Search

The first asymmetric [2,3]-sigmatropic rearrangement of achiral allylic amines has been realized by quaternization of the amines with an enantiomerically pure diazaborolidine and subsequent treatment with Et3N. The resultant homoallylic amines were obtained in good yields and excellent ee's. The observed diastereo- and enantioselectivities were rationalized by invoking a kinetically controlled process, and support for this model was obtained from an NMR spectroscopic investigation of the chiral Lewis acid-substrate complex. The structure of the Lewis acid-product complex was established by X-ray crystallographic analysis and supported the proposed mechanism.

A new type of Rh2(OAc)4-catalyzed [2,3]-sigmatropic rearrangement of sulfur ylides is reported. A series of cyclopropenes were successfully employed for [2,3]-sigmatropic rearrangement by a reaction with either allylic or propargylic sulfides. Under the optimized conditions, the reaction afforded the products in moderate to excellent yields. In these transformations, the vinyl metal carbenes generated in situ from the cyclopropenes were effectively trapped by sulfides, resulting in the formation of corresponding products upon [2,3]-sigmatropic rearrangements.

Electrophilic trifluoromethylthiolation of allylic alcohols with N-trifluoromethylthiosaccharin (Shen′s reagent) affords the corresponding allylic trifluoromethanesulfenates, which spontaneously rearrange into trifluoromethyl sulfoxides.

The highly diastereoselective base-promoted intramolecular cyclization of a variety of enantiopure sulfinyl dienyl amines provides novel sulfinyl tetrahydropyridines that are readily converted to 3-hydroxy tetrahydropyridines via sigmatropic rearrangement. The influence of N- and C- substituents on the process has been studied. Procedures to shorten the sequence such as the tandem cyclization followed by [2,3]-sigmatropic rearrangement, as well as cyclization of the free amine, under Boc- or ArSO- deprotection conditions have been examined. Good to excellent levels of selectivity are generally observed for the reported transformations (dr: 75/25 to >98/2). A novel protocol to access substituted amino dienyl sulfoxides is also reported., This research was supported by MINECO (CTQ2013-46459- C2-2-P) and (CTQ2009-07752) cofunded by FEDER. We also thank CSIC for a contract to RHB (201080E101) and CSIC and Fondo Social Europeo for a JAE-doc contract to CS. LI thanks Comunidad de Madrid (Spain) for support (BIPEDD-2: S2010-BMD-2457). We are grateful to Dr. Carmen de la Torre (IQOG-CSIC) and Dr. Miguel Ángel Sierra (UCM) for encouragement and support.

The applied catalyst (zeolite Ag-USY) can be recycled several times and therefore this reaction becomes “greener”.

Two new approaches to the synthesis of sulfonyl‐functionalized allenecarboxylates and phosphorylated allenes are described. 2‐Sulfonyl‐alka‐2,3‐dienoates were readily prepared in an one‐pot reaction by [2,3]‐sigmatropic rearrangement of sulfinato‐substituted 2‐alkynoates, in situ generated from ethyl propynoate and subsequent treatment with lithium diisopropyl (LDA), ketone, trimethylchlorosilane (TMSCl), and the corresponding sulfinyl chlorides. Preparation of 1‐sulfonyl‐alka‐1,2‐dienephosphonates and ‐1,2‐dienyl phosphine oxides consists of the reaction of the lithio compounds, in situ generated from phosphorylated allenes and LDA, with the corresponding sulfonyl chlorides.

The Rh(I)-catalyzed Pauson–Khand reaction of allenynes afforded the bicyclo[6.3.0]undecadienones as well as their benzo and furo derivatives. In addition, a novel [RhCl(CO)2]2-catalyzed [2,3]-sigmatropic rearrangement of the sulfinic ester species of propargyl alcohols was developed.

The first examples of sigmatropic rearrangements of ene-endo-spirocyclic, tetrahydropyridine-derived ammonium ylids are reported. Thus, spiro[6.7]-ylids rearrange primarily by a [2,3]-pathway, whereas the analogous [6.6]-ylids rearrange by [1,2]- and [2,3]-mechanisms in roughly equal proportions. This method serves as a rapid entry to the core of a range of alkaloids bearing a pyrrolo[1,2-a]azepine or octahydroindolizidine nucleus.

Sigmatropic rearrangement has been utilized for stereoselective syntheses of structurally complicated natural products because of its high stereoselectivity and reactivity. Quinic acid (1) and its ...

Furans and benzofurans of type 1 were dearomatized via the [2,3]-Still–Wittig rearrangement. Enol ethers 2 could be isolated or isomerized to the corresponding furans 3 . The substitution pattern at the homofuranylic position had a strong influence on reaction behavior. Benzofurans rearranged with the greatest efficiency, and employment of a 3-substituted benzofuran ( 1 ; R′=CH 3 ) allowed the creation of a quaternary carbon center.

A ring-contractive and highly diastereoselective [2,3]-sigmatropic rearrangement occurs when N-methyl-1,2,3,6-tetrahydropyridine is treated with sub-stoichiometric amounts of copper or rhodium salts, in the presence of ethyl diazoacetate, giving ethyl cis-N-methyl-3-ethenyl proline (4).

Catalytic asymmetric [2,3] sigmatropic rearrangement of sulfur ylides generated from aryldiazoacetates and propargyl sulfides with a number of chiral Rh(II) and Cu(I) catalysts have been investigated and moderately high enantioselectivities (up to 81% ee) have been achieved.

An investigation of the Lewis acid mediated [2,3]-sigmatropic rearrangement of allylic ammonium ylides has been conducted by employing various bases and boron Lewis acids. Using BBr3 together with ...

The tandem sulfonium ylide formation-[2,3]-sigmatropic rearrangement reaction of chiral non-racemic secondary allylic sulfides, (E)-9 and (Z)-10, is found to proceed with high diastereocontrol. The C-5 stereocenter bearing the sulfide group is essential for high diastereoselectivity in the reaction. Transition state conformers are proposed to explain the high diastereoselectivity in the formation of the diastereomeric products, 18a and 18b. The method is applied to the synthesis of (R)-4-(4-chlorophenyl)-2-butyrolactone. Modest enantioselectivity (63% ee) was achieved and this is attributed to partial racemization during the formation of the secondary allylic sulfide 22.

The intermediate 6 can be converted into enone 13 using a [2.3]sigmatropic sulfoxide rearrangement as the key transformation. The C-13 hydroxylation of 13 was studied, and found to give 14 (epimeric to guanacastepene A). Examination of silyl enol ethers of 13 demonstrated the ready isomerization of the kinetic silyl enol ether into the more stable thermodynamic silyl enol ether under mild electrophilic reaction conditions.

The hitherto unreported 3-aryloxyacetyl-6-methyl-2,3-dihydrothieno[3,2- c ]pyran-4-ones were synthesized in 62–71% yield by the sulfoxide rearrangement of 4-(4′-aryloxybut-2′-ynylthio)-6-methyl-2-pyrone. The substrates were synthesized by phase-transfer-catalysed alkylation of the hitherto unreported 4-mercapto-6-methylpyran-2-one.

The rearrangement of a range of N-benzyl-O-allylhydroxylamines to the corresponding N-allylhydroxylamines upon treatment with n-BuLi in THF, followed by reduction to the corresponding N-allylamines, is described. Mechanistic studies of the transformation are consistent with an intramolecular [2,3] sigmatropic rearrangement.

A convenient method is described for the synthesis of isolevoglucosenone 5, via allylic selenide 3, and its rearrangement to allylic alcohol 4, followed by oxidation with manganese oxide. Isolevoglucosenone 5, is produced in 62% overall yield.

A number of 3-(4′-aryloxybut-2′-ynyl)thio-5,5-dimethyl cyclohex-2-enones are synthesized in 80–90% yield by phase transfer catalyzed reaction of 5,5-dimethyl-3-merca-ptocyclohex-2-enone with a number of 1-aryloxy-4-chlorobut-2-ynes. The sulfides are oxidized with 1 equiv. of m -chloroperoxybenzoic acid and the resulting sulfoxides are then stirred at r.t. for 6–8 h to give 2-aryloxymethyl-3-( m -chlorobenzoyloxy)-6,6-dimethyl-5,6,7-trihydro benzo( b )thiophene-4-ones in 70–80% yield.

The scope of the NCS-mediated amination/[2,3]-sigmatropic rearrangement of enantioenriched allylic selenides is expanded to provide access to the product classes listed in title.

The scope of the NCS-mediated amination/[2,3]-sigmatropic rearrangement of enantioenriched allylic selenides has been expanded to provide access to three new product classes. The use of N-protected amino acid amides provides a novel strategy for accessing peptide chains containing unnatural vinyl glycine amino acid residues. Also reported is the use of amino acid esters, allowing the diastereoselective synthesis of N,N-dicarboxymethylamines, a motif found in a number of pharmaceuticals. Furthermore, use of a range of N-aromatic and N-heteroaromatic amines allows the formation of enantioenriched N-arylamino acids, a motif found in a number of synthetically and biologically interesting compounds.

A convenient protocol is developed for the denitrogenative [2,3] sigmatropic rearrangement of triazoles with allyl sulfides and benzylphenyl sulfide.

The synthetic value of this procedure is demonstrated by total synthesis of racemic kumausallene (VI) starting from a mixture of IIc and IIIc.

This paper describes the first examples of catalyst-dependent asymmetric induction in the periselective [2,3]-sigmatropic rearrangement of propargylic oxonium ylides generated by catalytic diazo decomposition. Catalysis of α-diazo-s-keto esters 4a—g using dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate] in toluene has led to the virtually exclusive formation of benzofuran-3-ones bearing an allenic group with up to 79% ee.

Our results on an enantioselective and diastereoselective oxidation (up to 89% ee) and imidation (up to 87% ee) of organic selenides to afford optically active selenoxides and selenimides, respectively, which lead to optically active organic compounds by succesive selenoxide elimination or [2,3]sigmatropic rearrangement, are mainly described.

A stereospecific [2,3] sigmatropic rearrangement of functionalized bi- or tricyclic allylic sulfoxides and selenoxides as a route to new allylic alcohols and their transformation into the corresponding α-hydroxy ketones having a defined stereochemistry is described. It has been demonstrated that cycloadducts, derived from [4+2] cycloaddition of (Z)-1-alkylthio-2-diethoxyphosphoryloxy-1,3-dienes to a various dienophiles, are versatile synthons carrying much structural and stereochemical information.

The tandem ylide generation and rearrangement or cycloaddition sequence triggered by copper (I) or dirhodium (II) complex-catalyzed decomposition of α-diazo carbonyl compounds has recently found numerous applications in organic synthesis. While exceptionally high levels of enantiocontrol in C-H insertions and cyclopropanations have already been achieved using welldesigned chiral metal catalysts, the development of an enantioselective version of this process has not been so straightforward as it was believed until several years ago that the reactions of ylides would occur from the free ylide detached from the catalyst rather than from the metal complexassociated ylide. The rapid recent developments in this area reviewed here have shown that high levels of asymmetric induction are possible with rearrangements of oxonium ylides and with 1, 3-dipolar cycloadditions of carbonyl ylides where the chiral metal catalyst can remain bound to the ylides in the product-forming step.

The reaction of a series of ketones with dimsylsodium in dimethyl sulfoxide resulting in the formation of γ-unsaturated thiols was studied experimentally. [2,3]-Sigmatropic rearrangements of β-unsaturated sulfinyl carbanions are involved at the key step of those transformations. DFT computations at the B3LYP/6-31+G* level indicated that such rearrangements, as well as some typical [2,3]-sigmatropic rearrangements, e.g., thermal rearrangements of allyl sulfoxides and Wittig rearrangements of sulfur ylides and lithiated allyloxy methyl anions, are concerted and moderately synchronous processes. Negative (diatropic) nucleus-independent chemical shifts (NICS) and high diamagnetic susceptibility exaltations indicate that the transition structures of these [2,3]-sigmatropic migrations are aromatic.

Trimethylsilyldiazomethane reacts with allylic sulfides in the presence of catalytic quantities of Rh2(OAc)4 (1 mol%) to give homoallylic sulfides in good yields and with high diastereoselectivity.

The preparation of several 2,4-diyne-l,6-diols and their esterification with trichloromethanesulfenyl chloride is described. The thus generated bis-propargylic trichloromethanesulfenates undergo spontaneous double [2,3]-sigmatropic rearrangement which leads to the formation of conjugated diallenic trichloromethyl sulfoxides in good to excellent yields.

Trimethylsilyldiazomethane is compared with ethyl diazoacetate for the rhodium, copper, and cobalt catalyzed formation and [2,3] rearrangement of allylsulfonium ylides. At room temperature, the reaction can be carried out using the allyl sulfide as the limiting reagent by slow addition of 3 equivalents of the diazo compound. Slightly better yields were obtained with trimethylsilyldiazomethane than with ethyl diazoacetate.

This paper describes the use of selenium-based [2,3] sigmatropic rearrangement in combination with ruthenium-catalyzed ring-closing metathesis (RCM) for the synthesis of azaspiro ring systems, as exemplified by the reactions of model substrates 5 and 6 . The methodology has been applied to a short and efficient formal total synthesis of the alkaloid (±)-perhydrohistrionicotoxin ( 2 ). Thus, (±)-depentylperhydrohistrionicotoxin, 1 , a known key intermediate for the synthesis of 2 , was synthesised from 2,3-epoxycyclohexan-1-one in 10 laboratory operations and ca. 20% overall yield. The synthetic route is potentially enantioselective, and key steps were the [2,3] sigmatropic rearrangement of 11 to 12 via the corresponding allylic selenide (86% yield) and ruthenium-catalyzed RCM of 13 to 14 (80%).

Reduction of aryl and vinyl radicals to the corresponding organosamarium species by SmI2 can be attained by using benzene-HMPA as a solvent system. Thus, SmI2-mediated Barbier- and Grignardtype coupling reactions between ketones and aryl, vinyl, or alkynyl iodides proceed via organosamarium species in benzene-HMPA. Reductive dehalogenation of 1, 1-dihaloalkenes by SmI2 in benzene-HMPA generates alkylidenecarbenes, which undergo either 1, 5-C-H insertion giving cyclopentenes or 1, 2-shift giving alkynes. On the other hand, SmI2 was found to be useful to effect 2, 3-rearrangement under mild conditions. Metalated ethers undergoing Wittig rearrangement are regioselectively generated by either an intramolecular 1, 5-hydrogen transfer of a vinyl radical, generated by a single electron transfer from SmI2 to γ-haloallyl ethers, or a net two-electron reduction of diallyl acetals with the liberation of an allyloxy samarium by SmI2 in acetonitrile. 2, 3-Rearrangement of allylic sulfonium ylides can be effected by the reaction of allylic sulfides with samarium carbenoid, generated from CH2I2 and SmI2 in THF.

An efficient approach to the enantioselective synthesis of a series of amino acids from either bromoacetyl bromide or glycine is described using a [2,3]-sigmatropic rearrangement to establish the stereogenic centre at C-2 under mild conditions. Protected allylglycine 5 is a valuable building block to several amino acids e.g. hydrolytic cleavage of the auxiliary in 5 followed by deprotection gave L-allylglycine in 92% yield whilst oxidative cleavage of the terminal alkene followed by deprotection gave L-aspartic acid in 67% yield over the 2 steps. Furthermore alkene 5 may be converted to hydroxy ester 8 which is an intermediate for the synthesis of various amino acids including L-lysine and L-proline. Since the enantiomer of sultam 1 is commercially available, the analogous D-amino acids may be synthesised. This chemistry is readily adapted for the incorporation of isotopic labels for example for the synthesis of [1,2- 13 C 2 , 15 N]-L-homoserine 14.

1,3,4,5,6,11a-Hexahydro-7E-2-benzothionine 5, which is a [2,3] sigmatropic rearrangement product of 2-phenyltetrahydrothiopyranium 1-methylide 8, has been synthesized by reaction of 1-methyl-2-phenyltetrahydrothiopyranium triflate 3 with sodium amide in liquid ammonia or by the fluoride ion-induced desilylation of trans-2-phenyl-1-[(trimethylsilyl)methyl]tetrahydrothiopyranium perchlorate trans-7. Compound 5 is stable at room temperature and reverts to ylide 8 by ring-opening.

Oxonium ylide [2,3] sigmatropic rearrangement of trans-divinyl ethylene oxide is observed upon its exposure to ethyl or t-butyl diazoacetate in the presence of either Rh(II) or Cu(II) catalysts to produce cis-6-vinyl-3,6-dihydropyran-2-carboxylates.

The first synthesis of optically pure selenuranes 1 has been accomplished by utilizing 2-exo-hydroxy-10-bornyl group as a chiral ligand. Complete retention of the configuration has been observed in alkaline hydrolysis of 1 to give selenoxides 2. The structure of 1 and 2 has been fully established by X-ray crystallography. [2,3] Sigmatropic rearrangement of allylic selenoxides 2 gave the corresponding allylic alcohols 3 with up to 88% enantiomeric excess (ee). The [2,3] sigmatropic rearrangement of allylic selenoxides 2 progresses predominantly via an endo transition state.

The formation of 13-membered ring oxonium ylides and their subsequent stereocontrolled [2,3]-sigmatropic rearrangement to 10-membered ring lactones occurs in catalyst dependent competition with macrocylic cyclopropanation.

Several new chiral rhodium(II) catalysts have been synthesised for evaluation as catalysts in asymmetric oxonium ylide-[2,3] sigmatropic rearrangement of diazocarbonyl substrates; a catalyst derived from (S)-tert-leucine afforded a chiral benzofuranone derivative with an ee of 60 %.

Allyl aryl sulfides and diazoacetic acid esters react in the presence of optically active Co(III)-salen complex (4) with good enantioselectivity, to give the [2,3]sigmatropic rearrangement products, 2-arylthio-3-aryl-4-pentenoic acid esters, via the corresponding S-ylides.

Tricyclic benzothiazepinium salts (5) were prepared by [2+ +4] polar cycloaddition of thionium intermediates (4A), generated from corresponding α-chloro sulfides (4) and dienes in the presence of silver perchlorate. X-Ray analysis of 5a revealed that the configuration of the thiazepinone skeleton and the dihydrothiopyran ring is cis-fused.Reactions of benzothiazepinium salts (5) with NaBH4 or NaH afforded 3, 6-epithiobenzazocinone derivatives (9) in high yields by [2, 3]-sigmatropic rearrangement of an ylide intermediate (11). The stereochemistry of epithiobenzazocinone (9a) was determined by the nuclear Overhauser enhancement (NOE) technique and finally by X-ray analysis of the sulfoxide (10) derived from epithiobenzazocinone (9a) by m-chloroperbenzoic acid (MCPBA) oxidation. Alkylation of epithiobenzazocinone (9a) afforded 3-alkyl-3, 6-epithiobenzazocinones (12) with retention of the configuration at C-3. Dihydrothiopyran derivatives (13) were obtained in good yields by SmI2 reduction of benzothiazepinium salts (5).

A rearrangement reaction in which a carbon–heteroatom bond migrates to form a new carbon–carbon bond is a powerful tool in organic synthesis. Rearrangement reactions have been widely used as key steps in the synthesis of complex organic structures. In this chapter, the [1,2]- and [2,3]-rearrangements of ylides, the [2,3]-Wittig and the aza-[2,3]-Wittig rearrangements, and the [3,3]-sigmatropic rearrangement are discussed, including some mechanistic aspects followed by some pertinent examples of their application in stereoselective synthesis. Keywords: reorganization of skeleton; sigmatropic rearrangement; CC bond formation; stereoselective synthesis; [1,2]-Stevens rearrangement; [2,3]-sigmatropic rearrangement; ylide; stereocenter; Claisen rearrangement; Cope rearrangement; Ireland-Claisen; Johnson Claisen; aza-Claisen; aza-Cope; [2,3]-Wittig rearrangement; aza-[2,3]-Wittig rearrangement; [3,3]-sigmatropic rearrangement; organic synthesis; total synthesis

Cycloadditions reactions are very efficient tools for the constructions of multiple bonds in one step and are therefore methods of choice for the total synthesis of natural products and drugs. The use of a terminal nitrogen containing partner allows for the stereoselective formations of a CN bond. Because of the vast number of nitrogen containing compounds available, this field has found a widespread interest in total synthesis. This chapter will cover the cycloadditions in which a CN bond is formed. It will be devoted to the description of [2+2], [3+2], [3+3], [4+2], and [2+2+2] processes that are key steps in total synthesis with imine, nitroso, azo, isocyanate, azomethine imine, azide, or azadiene reagents. A discussion of regioselectivity, diastereoselectivity, and enantioselectivity issues will be provided for each reaction. Keywords: cycloaddition; stereoselective; CN bond formation; total synthesis; drug; natural product; imine; nitroso; azo; isocyanate; azomethine imine; azide; azadiene; lactam; pharmaceutical; regioselective; N -heterocycle; Staudinger cycloaddition; Curtius rearrangement; [2,3]-sigmatropic rearrangement; nitroso-Diels-Alder reaction; azo-Diels-Alder reaction; heteroaromatic ring

Chemical building blocks: ?-Sulfenylated imines containing a quaternary center, an ubiquitous subunit and excellent building block, were achieved by rhodium-catalyzed denitrogenative [2,3] sigmatropic rearrangements of N-sulfonyl-1,2,3-triazoles with allylaryl(alkyl) sulfides. Coupling of this methodology with a copper-catalyzed cycloaddition reaction provides a platform for the direct regioselective functionalization of alkynes (see scheme; TC=thiophenecarboxylate; Ts=p-toluenesulfonyl). � 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reaction of carbenoids with propargylic alcohols results in tandem oxonium ylide formation/[2,3]-sigmatropic rearrangement to yield allenes with high enantioselectivity.

Two vicinal stereogenic centers are generated in the title reaction with excellent enantioselectivity.

The [2,3] sigmatropic rearrangement of allylic nitroxides and sulfoxides was studied by ab initio methods. The geometries of the reactants and the transition structures are generated by using RHF/3-21G∗, RHF/6-31+G∗, and MP2/6-31+G∗ theoretical models. The energies were evaluated by single MP3/6-31+G∗ and MP4/6-31+G∗ single point calculations on MP2/6-31+G∗ geometries. The results of this study showed that the allylic sulfoxides are more reactive than allylic nitroxides and that the major product of allyl sulfoxide rearrangement will be formed from the endo transition structure.

The rhodium(II)-catalyzed cyclization of acyclic α-diazo-β-keto esters 1c,d provided stereoselectively the highly substituted cyclohexanones 3c,d respectively, by the [2,3]sigmatropic rearrangement via stereocontrolled nine-membered allylsulfonium ylides 2c,d. Further elaboration of 3d toward the cyclohexanone 36 accomplished asymmetric formal syntheses of the representative elemanoids, 37 and 38. The compound 3c was transformed into the cyclohexanone 34a and cyclohexene 43, which could serve as the key intermediates for the synthesis of natural products possessing contigously cis-arranged trimethylcyclohexanone and its related moieties, respectively.