Regio- and enantioselective catalytic cyclization of pyrroles onto N-acyliminium ions

The regio- and enantioselective cyclization of pyrroles onto N-acyliminium ions generated in situ from hydroxylactams is reported. Modest to excellent ee's and yields are obtained in these novel Pictet-Spengler-type reactions with a chiral thiourea-pyrrole catalyst. Useful synthetic transformations of the versatile pyrroloindolizidinone and pyrroloquinolizidinone products are presented.     

Synthesis of thiazolidine-fused heterocycles via exo-mode cyclizations of vinylogous N-acyliminium ions

Syntheses of thiazolidine-fused heterocycles via exo-mode cyclizations of vinylogous N-acyliminium ions incorporating heteroatom-based nucleophiles have been examined and discussed. The formation of (5,6)-membered systems was feasible with all nucleophiles tried (O, S and N), while the closing of the five-membered ring was restricted to O- and S-nucleophiles. The closure of a four-membered ring failed. Instead, the bicyclic (5,6)-membered acetal derivative and the tricyclic system with an eight-membered central ring were obtained from the substrates containing O and S nucleophilic moieties, respectively. The reaction outcome and stereochemistry are rationalized using quantum chemical calculations at B3LYP/6-31G(d) level. The exclusive cis-stereoselectivity in the formation of (5,6)- and (5,5)-membered systems results from thermodynamic control, whereas the formation of the eight-membered ring was kinetically controlled.     

Construction of azacycles based on endo-mode cyclization of allenes

A new procedure for constructing monocyclic five- and six-membered azacycles by the endo-mode ring-closing reaction of allenylazido derivatives under neutral conditions has been developed. The azabicyclo[m.n.0] compounds were prepared by applying this newly developed procedure. The seven-membered azacycle was prepared when the allene possessing an unsubstituted carboxyl amido functionality was submitted to the basic conditions. In addition, indole and quinoline skeletons were synthesized using this procedure.     

Intramolecular Friedel-Crafts-type reactions involving N-acyliminium ions derived from glycine templates

Enantiomerically pure 4-substituted 2-aralkyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones (1b-m) in which the alkyl chain is (CH(2))(n), n = 1-3, behave as glycine templates giving by treatment with [hydroxy(tosyloxy)iodo]benzene in ethyl acetate cis-1-tosyloxy derivatives. When these compounds contain electron-rich aryl substituents with n = 2, they spontaneously cyclize through intramolecular Friedel-Crafts-type diastereoselective reactions to give penta- or hexacyclic compounds. Otherwise, they give by solvolysis cis-1-alkoxy derivatives, which in a second step, may be cyclized in acid if n = 2, 3. All these reactions must occur through N-acyliminium species in S(N)1-like mechanisms. 1-Alkoxy-2-arylmethyl derivatives are reluctant to cyclize, giving trans-1-hydroxy compounds as the only isolated reaction products.     

Synthesis of isoindolo[1,3]benzoxazine derivatives through intramolecular arylation of N-acyliminium ions

[1,3]Benzoxazines annulated to isoindole as 3 and 4 have been synthesized in three steps from N-chloromethylphthalimide 5 and substituted phenols 6 . The key step was the acid-catalyzed cyclization of ω-carbinol lactams 8 and 9.     

Acyclic stereoselection in the reaction of nucleophilic reagents with chiral N-acyliminium ions generated from N-

Optically active N-[1-(phenylsulfonyl)alkyl]imidazolidin-2-ones react at low temperature in the presence of tin tetrachloride to give acyclic N-acyliminium ions. These electrophilic substrates give addition products upon reaction with pi-nucleophiles. Allyltrimethylsilane affords the corresponding allylated products in good yields and high diastereoselectivity. The stereochemical outcome of this process can be rationalized by taking into account the preference of the intermediate N-acyliminium ion for an E configuration that favors the attack of the nucleophile from the si-si face. Disappointing results are obtained using silyl ketene acetals; conversely trimethylsilyl enol ether of acetophenone gives the corresponding adducts in high diastereoselectivity. The utilization of trimethylsilyl enol ether of 2-acetylfuran is particularly interesting since the corresponding adducts are obtained with good diastereoselectivity and the furan ring could be amenable of further synthetic transformations.     

Synthesis of the spirocyclic alkaloid nitramine

The alkaloid nitramine was prepared in a four operation process using reductive cyclization of a γ-cyano ester to a spirolactam as a key step.     

An N-acyliminium cyclization approach to a total synthesis of (+)-cylindricine C

[reaction: see text] Details of problems and solutions encountered during the development of an enantioselective total synthesis of (+)-cylindricine C are described here. The total synthesis itself was accomplished in 8 steps, featuring an N-acyliminium cyclization strategy, the seldom-used Wharton rearrangement, and a key epimerization at C5.     

Diastereoselective, titanium-mediated cyclization of omega-vinyl tethered imides

[reaction: see text] Diastereoselective reductive coupling reactions of omega-vinyl tethered cyclic imides are achieved by a preexisting stereocenter at an allylic position. Particularly noteworthy is the effective use of a 1:2 mixture of Ti(O-i-Pr)4 and n-BuLi to afford the N-acylhemiaminal products in good yields.     

联二烯丁基硫醚衍生物合成呋喃的反应

本文报道以联二烯丁基硫醚为起始物的呋喃衍生物的合成方法.实验结果表明,β-联二烯丁基硫醚醇在氢化钠的作用下以很高的收率环化生成一个苯硫基离去的呋喃产物,β-联二烯丁基硫醚醛与外加亲核试剂作用后能得到多一个取代的类似呋喃产物,而β-联二烯丁基硫醚酮在P2O5的促进下也能环化生成呋喃衍生物.     

First total synthesis of ent-gelsedine via a novel iodide-promoted allene N-acyliminium ion cyclization

The first total synthesis of the oxindole alkaloid gelsedine (1) starting from (S)-malic acid is described. The key step is a novel iodide-promoted intramolecular reaction of an allene with an N-acyliminium ion intermediate which provided in a single step the bicyclic vinyl iodide 11. Other important steps are the highly stereoselective Pd-catalyzed Heck cyclization of N-methylanilide 23a which led to the desired spiro-oxindole 24a, the fully regioselective intramolecular oxymercuration of 25a to the desired cyclic ether, and the remarkable oxindole N-demethylation of 29 via a radical mechanism by using dibenzoyl peroxide. The total synthesis was concluded by the stereoselective introduction of the ethyl group from the bis-Boc compound 41 followed by methoxylation of the oxindole nitrogen. This total synthesis leads to the unnatural (+)-enantiomer of gelsedine in 21 steps and 0.10% overall yield.     

Synthesis of furan from allenic sulfide derivatives

In this paper, we report the synthesis of furan derivatives from allenic sulfides. By the reaction with NaH, β-Hydroxyl allenic sulfides were found to generate furan products in excellent yields with the removal of phenylthio group. β-Aldehyde allenic sulfides were found to give similar furan products with one more substituent when treated with additional nucleophilic reagents. β-ketone allenic sulfides can also cyclize to give furan derivatives with the promotion of P₂O₅.     

Synthesis of 1,3-dioxanes from furan aldehydes

Six new cyclic acetals have been synthesized by the reaction of furfural and its 5-methyl, 5-bromo, 5-chloro, and 5-nitro derivatives and furyl-acrolein with 1,1,1-tris(hydroxymethyl)propane. Their UV and IR spectra are given.     

Synthesis of diarylcyclopropyl spirocyclic ketones

A facile one-pot synthetic route for preparing a series of functionalized diarylcyclopropyl spirocyclic ketones 4 is developed. The efficient cyclopropanation route of the conjugated cyclic ketones 2 with sulfones 1 in the presence of NaH shows interesting molecular diversities. The reaction mechanism of the stereocontrolled cyclopropanations has been discussed.     

N-acyliminium ions: detection of a hidden 2-aza-cope rearrangement

A 2-aza-Cope rearrangement underlying the more typical reactions of N-acyl-2-aza-1,5-hexadienes has been detected using triethylsilane as an acyliminium ion trap.     

Efficient entry to diversely functionalized spirocyclic oxindoles from isatins through carbonyl-addition/cyclization reaction sequences

A novel approach to diversely functionalized spirocyclic oxindoles has been developed by using different metal-mediated carbonyl-addition/cyclization reaction sequences. Spirocyclization precursors, 2-indolinone-tethered homoallylic alcohols, (buta-1,3-dien-2-yl)methanols, and alpha-allenols have been obtained by regioselective addition of stabilized organoindium reagents to isatins in aqueous environment. Ruthenium-, silver-, and palladium-catalyzed reactions of the above unsaturated alcohol derivatives provided oxaspiro oxindoles.