogen or methyl shift and the cyclization to a cyclopropane by a CH-insertion has been studied by deuterium labelling [298]. The electrolysis of cyclopropylacetic acid, allylacetic acid or cyclo-butanecarboxylic acid leads to mixtures of cyclopropylcarbinyl-, cyclobutyl- and butenylacetamides [299]. The results are interpreted in terms of a rapid isomerization of the carbocation as long as it is adsorbed at the electrode, whilst isomerization is inhibited by desorption, which is followed by fast solvolysis. 

When free radicals are added to 1,5- or 1,6-dienes, the initially formed radical (9) can add intramolecularly to the other bond, leading to a cyclic product (10). When the radical is generated from an precursor that gives vinyl radical 11, however, cyclization leads to 12, which is in equilibrium with cyclopropylcarbinyl radical 13 via a 5-exo-trig reaction. A 6-endo-trig reaction leads to 14, but unless there are perturbing substituent effects, however, cyclopropanation should be the major process. 

Larock has developed a new catalyst system for the Pd-catalyzed cyclization of olefinic tosylamides. Whereas typical conditions require either stoichiometric amounts of Pd(II) salts or catalytic amounts of Pd(II) in the presence of benzoquinone as a reoxidant, the new catalyst system utilizes catalytic Pd(OAc)2 under an atmosphere of O2 in DMSO with no additional reoxidant <96JOC3584>. Although o-vinylic tosylamides 76 can be cyclized to Af-tosylindoles 77 using this catalyst system, PdCla/benzoquinone is more effective for such cyclizations. Interestingly, in the case of o-allylic tosylanilides, the cyclization can be modulated to afford either dihydroindole or dihydroquinoline products. In a related approach involving a common 7i-aUyl Pd-intermediate, 2-iodoanilines were coupled with vinylic cyclopropanes or cyclobutanes in the presence of a Pd catalyst to afford dihydroindoles <96T2743>. 

The synthesis of different substituted finans by cyclization of 4-pentynones using potassium tert-butoxide in DMF was reported <96TL3387>. Dihydrofuran 32 can be prepared by a destannylative acylation of l-[(2-methoxyethoxy)methoxy]-2-(phenylsulfonyl)-2-(tributylstannyl)-cyclopropane. Treatment of 32 with BFj-EtjO yields 3-acyUurans via an intramolecular Prins-type reaction of the resulting oxonium ion intermediate <96TL4585>. 

Key features of the cyclopropanation include the ylide acting as a mild base to isomerize the 1,2-dioxines into cis-y-hydroxy enones, followed by Michael addition of the ylide and last by cyclization of the intermediate enolate [35]. It must be noted that the trans-y-hydroxyenones do not give the cyclopropanation. 

Dendrimers 5-8 were obtained by taking advantage of the versatile regiose-lective reaction developed in the group of Diederich [24], which led to macro-cyclic bis-adducts of Cgg by a cyclization reaction at the C sphere with bis-mal-onate derivatives in a double Bingel cyclopropanation [25]. Reaction of the dendritic malonates with Cgg, I2, and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in toluene at room temperature afforded the corresponding cyclization products 5-8 (Fig. 2). The relative position of the two cyclopropane rings in 5-8 on the Cgo core was determined based on the molecular symmetry deduced from the and NMR spectra (Cs) as well as on their UV/Vis spectra. It is well estabhshed... 

Cyclopropyl sulfones were shown to be obtained either by cyclization of y-p-tosyloxy sulfones 232 with base or by treatment of phenylsulfonylacetonitrile 233a or ethyl phenyl sulfonyl acetate 233b with 1,2-dibromoethane in the presence of benzyltriethyl-ammonium chloride (BTEA) and alkali in good yields. Chang and Pinnick synthesized various cyclopropane derivatives 234 upon initial treatment of carbanions derived from cyclopropyl phenyl sulfone with either alkylating agents or a carbonyl compound and subsequent desulfonylation, as shown below. 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

Organic halides play a fundamental role in organic chemistry. These compounds are important precursors for carbocations, carbanions, radicals, and carbenes and thus serve as an important platform for organic functional group transformations. Many classical reactions involve the reactions of organic halides. Examples of these reactions include the nucleophilic substitution reactions, elimination reactions, Grignard-type reactions, various transition-metal catalyzed coupling reactions, carbene-related cyclopropanations reactions, and radical cyclization reactions. All these reactions can be carried out in aqueous media. 

The catalytic conditions are well suited for the preparation of cyclopropanes provided that a, /J-unsaturated carbonyl compounds are employed as radical acceptors (formation of electrophilic radicals after cyclization) as shown in Scheme 32 [123]. 

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