A tin-complexation strategy for use with diverse acylation methods in the preparation of 1,9-diacyldipyrromethanes

The acylation of dipyrromethanes to form 1,9-diacyldipyrromethanes is an essential step in the rational synthesis of porphyrins. Although several methods for acylation are available, purification is difficult because 1,9-diacyldipyrromethanes typically streak extensively upon chromatography and give amorphous powders upon attempted crystallization. A solution to this problem has been achieved by reacting the 1,9-diacyldipyrromethane with Bu(2)SnCl(2) to give the corresponding dibutyl(5,10-dihydrodipyrrinato)tin(IV) complex. The reaction is selective for dipyrromethanes that bear acyl groups at both the 1- and 9-positions but otherwise is quite tolerant of diverse substituents. The diacyldipyrromethane-tin complexes are stable to air and water, are highly soluble in common organic solvents, crystallize readily, and chromatograph without streaking. Four methods (Friedel-Crafts, Grignard, Vilsmeier, benzoxathiolium salt) were examined for the direct 1,9-diacylation of a dipyrromethane or the 9-acylation of a 1-acyldipyrromethane. In each case, treatment of the crude reaction mixture with Bu(2)SnCl(2) and TEA at room temperature enabled facile isolation of multigram quantities of the 1,9-diacyldipyrromethane-tin complex. The diacyldipyrromethane-tin complexes could be decomplexed with TFA in nearly quantitative yield. Alternatively, use of a diacyldipyrromethane-tin complex in a porphyrin-forming reaction (reduction with NaBH(4), acid-catalyzed condensation with a dipyrromethane, DDQ oxidation) afforded the desired free base porphyrin in yield comparable to that obtained from the uncomplexed diacyldipyrromethane. The acylation/tin-complexation strategy has been applied to a bis(dipyrromethane) and a porphyrin-dipyrromethane. In summary, the tin-complexation strategy has broad scope, is compatible with diverse acylation methods, and greatly facilitates access to 1,9-diacyldipyrromethanes.     

A general strategy for the facile synthesis of 2,7-dibromo-9-heterofluorenes

[reaction: see text] A facile, highly efficient, and economical procedure for the preparation of 6,6'-diiodo-4,4'-dibromo-3,3'-dimethoxylbiphenyl has been found. From this compound, a general synthetic strategy for the preparation of 2,7-dibromo-9-heterofluorenes has been developed. Five 2,7-dibromo-9-heterofluorenes have been easily synthesized for the first time according to the procedure presented, opening the door to new classes of inorganic and organometallic conjugated polymeric materials of polyheterofluorenes.     

A general method for the preparation of 4- and 6-azaindoles

Nitropyridines reacted with an excess of vinyl Grignard reagent to produce 4- or 6-azaindoles. Improved yields were obtained when a halogen atom was present at the position alpha to the nitrogen atom in the pyridine ring.     

A convenient synthesis of 6-, 7-, and 8-membered cyclic phosphodiesters

1,3-, 1,4-, and 1,5-Alkanediols are converted into the corresponding 6-, 7-, and 8- membered cyclic phosphodiesters in a two-step procedure utilizing N-(1,2-dimethylethylene-dioxyphosphoryl)imidazole ($\text{2}\text{?}$ as the sole phosphorylating reagent.     

A general solid phase method for the preparation of diverse azapeptide probes directed against cysteine proteases

[chemical reaction: see text]. A solid phase approach is presented for the synthesis of azapeptide inhibitors and activity based probes (ABPs) for cysteine proteases. This synthetic method allows the incorporation of diverse reactive warheads linked to different peptide recognition elements. Application of this method to the synthesis of a series of caspase probes is described.     

Ring-closing metathesis for the synthesis of novel 9- and 10-membered silicon-containing benzo-fused heterocycles

A ring-closing metathesis (RCM) strategy afforded a number of novel 9- and 10-membered benzo-fused compounds containing at least one silicon atom as part of the heterocyclic portion. In this manner, the following compounds containing heterocyclic rings of 9-10 atoms were synthesized: (Z)-2,2-dimethyl-7-[(4-methylphenyl)sulfonyl]-2,3,6,7-tetrahydrobenzo[h][1,7,2]oxazasilonine, (Z)-2,2-dimethyl-3,6-dihydro-2H-benzo[h][1,7,2]dioxasilonine, (Z)-8-isopropoxy-9-methoxy-3,3-dimethyl-1,3,4,7-tetrahydrobenzo[g][1,2]oxasilonine and (Z)-2,2,7,7-tetramethyl-2,3,6,7-tetrahydrobenzo[i][1,8,2,7]dioxadisilecine.     

A pericyclic cascade to the stereocontrolled synthesis of 9-cis-retinoids

A domino reaction that is pericyclic in nature is thought to be triggered upon treatment of alkenynol 10 with arylsulfenyl chlorides. The process comprises an ordered sequence of sigmatropic rearrangements: a reversible [2,3]-allyl sulfenate to allyl sulfoxide shift, followed by a [2,3]-propargyl sulfenate to allenyl sulfoxide rearrangement, and last a stereodifferentiating [1,5]-sigmatropic hydrogen migration leading to polyene 13. The occurrence of the C7 to C11 hydrogen migration has been demonstrated by labeling experiments. The double diastereoselection of the [1,5]-sigmatropic hydrogen shift to afford a single isomer of the final polyene 13 is thought to arise from a combination of the electronic effect of the sulfoxide at one terminus, and the steric effect imparted by the bulky trimethylcyclohexenyl substituent at the other terminus. The overall process thus constitutes a stereoselective synthesis of an E,Z,Z-triene fragment from an alkenynol and, in particular, a retinoid with the 7E,9Z,11Z,13E configuration on the conjugated polyenic side chain. Application of this method to the synthesis of retinoids, including labeled analogues, is straightforward.     

Nitrenium ion azaspirocyclization-spirodienone cleavage: a new synthetic strategy for the stereocontrolled preparation of highly substituted lactams and N-hydroxy lactams

[reaction: see text] Although 1,4-cyclohexadienes 2, obtained through the Birch reduction of arenes 1, have found widespread use as masked beta-oxo carbonyl synthons 3, the possibility that 2,5-cyclohexadienones 5 might also be employed to the same end has been overlooked despite their ready availability. As part of our ongoing investigation of the synthetic chemistry of nitrenium ions, we have developed a novel and efficient strategy for the stereoselective preparation of di- and trisubstituted azetidinone, pyrrolidinone, and piperidinone derivatives, which features the ozonolytic cleavage of azaspirocyclic 2,5-cyclohexadienones 12. For example, ozonolysis of spirodienone 12c in CH2Cl2 and reductive workup with dimethyl sulfide generated unstable beta-formyl ester 21, whereas cleavage in MeOH followed by reduction with thiourea led to hemiacetal 22. While both 21 and 22 partially decompose upon exposure to silica gel, they can be trapped in situ, with a variety of weakly basic nucleophiles, to usefully substituted products. The requisite spirodienone substrates are readily accessible through the nitrenium ion cyclization of alkyl omega-arylhydroxamates 10, which proceeds with moderate to high diastereoselectivity.     

Synthesis of 6-, 7- and 8-membered cyclosiloxanes having multifunctional groups

Cyclosiloxanes having intramolecular donor atoms, a Si-Si bond, and vinyl groups were synthesized as useful precursors for ring-opening polymerization. 1,1,3,3-Tetrakis(dimethylaminomethylphenyl)-5,5-dimethylcyclotrisiloxane was also synthesized and characterized by single crystal X-ray structural analysis, which shows strong coordination from N to Si in the solid state.     

A general efficient strategy for cis-3a-aryloctahydroindole alkaloids via stereocontrolled ZnBr(2)-catalyzed rearrangement of 2,3-aziridino alcohols

A short and general approach to the cis-3a-aryloctahydroindole alkaloids has been developed on the basis of a key stereocontrolled ZnBr(2)-catalyzed rearrangement of 2,3-aziridino alcohols. Two representative members, (+/-)-crinane and (+/-)-mesembrine, have been synthesized in 15% and 11% overall yields, respectively. [reaction: see text]     

A general strategy to elisabethane diterpenes: stereocontrolled synthesis of elisapterosin B via oxidative cyclization of an elisabethin precursor

Described is an efficient synthesis of the complex bioactive natural product, elisapterosin B, a potent in vitro inhibitor of Mycobacterium tuberculosis H37Rb. The synthesis elisapterosin B, prepared in its enantiomeric form, proceeds by a highly stereocontrolled sequence commencing with a simple glutamic acid derived compound. Pivotal steps in the sequence include (a) a pinacol-type ketal rearrangement to transfer chirality, (b) an IMDA reaction of an E,Z-diene to construct the elisabethin skeleton, and (c) a biosynthesis-inspired oxidative cyclization of the elisabethin precursor to elisapterosin B.     

Palladium-catalyzed disilylation of o-quinodimethanes: synthesis of 9- and 10-membered disilacarbocycles

o-Quinodimethanes are efficiently inserted into a silicon-silicon bond of cyclic disilanes in the presence of a palladium-diphenyl-2-pyridylphosphine catalyst, giving 9- and 10-membered disilacarbocycles, that is, benzodisilonine and benzodisilecine.     

A general strategy for stereoselective glycosylations

The principal challenge that the synthesis of oligosaccharides of biological importance presents is the development of a general approach for the stereoselective introduction of a glycosidic linkage. It is shown here that a (1S)-phenyl-2-(phenylsulfanyl)ethyl moiety at C-2 of a glycosyl donor can perform neighboring group participation to give a quasi-stable anomeric sulfonium ion. Due to steric and electronic factors, the sulfonium ion is formed as a trans-decalin ring system. Displacement of the sulfonium ion by a hydroxyl leads to the stereoselective formation of alpha-glycosides. NMR experiments were employed to show convincingly the presence of the beta-linked sulfonium ion intermediate. The (1S)-phenyl-2-(phenylsulfanyl)ethyl moiety could be introduced by reaction of a sugar alcohol with acetic acid (1S)-phenyl-2-(phenylsulfanyl)ethyl ester in the presence of BF(3)-OEt(2). Furthermore, it could be removed by conversion into acetate by treatment with BF(3)-OEt(2) in acetic anhydride. The introduction as well as the cleavage reaction proceeds through the formation of an intermediate episulfonium ion. The use of the new methodology in combination with traditional neighboring group participation by esters to introduce beta-glycosides makes it possible, for the first time, to synthesize a wide variety of oligosaccharides by routine procedures. The latter was demonstrated by the synthesis of the Galili trisaccharide, which has been identified as an epitope that can trigger acute rejections in xeno-transplantations, by the one-pot two-step glycosylation sequence.     

A general stereocontrolled, convergent synthesis of oligoprenols that parallels the biosynthetic pathway

A solution is reported to the classic unsolved problem of stereoselective synthesis of all-E oligoprenols, such as E-farnesylfarnesol, by a cationic coupling analogous to the biosynthetic pathway. The simplicity and efficacy of the method, which is outlined in Scheme 1, are demonstrated by the synthesis of a series of all-E oligoprenols from C(20) to C(35) in uniformly excellent overall yield. The success of the approach is due not only to the highly E-stereoselective C-C coupling that forms the oligoprenyl chain but also to the development of efficient syntheses of allylic secondary silanes and E-oligoprenal acetals, and to a selective allylic demethoxylation reaction.     

A general method for the preparation of perfluoroalkanesulfonyl chlorides

A mild two-step synthesis of perfluoroalkanesulfonyl chlorides starting from perfluoroalkyl iodides has been developed. Reaction of perfluoroalkyl iodides with sodium dithionite gave sodium perfluoroalkanesulfinate salts which were converted into perfluoroalkanesulfonyl chlorides in 25-73% yield (two steps) using N-chlorosuccinimide.     

A new general method for the preparation of N-sulfonyloxaziridines

[reaction: see text] A simple procedure to obtain N-alkylsulfonyl- and N-arylsulfonyloxaziridines from the corresponding N-sulfinylimines involving a one-pot, two-step oxidation process with m-CPBA (1 equiv) and m-CPBA/KOH (1.1 equiv) is reported. The method is applicable to N-sulfinylimines derived from aldehydes (aliphatic and aromatic) and ketones (dialkyl and aryl alkyl) and preserves C=C-conjugated double bonds. Almost quantitative yields, very mild conditions (usually less than 5 min at room temperature), and easy purification by filtration are the main features of this new procedure, which can be performed at a gram scale.