Synthesis and reactivity of cyanomethyl 2‐amino‐4‐methylthiazolyl ketone. A facile synthesis of novel pyrazolo[5,1‐c]1,2,4‐triazine, 1,2,4‐triazolo[5,1‐c]1,2,4‐triazine, 1,2,4‐triazino[4,3‐a]benzimidazole,pyridazine‐6‐imine and 6‐oxopyridazinone derivatives

The novel and versatile cyanomethyl 2‐amino‐4‐methylthiazolyl ketone (5) was prepared by treatment of bromomethyl 2‐amino‐4‐methyl thiazolyl ketone (4) with potassium cyanide. Reaction of 5 with heterocyclic diazonium salts 6a,b and 10 afforded the corresponding hydrazones 7a,b and 11, respectively. Refluxing of the hydrazones in pyridine afforded the corresponding pyrazolo[5,1‐c]‐1,2,4‐triazine, 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine, and 1,2,4‐triazolo[4,3‐a]benzimidazole derivatives 8a,b and 12, respectively, via intramolecular cyclization. Compound 5 coupled also with benzenediazonium chloride to afford the corresponding hydrazone 14, which is an excellent precursor for the synthesis of pyridazine‐6‐imine 17a and pyridazinone 17b. The pyridazine derivatives 17a,b were also prepared by an independent route, that is, the condensation with malononitriles and coupling with benzenediazonium chloride, followed by intramolecular cyclization. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 385–390, 1999     

New 1,2,3‐triazolo[4,5‐d]1,2,4‐triazolo[3,4‐b]pyridazine derivatives II

New tricyclic 1,2,3‐triazolo‐1,2,4‐triazolo‐pyridazine derivatives, bearing a methyl substituent on the 1,2,3‐triazole ring, were prepared as potential biological agents. N‐Methylation of dimethyl 1,2,3‐triazole‐4,5‐dicarboxylate allowed synthesis of the isomeric 1‐methyl‐4,7‐dihydroxy and 2‐methyl‐4,7‐dihydroxy triazolo‐pyridazines 4a and 4b which, by a chlorination reaction, gave the corresponding 1‐methyl‐4‐chloro‐( 6a ), 1‐methyl‐7‐chloro‐ ( 6b ) and 2‐methyl‐4‐chloro‐ ( 9 ) substituted 1,2,3‐triazolo‐pyridazines. The nucle‐ophilic substitution with hydrazine hydrate and the suitable cyclization to form the 1,2,4‐triazole ring, provided the expected tricyclic isomeric derivatives 8a, 8b and 11 respectively. The p‐methoxybenzyl substituent, introduced as a leaving group to obtain either v‐triazolo‐pyridazine or v‐triazolo‐s‐triazolo‐pyri‐dazine derivatives unsubstituted on the 1,2,3‐triazole ring, appeared inadequate. Some compounds underwent binding assays toward the adenosine A₁and A_2A receptors.     

Diazabicycloalkanes with nitrogen atoms in bridgehead positions.

1-Methyl-1-(-haloethyl)-1,2,3,4-tetrahydroquinoxalinium salts were synthesized and the dependence of the hydrolysis and cyclization rate constants on the acidity of the medium and presence of halide was found. It was determined that the monocations of tetrahydroquinoxalines participate in the formation of the benzo[b]-1,4-diazabicyclo[2.2.2]octene system, since blocking the free electron pair of the tertiary nitrogen atom with a methyl substituent significantly accelerates the cyclization and suppresses the hydrolytic side reaction.For Communication 17, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 372–378, March, 1989.     

Conformational analysis of p-tert-butylcalix[4]arene derivatives with trans-alkyl substituents on opposite methylene bridges: destabilization of the cone form by axial alkyl substituents

The stereochemistry of calix[4]arenes substituted by a pair of identical alkyl substituents in a trans fashion at two distal bridges is analyzed. MM3 calculations suggest that increasing the bulk of the alkyl group at the bridges destabilizes those conformations possessing an axial disposition of the substituent. In contrast to the 1,3-dimethyl ether of p-tert-butylcalix[4]arene, which adopts a cone conformation, solution NMR data indicate that the 1,2-alternate conformation is preferred in the dimethyl ether derivatives 5b (alkyl = i-Pr) and 5c (alkyl = t-Bu). In the derivative substituted by the less bulky methyl substituent (5a), both the cone and 1,2-alternate forms coexist in CDCl3. Increasing the polarity of the solvent increases the relative population of the cone form of 5a and 5b. The steric destabilization ensuing from the presence of the axial substituent is so large in the cone conformation of 5c that the 1,2-alternate conformer is the major form even in polar solvents. The cone --> 1,2-alternate interconversion barrier of 5a is 18.2 kcal mol(-1), indicating that the presence of an axial methyl group both destabilizes the cone conformation and decreases its rigidity.     

Reactions of Aromatic S‐ and O‐Enynes with Two Methyl Substituents on the Olefinic Unit Assisted by a Ruthenium Complex: Tandem Cyclization and Product Selectivity

Ruthenium‐assisted cyclizations of two enynes, HC≡CCH(OH)(C₆H₄)X? CH₂CH?CMe₂ (X=S ( 1a ), O ( 1b )), each of which contains two terminal methyl substituents on the olefinic parts, are explored. The reaction of 1a in CH₂Cl₂ gives the vinylidene complex 2a from the first cyclization and two side products, 3a and the carbene complex 4a with a benzothiophene ligand. The same reaction in the presence of HBF₄ affords 4a exclusively. Air oxidation of 4a in the presence of Et₃N readily gives an aldehyde product. In MeOH, tandem cyclizations of 1a generate a mixture of the benzothiochromene compound 10a and the carbene complex 7a also with a benzothiochromene ligand. First, cyclization of 1b likewise proceeds in CH₂Cl₂ to give 2b . Tandem cyclization of 1b in MeOH yields comparable products 10b and 7b with benzochromene moieties, yet with no other side product. The reaction of [Ru]Cl with HC≡CCH(OH)(C₆H₄)S? CH₂CH?CH₂ ( 1c ), which contains no methyl substituent in the olefinic part, in MeOH gives the carbene complex 15c with an unsubstituted thiochromene by means of a C? S bond formation. Structures of 3a and 15c are confirmed by X‐ray diffraction analysis. The presence of methyl groups of enynes 1a and 1b promotes sequential cyclization reactions that involve C? C bond formation through carbocationic species.     

Fischer cyclization of 5-substituted pyrid-2-yl-hydrazones of cyclohexanone

The effect has been studied of the nature of the substituent (methyl, chloro, nitro group) on the Fischer cyclization of 5-substituted pyrid-2-yl-hydrazones of cyclohexanone under the action of different catalysts: Lewis acids and strong mineral and arylsulfonic acids.     

新型苯并咪唑衍生物的合成及其抗凝血活性

以3-［(3-氨基-4-甲基氨基苯甲酰)吡啶-2-基氨基］丙酸乙酯为原料,与4-氰基-3-氟苯取代基乙酸经环化反应制得3-【【2-｛［(4-氰基-3-氟苯取代基）甲基］-1-甲基-1-H-苯并咪唑-5-基｝羰基】吡啶-2-基】氨基丙酸乙酯（3a, 3e）; 3经水解和酰胺化反应制得3-【【【2-｛［(4-氰基-3-氟苯基)取代基］甲基｝-1-甲基-1H-苯并咪唑-5-基】羰基】吡啶-2-基氨基】丙酰取代胺基（6a~6h）;6与乙酰氧肟酸经环合反应合成了8个新型的苯并咪唑衍生物（7a~7h）,其结构经1H NMR和HR-ESI-MS表征。抗凝血活性结果表明： 7a和7c的抗凝血活性最好,其aPTT值分别为(83.1±4.2) s和(80.7±2.9) s,优于阳性对照药达比加群酯(75.3±2.1)s。     

Synthesis and cytotoxic activity of benzophenanthrolinone analogues of acronycine

Condensation of either 2-bromobenzoic acid (4) or 2-chloro-3-nitrobenzoic acid (5) with suitable aminoquinolines 6-8 afforded phenylquinolylamines 9-13. Acid mediated cyclization gave the corresponding 12H-benzo[b][1,7]phenanthrolin-7-ones 14 and 15, and 12H-benzo[b][1,10]phenanthrolin-7-ones 16-18. Compounds 14, 16, and 17 were subsequently N-methylated to 6-demethoxyacronycine and acronycine analogues 19-21, whereas reduction of the aromatic nitro group of 18 gave the amino derivative 22. Unsubstituted 12H-benzo[b][1,10]phenanthrolin-7-ones 16, 17, 20, and 21 were devoid of significant cytotoxic activity, whereas 18 and 22, bearing a nitrogen substituent at position 11, were significantly active. Unsubstituted 12H-benzo[b][1,7]phenanthrolin-7-ones 14 and 19, which include a pyridine nitrogen in the same 4-position as the pyran oxygen of acronycine exhibited cytotoxic activities within the same range of magnitude as acronycine itself.     

Tautomeric equilibrium between penta- and hexacoordinate silicon chelates. A chloride bridge between two pentacoordinate silicons.

The reaction of O-trimethylsilyl-1,1-dimethyl-2-trifluoroacetylhydrazine (1a) with chloromethyl(methyl)dichlorosilane affords an unexpected equilibrium mixture, 10a right arrow over left arrow 11a, between a neutral hexacoordinate silicon chelate with a covalent chloro ligand (10a) and an ionic pentacoordinate silicon complex (11a). The equilibrium reaction consists formally of a migration of the covalent chloro ligand from silicon to an adjacent ammonium nitrogen, as a chloride anion, and thus constitutes a novel type of tautomeric reaction. Crystallographic and NMR data provide evidence for the reaction. Temperature, solvent, substituent, and counterion effects on the tautomeric equilibrium are discussed: when the temperature of the mixture is raised, the equilibrium ratio 10a/11a increases. Formation of the mixture in toluene, a nonionizing solvent, shifts the equilibrium completely toward the neutral 10a. When the initial hydrazide has a phenyl (11c) or a hydrogen (11b) group as substituent, rather than CF3, the equilibrium is shifted to the ionic side. Replacement of the chloride counterion by triflate, using trimethylsilyl triflate, shifts the 10a/11a mixture to the ionic side. Low-temperature NMR monitoring of the stepwise formation of 10/11 was carried out and provided insight into the reaction mechanism. In an attempt to grow crystals of 11c, the pentacoordinate tautomer analogue, an unprecedented chloride-bridged disiloxane complex, with two pentacoordinate silicons sharing a common axial chloro ligand, crystallized and was characterized and described.     

Enantioselective total synthesis of (-)-triptolide, (-)-triptonide, (+)-triptophenolide, and (+)-triptoquinonide

The first enantioselective total synthesis of (-)-triptolide (1), (-)-triptonide (2), (+)-triptophenolide (3), and (+)-triptoquinonide (4) was completed. The key step involves lanthanide triflate-catalyzed oxidative radical cyclization of (+)-8-phenylmenthyl ester 30 mediated by Mn(OAc)3, providing intermediate 31 with good chemical yield (77%) and excellent diastereoselectivity (dr 38:1). (+)-Triptophenolide methyl ether (5) was then prepared in > 99% enantiomeric excess (> 99% ee), and readily converted to natural products 1-4. In addition, transition state models were proposed to explain the opposite chiral induction observed in the oxidative radical cyclization reactions of chiral beta-keto esters 17 (without an alpha-substituent) and 17a (with an alpha-chloro substituent).     

N─苯基邻苯二甲酰亚胺和N─对甲苯基邻苯二甲酰亚胺的晶体和分子结构

报道一种新类型的有机电子晶体Ｎ－苯基邻苯二甲酰亚胺（１）（Ｃ＿（１４）Ｈ＿９ＮＯ＿２）和Ｎ－对甲苯基邻苯二甲酰亚胺（２）（Ｃ＿（１５）Ｈ＿（１１）ＮＯ＿２）的晶体和分子结构，（１）属正交晶系，空间群为Ｐｃａｂ，ａ＝７．６４９（４），ｂ＝１１．６５９（２），ｃ＝２３．７３９（３）Ａ，Ｖ＝２１１７．０Ａ￣３，Ｚ＝８，Ｄ＿ｃ＝１．４０１ｇ／ｃｍ￣３，Ｍ＿ｒ＝２２３．２３，μ＝０．８８５ｃｍ￣（－１），最终偏离因子Ｒ＝０．０５３，Ｒ＿ω＝０．０４８；（２）属正交晶系，空间群为Ｐｎａ２＿１，ａ＝７．６２４（２），ｂ＝１１．２３７（１），ｃ＝１３．８５６（２）Ａ，Ｖ＝１１８７．０　Ａ３，Ｚ＝４，Ｄ＿ｃ＝１．３２８ｇ／ｃｍ￣３，Ｍｒ＝２３７．２６，μ＝２．７６４ｃｍ－１，最终偏离因子Ｒ＝０．０３６，Ｒ＿ω＝０．０３２。晶体结构测定结果表明，邻苯二甲酰亚胺的内酰亚胺碳、氮、氧原子与其苯并环共平面。化合物（２）中的甲基碳原子与取代基苯环共平面，苯并酰亚胺平面与取代苯环平面间的夹角分别为５８．４°（化合物１）和５６．２°（化合物２）。     

Diastereoselective approach to 11-aryl steroid skeletons through a cobalt(I)-mediated [2+2+2] cyclization of allenediynes

The cobalt(I)-mediated [2+2+2] cycloaddition reactions of allenediynes of yne-allene-yne type bearing an aryl group on the allene are described. The cyclizations are totally chemo- and regioselective and show low diastereoselectivities. η⁴-Complexed tricyclic (6,6,6) compounds were obtained in good yields as mixtures of endo/exo diastereomers. The cyclization is also compatible with an oxyfunctionality at C3. By designing an allenediyne having a preexisting D ring, we succeeded in building skeletons of 11-aryl steroids in one step and in a totally diastereoselective manner and with simultaneous introduction of an angular methyl group at C10 and an aryl substituent at C11.     

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.     

"Dimers" and "trimers" of tetrahydroindenes and hexahydroazulenes, respectively generated from [2-(1-cycloalkenyl)ethynyl]carbene complexes (M = W, Cr) by cascade cyclization/cycloaddition reactions

A cascade of cyclization/cycloaddition reactions was triggered by addition of protic oxygen nucleophiles ROH 2 (RO = CH3CO2, PhCO2, PhO) to [2-(1-cyclohexenyl)ethynyl]carbene complexes 1b and 1c (M=W, Cr, respectively), affording highly strained "dimers" 11/11' and "trimers" 12 of the carbene ligand. The first reaction step involved the formation of 1-metalla1,3,5-hexatrienes 7, which readily gave tetrahydroindenes 8 by pi cyclization and extrusion of the metal unit. "Dimers" 11/11' were generated from tetrahydroindenes 8 by a highly exo selective [4+2] cycloaddition of compounds 1b and 1c to afford 1-metalla-1,3,5-hexatriene intermediates 9, and a spontaneous pi cyclization of the latter compounds involving the disengagement of the metal unit. Propenylidene cyclohexenes 13/13' were formed in "ene"-type side reactions to the pi cyclization of 1-metalla-1,3,5-hexatrienes 7, by loss of the metal unit. "Dimers" 11 were transformed into "trimers" 12 by a [4+2] cycloaddition and subsequent pi-cyclization of the resulting 1-metalla-1,3,5-hexatriene system. The course of the reaction was elucidated by means of model reactions with (2-phenylethynyl)carbene complex 14, in which 1-metalla-1,3,5-hexatriene intermediates 16 and 17 were isolated and characterized. Alkynyl benzene derivatives 19 were obtained by an unprecedented ring-expansion of a cyclopentadiene unit of "dimers" 11a and 11c, involving the insertion of a carbene carbon atom of compound 14 into a C=C bond. A reaction cascade leading to "dimers" 24/24' could also be triggered by treatment of compounds 2 with [2-(1-cycloheptenyl)ethynyl]carbene tungsten complex 1d.     

Diastereocontrol in open-chain nucleophilic attack on a double bond adjacent to a stereogenic centre carrying a silyl group

The bis[dimethyl(phenyl)silyl]cuprate reagent introduces a silyl group to the beta-position of three alpha,beta-unsaturated esters: methyl Z-4-dimethyl(phenyl)silylpent-2-enoate 11, and methyl Z- and E-(1'-dimethylphenylsilylbenzyl)but-2-enoates 14 and 15, diastereoselectively in the unexpected sense, syn to the silyl group in the conformation in which the hydrogen atom is 'inside'. The selectivity is low (58:42) in the first case 11, where the nucleophilic attack is adjacent to the stereogenic centre carrying the silyl group, and moderate (72:28) for both Z- and E-alpha,beta-unsaturated esters 14 and 15, where the nucleophilic attack is at the other end of the double bond from the stereogenic centre. It is conceivable that nucleophilic attack actually takes place in a conformation in which the donor substituent, the silicon-carbon bond, is out of conjugation with the double bond.     

Preparation and properties of centrally bridgehead-substituted hexacyclo[4.4.0.02,1.03,5.04,8.07,9]decanes ("diademanes") and related (CH)10 hydrocarbons

6-Trimethylsilyl- (1 b), 6-hydroxymethyl- (1 e), and 6-methyldiademane (1 f) have been prepared by irradiation of the corresponding snoutene derivatives, in 23, 2.8, and 17 % yields, respectively, together with the isomeric 1-trimethylsilyl- (10 b) and 1-methyldiademane (10 f) (8 and 2 % yields, respectively). The starting 4-trimethylsilyl- (9 b) and 4-(trimethylsilyloxymethyl)snoutene (9 d) were prepared from the correspondingly substituted cyclooctatetraenes 4 b and 4 c in several steps in 20 and 8 % overall yields, respectively. Upon heating, as well as under the conditions of gas-chromatographic separation, diademanes 1 b, 10 b, 1 f, and 10 f rearranged into the corresponding C10- and C1-substituted triquinacenes 3 b, 3 f, 11 b, and 11 f, respectively. Rough kinetic measurements of these rearrangements indicate some acceleration of the reaction caused by the presence of a methyl substituent and retardation by that of a trimethylsilyl substituent, relative to the parent diademane 1 a. At this insufficient precision, however, the activation energies (E(a)) of 29.0 and 28.1 kcal mol(-1), respectively, are essentially the same as that reported for 1 a (28.3 kcal mol(-1)). An X-ray crystal structure analysis of trimethylsilylsnoutene 9 b revealed a significant lengthening of the distal (with respect to the substituent) bond (1.534 versus 1.505 A) in the unsubstituted cyclopropane ring. In the substituted cyclopropane ring, the two proximal bonds are lengthened (1.530 A) and the distal bond is slightly shortened 1.492 A). This indicates a small, but significant electron-withdrawing effect of the trimethylsilyl group in 9 b. An X-ray crystal structure analysis of 6-hydroxymethyldiademane 1 e showed pronounced alternation of the bond lengths in the six-membered ring, with 1.494(4) between and 1.539(4) A within the three cyclopropane moieties, in close agreement with computations at different theoretical levels. This structural feature corroborates a predisposition of the tris-sigma-homobenzene skeleton of this molecule in the ground state to undergo the facile [sigma(2)(s) + sigma(2)(s) + sigma(2)(s)] cycloreversion to the triquinacene skeleton observed for the parent diademane 1 a, its derivative 1 b and 1 f, as well as for other tris-sigma-homobenzene derivatives.     

A general strategy for the synthesis of vincamajine-related indole alkaloids: stereocontrolled total synthesis of (+)-dehydrovoachalotine, (-)-vincamajinine, and (-)-11-methoxy-17-epivincamajine as well as the related quebrachidine diol, vincamajine diol, and vincarinol

[structures: see text] The highly convergent stereocontrolled total synthesis of (-)-vincamajinine (7), (-)-11-methoxy-17-epivincamajine (9), and the oxygen-bridged (+)-dehydrovoachalotine (22) are described. Key steps in the synthesis of 7 and 9 involved the stereospecific enolate-driven palladium-catalyzed cross-coupling reaction, a Tollens reaction, an acid-assisted intramolecular cyclization to form the C(7)-C(17) quaternary center, and two stereospecific reductions. The efficiency of this strategy is illustrated by the completion of the synthesis of 7 and 9 in 16 [from d-(+)-tryptophan methyl ester 17] and 17 (from the Sch?llkopf chiral auxiliary 27) reaction vessels, respectively. This constitutes the first total synthesis of these indole alkaloids and provides the first regiospecific route to 11-methoxy-substituted ajmaline/vincamajine-related alkaloids. The synthesis of 22 required a novel DDQ-mediated cyclization to furnish the C(6)-O(17) bond, executed in stereospecific fashion. Completion of these syntheses illustrates a concise and versatile strategy for the synthesis of vincamajine-related alkaloids, which has also been employed to prepare the related compounds quebrachidine diol (53), vincamajine diol (56), and vincarinol (59).     

Synthesis of N‐methyl‐4‐pyridyl‐1,2,3,4‐tetrahydroisoquinolines via a pictet‐spengler cyclisation

The synthesis of N‐methyl‐4‐pyridyl‐1,2,3,4‐tetrahydroisoquinolines (6a,b,c) was achieved via a Pictet‐Spengler cyclization of an activated amino group derivatized in a carbamate form. The obtained compounds have been designed as potential serotonin analogs.     

Axial and Equatorial Substitution of Dimethylamine on Phosphorus in the 1,3,2-Oxazaphosphorinane Ring System: Structures of 2-Dimethylamino-Phenyl-2H-1,3,2-oxazaphosphorinane-2-Oxides

X-ray structures of trans-2-dimethylamino-5-phenyl-2H-1,3,2-oxazaphosphorinane-2-oxide, 5b , and trans-2-dimethylamino-6-phenyl-2H-1,3,2-oxazaphosphorinane-2-oxide, 6c , have been determined. These two compounds have been prepared in a straightforward manner by a reaction of cyclization of Mc₂NP(O)Cl₂ with the corresponding 3-amino-2-phenylpropanol and 3-amino-1-phenylpropanol, respectively, to produce (5b, 6b) and (5c, 6c) , and were separated into pure forms by chromatography. Crystal data of 5b : space group P_ccn, a = 10.675(5), b = 31.685(9), c = 7.217(3) Å, R = 0.065 for 1040 reflections. Crystal data of 6c: space group P-1, a = 9.803(6), b = 12.455(5), c = 12.690(2) Å, α = 114.11(2), β = 80.88(2), γ = 111.64(4)°, R = 0.035 for 3534 reflections. For the pair 5b and 6b , the slowly-migrating 5b is trans (Ph and P = O group trans) with the configuration of 2RS, 5RS, hence 6b is the cis isomer. For the pair 5c and 6c , the slowly migrating 6c is trans with the configuration of 2RS, 6SR; hence 5c is the cis isomer. In both X-ray structures the 1,3,2-oxazaphosphorinane rings are chair-like with the P-end essentially flattened. With a conformationally demanding 5-phenyl substituent, 5b has an axial Me₂N whereas with also a conformationally demanding 6-phenyl substituent, 6c has an equatorial Me₂N. For 6c , the exocyclic P-N bond has partial double bond character: the geometry about exocyclic N is planar. On the other hand, for 5b , the geometry about exocyclic N deviates considerably from planarity, the sum of the angles around N being 343.3°. In the crystalline state, the two crystallographically independent molecules of 6c are linked together in a hydrogen-bonded system involving the water molecule.     

Asymmetric synthesis of 2,3-dihydrofurans and of unsaturated bicyclic tetrahydrofurans through alpha-elimination and migratory cyclization of silyloxy alkenyl aminosulfoxonium salts. Generation and intramolecular O,Si-bond insertion of chiral disubstituted beta-silyloxy alkylidene carbenes

Treatment of the bis(allylsulfoximine)titanium complexes derived from the beta-methyl-substituted acyclic allylic sulfoximines 13a and 13b with aldehydes gave with high selectivities the corresponding sulfoximine-substituted homoallylic alcohols which were isolated as the silyl ethers 15a-h. Methylation of sulfoximines 15a-h afforded the aminosulfoxonium salts 5a-h which upon treatment with LiN(H)tBu gave in high yields the enantio- and diastereomerically pure silyl-substituted 2,3-dihydrofurans 4a-h. Treatment of the titanium complexes derived from the cyclic allylic sulfoximines 17a, 17b, and ent-17c with p-MeOC(6)H(4)CHO delivered with high selectivities the corresponding sulfoximine-substituted cyclic homoallylic alcohols which were isolated as the silyl ethers 18a, 18b, and ent-18c, respectively. Methylation of sulfoximines 18a, 18b, and ent-18c furnished the aminosulfoxonium salts 8a, 8b, and ent-8c, respectively, whose treatment with LiN(H)t-Bu gave the enantio- and diastereomerically pure fused bicyclic 2,3-dihydrofurans 6a, 6b, and ent-6c, respectively, in good yields. It is proposed that the 1-alkenyl aminosulfoxonium salts 5a-h, 8a, 8b, and ent-8c react with the base under alpha-elimination and formation of the acyclic and cyclic beta-silyloxy alkylidene carbenes 2a-h, 7a, 7b, and ent-7c, respectively, which then undergo a 1,5-O,Si-bond insertion and 1,2-silyl migration. The cyclic aminosulfoxonium salts 8a, 8b, and ent-8c upon treatment with 1,8-diazabicyclo[5.4.0]-7-undecene did not undergo an alpha-elimination but suffered a novel migratory cyclization with formation of the enantio- and diastereomerically pure bicyclic tetrahydrofurans 9a, 9b, and ent-9c, respectively. It is proposed that the 1-alkenyl sulfoxonium salts 8a, 8b, and ent-8c are isomerized to the allylic aminosulfoxonium salts 10a, 10b, and ent-10c, respectively, which then suffer an intramolecular substitution of the (dimethylamino)sulfoxonium group by the silyloxy group followed by a desilylation. The syntheses of the 2,3-dihydrofurans 4a-h, 6a, and 6b and of the tetrahydrofurans 9a and 9b are accompanied by the formation of sulfinamide 16 of >or=98% ee, which can be converted via sulfoxide 28 of >or=98% to the starting sulfoximine 11 of >or=98% ee.