The synthesis of dinaphthothiophenes

The synthesis of dinaphtho[1,2-b:2′,3′-d]thiophene ( 6 ), dinaphtho[2,1-b:2′,3′-d]thiophene ( 15 ), dinaphtho-[1,2-b:1′,2′-d]thiophene ( 20 ), dinaphtho[2,1-b:1′,2′-d]thiophene ( 26 ), dinaphtho[2,3-b:2′,3′-d]thiophene ( 37 ) and dinaphtho[1,2-b:2′,1′-d]thiophene ( 45 ) has been accomplished.     

Facile one-pot synthesis of photochromic pyrans

[reaction: see text]. Photochromic pyrans, including [3H]naphtho[2,1-b]pyrans, [2H]naphtho[1,2-b]pyrans, indeno-fused naphtho[1,2-b]pyrans, and heteroannulated pyrans, were synthesized in excellent yields through a facile one-pot procedure by reaction of propargyl alcohol and naphthol or phenol derivatives in the presence of 5 mol % PPTS and 2 equiv of (MeO)3CH. Symmetrical and nonsymmetrical bispyrans can also be prepared using the protocol.     

Trityl isothiocyanate support for solid-phase synthesis

Trityl isothiocyanate resin [1], prepared from commercially available trityl chloride resin, is a useful precursor of the trityl thiosemicarbazide resin [2]. This resin can be employed in the solid-phase synthesis of a variety of supported isatin beta-thiosemicarbazones [4] and their Mannich derivatives [6]. A variety of thioureas [7] can be easily prepared by the reaction of [1] with amines. The supported thioureas are directly and efficiently converted to 2-aminothiazole-5-carboxylates [8] by reaction with methyl 2-chloroacetoacetate.     

Traceless solid-phase synthesis of heterosteroid framework

[reaction: see text]A traceless solid-phase synthesis of cyclopenta[c]-4H-chromen-8-ol, benzo[d]cyclopenta[e]-3H-3-azin-8-ol, and other 11-heterosteroids via the fulvene hetero [6 + 3] cycloaddition is described.     

Total synthesis of sordaricin

[structure: see text] The total synthesis of sordaricin, the diterpene aglycone of an important class of antifungal compounds, is described. Two approaches were explored, the first of which utilized a possible biogenetic intramolecular [4 + 2] cycloaddition to form the complete carbon skeleton of the target molecule. A second approach using a tandem cycloreversion/intramolecular [4 + 2] cycloaddition sequence is also detailed.     

Diversity-oriented synthesis of azaspirocycles

Multicomponent condensation of N-diphenylphosphinoylimines, alkynes, zirconocene hydrochloride, and diiodomethane provides a rapid access to omega-unsaturated dicyclopropylmethylamines. These novel building blocks are converted into heterocyclic 5-azaspiro[2.4]heptanes, 5-azaspiro-[2.5]octanes, and 5-azaspiro[2.6]nonanes by means of selective ring-closing metathesis, epoxide opening, or reductive amination. The resulting functionalized pyrrolidines, piperidines, and azepines are scaffolds of considerable relevance for chemistry-driven drug discovery.     

艾托拉嗪的合成

自从色洛托宁(Serotonin)在1948年作为神经传导素被发现以后,它就与中枢神经系统(CNS)的活动联系在一起.经过科学家们的多年努力,芳基哌嗪作为种类繁多的5-HT1A受体中的一类得到了迅速发展,像布斯哌隆(Buspirone)和伊沙匹隆((Ipsapirone)很早就作为有效的抗焦虑和抗抑郁症药物得到广泛的应用.     

The synthesis of polycyclic thiophenes derived from phenanthrene intermediates

The synthesis of benzo[b]triphenyleno[2,1-d]thiophene ( 9 ), benzo[b]triphenyleno[1,2-d]thiophene ( 13 ), 5-methylbenz[7,8]anthra[2,1-b]thiophene ( 17 ), l-methylchryseno[3,4-b]thiophene ( 18 ), triphenyleno[1,2-c]dibenzothiophene ( 22 ), triphenyleno[2,1-a]dibenzothiophene ( 26 ), triphenyleno[1,2-a]dibenzothiophene ( 29 ), and triphenyleno[2,1-b]dibenzothiophene ( 30 ) is described.     

Organosilanes in synthesis: application to an enantioselective synthesis of methyl-l-callipeltose

[reaction: see text] Methyl-l-callipeltose, the carbohydrate associated with callipeltoside A, has been synthesized in eight steps and 23% overall yield from enantioenriched allylsilane 6 and acetaldehyde. The key steps are a highly diastereoselective formal [4 + 2] annulation and a Cr(VI)-catalyzed oxidative C-C bond cleavage to produce lactone 11.     

Total synthesis of (+)-sundiversifolide

The first, enantiocontrolled total synthesis of (+)-sundiversifolide has been accomplished using the sequential ring-closing metathesis, [3,3]-sigmatropic rearrangement, and iodolactonization for the key assembly of the cis-fused oxabicyclo[5.3.0]decene framework of the natural product. [structure: see text]     

The Ritter reaction in the synthesis of ortho-fused nitrogen-containing heterocycles

The acid-catalysed condensation of a 1,4- and a 1,5-ditertiary diol with various arylated nitriles is shown to provide a simple and novel route to reduced benz[f]indoles, naphth[1,8a,8-fg]indoles, benzo[4,5]cyclohepta[1,2-b]pyrroles, and benzo[g]quinolines.     

A novel bornane synthesis by an old idea

Aiming at a synthesis of spiro[2.4]hepta-4,6-dienes with a carbon substituent at C-4, we investigated solvolysis reactions of the thiatricycle 2, obtained from spiro[2.4]hepta-4,6-diene (1) and thiophosgene by [4 + 2] cycloaddition. With methanol or ethanol a mixture of the esters 7 and 8 was formed. Desulfurization of the thionoesters 8 gave methyl and ethyl spiro[2.4]hepta-4,6-diene-4-carboxylate (10a,b). The corresponding alcohol (11) was prepared from 10b by LiAlH(4) reduction. Ethenetetracarbonitrile combined with the 4-substituted spiro[2.4]hepta-4,6-dienes to give the [4 + 2] cycloadducts 12a-c. Diels-Alder reaction between 11 and 2-chloroacrylonitrile afforded the spiro(bicyclo[2.2.1]hept-5-ene-7,1'-cyclopropane) derivative 14a that was transformed in three steps to rac-10-hydroxycamphor (17). This synthesis of a bornane derivative opens opportunity for variations and thus may find further applications.     

Radical fluoroarylation in radiochemical synthesis

In this study, we report on the radical [¹⁸F]fluoroarylation of different olefins using 4-[¹⁸F]fluorobenzenediazonium ions to provide a new route to radiopharmaceuticals containing a deactivated, 4-[¹⁸F]fluoro substituted phenyl group. This new methodology was shown to be well suited for the synthesis of ¹⁸F-labelled stilbenes. Stilbene 7 is now accessible within 80 min in 30-45% overall radiochemical yield starting from [¹⁸F]fluoride.     

A cycle for organic nitrile synthesis via dinitrogen cleavage

In the presence of NaH, the reaction between N2 and Mo(N[t-Bu]Ar)3 (Ar = 3,5-C6H3Me2) proceeds at room temperature to afford NMo(N[t-Bu]Ar)3 (95%). Lewis acidic silyl triflates (Me3SiOTf + pyridine or (i-Pr)3SiOTf) mediate a reaction between acid chlorides and NMo(N[t-Bu]Ar)3 to yield acyl imidos [RC(O)NMo(N[t-Bu]Ar)3][OTf] (R = Me, 92%; Ph, 75%; t-Bu, 64%). The reduction of [RC(O)NMo(N[t-Bu]Ar)3][OTf] by magnesium anthracene followed by treatment with Me3SiOTf affords molybdenum ketimides, R(Me3SiO)CNMo(N[t-Bu]Ar)3 (R = Me, 82%; Ph, 77%; t-Bu, 46%). Exposing R(Me3SiO)CNMo(N[t-Bu]Ar)3 to SnCl2 or ZnCl2 produces ClMo(N[t-Bu]Ar)3 (71-93% for SnCl2) and RCN (97-99%). Magnesium metal reduces ClMo(N[t-Bu]Ar)3 to Mo(N[t-Bu]Ar)3 (74%), completing a synthetic cycle. New strategies for the functionalization of sterically hindered nitrides and nitrile extrusion from d2 ketimides are presented in the context of a new route for derivatizing N2.     

Enantioselective synthesis of bridged bicyclic ring systems

The type 2 intramolecular Diels-Alder (IMDA) reaction is a valuable method for synthesis of both carbocyclic and heterocyclic bridged bicyclo[5.3.1]undecane and bicyclo[4.3.1]decane ring systems. These structures are common to a number of biologically important natural products. Asymmetric variants of the type 2 IMDA reaction incorporating oxazolidinone chiral auxiliaries have been evaluated. This study has resulted in systems that deliver bridged bicyclic [5.3.1] and [4.3.1] ring systems in high diastereomeric (97-99% de) and enantiomeric purity.     

Practical synthesis of new functionalized tetraphenylenes

The practical synthesis procedure of substituted tetraphenylene derivatives involving the synthesis of a precursor for 4, 7-dunethoxyisobenzofuran and Diets-Alder addition of 4, 7-dimethoxyisobenzofuran generated in situ to 5, 6, 11,12-te-tradehydrodibenzo[a,e]cyclooctene, followed by a low valent titanium mediated deoxygenation to give 1,4, 11, 14-tetra-methoxy-dibenzo[b, n] tetraphenylene, which can be further demethyiated to the corresponding phenolic compound, which was acetylated to afford 1,4,11,14-tetraacetoxy-dibenzo-[ b, n] tetraphenylene.     

A concise, modular synthesis of chiral peraza-macrocycles using chiral aziridines

[reaction: see text] Novel chiral peraza-macrocycles were synthesized from chiral aziridines as a common building block. Efficient syntheses of chiral [26]-N(6), [12]-N(4), [9]-N(3), and [14]-N(4) systems were accomplished.     

Positive cooperativity in the template-directed synthesis of monodisperse macromolecules

Two series of oligorotaxanes R and R' that contain -CH(2)NH(2)(+)CH(2)- recognition sites in their dumbbell components have been synthesized employing template-directed protocols. [24]Crown-8 rings self-assemble by a clipping strategy around each and every recognition site using equimolar amounts of 2,6-pyridinedicarboxaldehyde and tetraethyleneglycol bis(2-aminophenyl) ether to efficiently provide up to a [20]rotaxane. In the R series, the -NH(2)(+)- recognition sites are separated by trismethylene bridges, whereas in the R' series the spacers are p-phenylene linkers. The underpinning idea here is that in the former series, the recognition sites are strategically positioned 3.5 ? apart from one another so as to facilitate efficient [π···π] stacking between the aromatic residues in contiguous rings in the rotaxanes and consequently, a discrete rigid and rod-like conformation is realized; these noncovalent interactions are absent in the latter series rendering them conformationally flexible/nondiscrete. Although in the R' series, the [3]-, [4]-, [8]-, and [12]rotaxanes were isolated after reaction times of <5-30 min in yields of 72-85%, in the R series, the [3]-, [4]-, [5]-, [8]-, [12]-, [16]-, and [20]rotaxanes were isolated in <5 min to 14 h in 88-98% yields. It follows that while in the R' series the higher order oligorotaxanes are formed in lower yields more rapidly, in the R series, the higher order oligorotaxanes are formed in higher yields more slowly. In the R series, the high percentage yields are sustained throughout, despite the fact that up to 39 components are participating in the template-directed self-assembly process. Simple arithmetic reveals that the conversion efficiency for each imine bond formation peaks at 99.9% in the R series and 99.3% in the R' series. This maintenance of reaction efficiency in the R series can be ascribed to positive cooperativity, that is, when one ring is formed it aids and abets the formation of subsequent rings presumably because of stabilizing extended [π···π] stacking interactions between the arene units. Experiments have been performed wherein the dumbbell is starved of the macrocyclic components, and up to five times more of the fully saturated rotaxane is formed than is predicted based on a purely statistical outcome, providing a clear indication that positive cooperativity is operative. Moreover, it would appear that as the R series is traversed from the [3]- to the [4]- to the [5]rotaxane, the cooperativity becomes increasingly positive. This kind of cooperative behavior is not observed for the analogous oligorotaxanes in the R' series. The conventional bevy of analytical techniques (e.g., HR-MS (ESI) and both (1)H and (13)C NMR spectroscopy) help establish the fact that all the oligorotaxanes are pure and monodisperse. Evidence of efficient [π···π] stacking between contiguous arene units in the rings in the R series is revealed by (1)H NMR spectroscopy. Ion-mobility mass spectrometry performed on the R and R' series yielded the collisional cross sections (CCSs), confirming the rigidity of the R oligorotaxanes and the flexibility of the R' ones. The extended [π···π] stacking interactions are found to be present in the solid-state structures of the [3]- and [4]rotaxanes in the R series and also on the basis of molecular mechanics calculations performed on the entire series of oligomers. The collective data presented herein supports our original design in that the extended [π···π] stacking between contiguous arene units in the rings of the R series of oligorotaxanes facilitate an essentially rigid rod-like conformation with evidence that positive cooperativity improves the efficiency of their formation. This situation stands in sharp contrast to the conformationally flexible R' series where the oligorotaxanes form with no cooperativity.     

Regioselective synthesis of indenols via nickel-catalyzed carbocyclization reaction

2-Halophenyl ketones 1a-e (1a, o-IC(6)H(4)COCH(3)) undergo carbocyclization with alkyl propiolates (2a, CH(3)(CH(2))(4)C[triple bond]CCO(2)CH(3); 2b, TMSC[triple bond]CCO(2)Et 2c, CH(3)C[triple bond]CCO(2)CH(3); 2d, CH(3)OCH(2)C[triple bond]CCO(2)CH(3); 2e, CH(3)(CH(2))(3)C[triple bond]CCO(2)CH(3); 2f, PhC[triple bond]CCO(2)CH(3); and 2g, (CH(3))(3)C[triple bond]CCO(2)CH(3)) in the presence of Ni(dppe)Br(2) and zinc powder in acetonitrile at 80 degrees C to afford the corresponding indenol derivatives 3a-m with remarkable regioselectivity in good to excellent yields. The nickel-catalyzed carbocyclization reaction was successfully extended to other simple disubstituted alkynes. Thus, the reaction of 2-halophenyl ketones 1a-e with disubstituted alkynes (2h, PhC[triple bond]CPh; 2i, CH(3)C(6)H(4)C[triple bond]CC(6)H(4)CH(3); 2j, CH(3)CH(2)C[triple bond]CCH(2)CH(3); 2k, PhC[triple bond]CCH(3); 2l, TMSC[triple bond]CCH(3); and 2m, PhC[triple bond]C(CH(2))(3)CH(3)) proceeded smoothly to afford the corresponding indenols 4a-t in good to excellent yields. For unsymmetrical alkynes 2k-m, the carbocyclization gave two regioisomers with regioselectivities ranging from 1:2 to 1:12 depending on the substituents on the alkyne and on the aromatic ring of halophenyl ketone. A possible mechanism for this nickel-catalyzed carbocyclization reaction is also proposed.     

Parallel solid-phase synthesis of trisubstituted triazinobenzimidazolediones

An efficient method for the solid-phase synthesis of trisubstituted [1,3,5]triazino[1,2-a]benzimidazole-2,4(3H,10H)-diones from resin-bound amino acids is described. N-acylation of the primary amine of a resin-bound amino acid with 4-fluoro-3-nitrobenzoic acid, followed by displacement of the fluoro group and reduction of the nitro group, generated a resin-bound o-dianilino derivative. The dianilino compound was treated with cyanogen bromide to generate the corresponding iminobenzimidazole, which, following treatment with N-(chlorocarbonyl)isocyanate, afforded the resin-bound triazinodione derivative. Alkylation of the triazinodione compound with an alkyl halide yielded, following cleavage of the solid-support, the trisubstituted [1,3,5]triazino[1,2-a]benzimidazole-2,4(3H,10H)-dione.