Tandem oxidation processes for the preparation of functionalized cyclopropanes

[reaction: see text] A novel manganese dioxide-mediated tandem oxidation process (TOP) has been developed which allows the direct conversion of allylic alcohols into cyclopropanes, the intermediate aldehydes being trapped in situ with a stabilized sulfur-ylide. This methodology has been applied successfully to a variety of allylic alcohols and to a formal synthesis of the simple, naturally occurring lignan, (+/-)-picropodophyllone.     

The oxidation of organocuprates--an offbeat strategy for synthesis

The creation of carbon-carbon and carbon-heteroatom bonds by the oxidation of organocuprates is useful in a range of challenging contexts including the formation of biaryl bonds within medium rings, diene synthesis and the coupling of tertiary carbon centres. This tutorial review introduces these applications and recent developments which have served to improve its functional group tolerance and its utility in organic synthesis.     

A new strategy for the preparation of maleimide-functionalised gold surfaces

We have developed and investigated a new route to functionalise Au surfaces using maleimide groups. This functionalisation has been performed by grafting aminophenyl (AP) via an electrochemical reduction of 4-aminophenyldiazonium salt in acetonitrile solution and the subsequent chemical binding of N-(2-carboxyethyl) maleimide (NCEM). The resulting maleimide functionalised surface was interacted with a cysteine-modified peptide. The grafting of AP was monitored by the occurrence of NH₂ and aryl ring vibrations, whereas the binding of the NCEM led to a strong and sharp peak because of the C═O stretching mode. The immobilisation of the peptide was identified by the appearance of the amide I band. Half of the maleimide surface groups reacted with the peptide because of steric hindrance. The charge efficiency for the AP layer formation was about 45% at a thickness of about 6–8 nm.     

Studies on the manganese-mediated isomerization of alkynyl carbonyls to allenyl carbonyls

[reaction: see text] A study of the role of base in the isomerization of manganese-coordinated conjugated alkynyl carbonyls to the corresponding allenyl carbonyls is described. The use of phosphine additives indicates that manganese requires a ligand prior to isomerization with amine bases. A series of amine bases were also examined for their efficacy in this isomerization reaction revealing a strong dependence on pK(a). By contrast, potassium tert-butoxide led to rapid isomerization in the absence of added manganese ligand.     

A sulfone-based strategy for the preparation of 2,4-disubstituted furan derivatives

2,4-Disubstituted furans are prepared by treating 2,3-dibromo-1-phenylsulfonyl-1-propene (DBP, 2) with 1,3-diketones under basic conditions. The furan-forming step involves a deacetylation, and the selectivity of this process depends upon the steric demand of the R group. The substituent in position 4 is elaborated by reaction of sulfonyl carbanions with alkyl halides, acyl halides, and aldehydes. Oxidative or reductive desulfonylation produces the 2,4-disubstituted furans in 60-92% yield. This strategy has been used to prepare rabdoketone A (12) and the naturally occurring nematotoxic furoic acid 13.     

A strategy for ready preparation of glycolipids for multivalent presentation

The olefinic residue of n-pentenyl glycosides serves as the trigger for regioselective construction of higher saccharides and then for elaboration in multivalent glycolipids. [reaction: see text]     

Self-assembly strategy for the preparation of polymer-based nanoparticles for drug and gene delivery

Nanoparticulate drug-delivery systems have attained much importance because of their injectable property, the possibility to achieve passive targeting and active targeting, and unique advantages to realize stimuli tailored delivery. Molecular self-assembly is a powerful method for fabricating polymer-based nanoparticles, which involves various driving forces, such as hydrophobic interactions, electrostatic interactions, stereocomplexation, host/guest interactions and hydrogen bonding. By fine tuning one or many types of these interactions, self-assemblies with a wide range of structures and functions could be fabricated. In this article, recent developments in different self-assembly strategies for the preparation of polymer-based nanoparticulate delivery systems are discussed.     

Tandem oxidation processes for the preparation of nitrogen-containing heteroaromatic and heterocyclic compounds

alpha-hydroxy ketones undergo manganese dioxide-mediated oxidation followed by in situ trapping with aromatic or aliphatic 1,2-diamines to give quinoxalines or dihydropyrazines, respectively, in a one-pot procedure which avoids the need to isolate the highly reactive dicarbonyl intermediates. The scope and limitations of these procedures are outlined and modifications to this procedure are discussed in which reduction is carried out in the same reaction vessel, generating piperazines, or oxidation, leading to pyrazines.     

Furan ring oxidation strategy for the synthesis of macrosphelides A and B

By using the convenient protocol for conversion of 2-substituted furans into 4-oxo-2-alkenoic acids ((i) NBS, (ii) NaClO(2)), macrosphelide B (2) was synthesized from furyl alcohol 5 (>98% ee) and acid 6 (99% ee). The protocol was first applied to the PMB ether of 5 to afford acid 13b. On the other hand, DCC condensation of acid 6 with 5 gave 16 after deprotection of the TBS group. Condensation was again carried out between 13b and 16 to furnish the key ketone 17, which upon reduction with Zn(BH(4))(2) afforded anti alcohol 18 stereoselectively (15:1). After protection/deprotection steps, the furan 18 was converted to seco acid 3 by using the furan oxidation protocol mentioned above, and lactonization of 3 with Cl(3)C(6)H(2)COCl, Et(3)N, and DMAP afforded 22 (MOM ether of 2), which upon deprotection with TFA produced 2. Transformation of 22 to macrosphelide A (1) was then investigated. Although the chelation-controlled reduction of 22 should afford the desired anti alcohol 24, Zn(BH(4))(2) at <-90 degrees C gave a 2 approximately 1:1 mixture of anti/syn alcohols. On the contrary, reduction with NaBH(4) in MeOH at -15 degrees C produced the syn isomer 23 with >10:1 diastereoselectivity. Mitsunobu inversion of the resulting C(14)-hydroxyl group and deprotection of the MOM group with TFA afforded 1. Similarly, reduction of 2 with NaBH(4) afforded the C(14)-epimer of 1 stereoselectively. The observed stereoselectivity in the reductions of 22 and 2 could be explained on the basis of computer-assisted calculation, which showed presence of the low-energy conformers responsible for the stereoselective reduction. In addition, conversion of 2 to 1 was established, for the first time.     

Synthesis of termini-differentiated 6-carbon stereotetrads: an alkylative oxidation strategy for preparation of the c21-c26 segment of apoptolidin(1)

[reaction: see text] Two methods have been developed for the synthesis of epoxide 36. The first uses (+)-pulegone 25 as an enantiopure starting material and introduces the requisite intricacy of target 22 in 12 operations. The second method employs an enantiospecific catalytic Jacobsen epoxidation of 1a and is five operations shorter. The second sequence features an oxygen-directed alkylative oxidation reaction that re-establishes the dienyl sulfone functionality with concomitant 1,3-transposition of the sulfone moiety.     

A convenient method for the preparation of fluorous tin derivatives for the fluorous labeling strategy

A convenient method for the preparation of fluorous aryl stannanes was developed as a means of expanding the general utility of the fluorous labeling strategy (FLS). Following the synthesis of a novel fluorous distannane, a palladium-catalyzed cross-coupling reaction was used to prepare the target compounds from aryl halides. The scope of the reaction was investigated by preparing a small library of model compounds where the reaction yields were similar to those reported for the analogous procedures employing hexamethyl- or hexabutyldistannanes. The utility of the reported methodology was demonstrated through the successful synthesis of fluorous precursors to two established molecular imaging and therapy agents (FIAU, IUdR). These were radiolabeled with iodine-125 and the desired products isolated in high yield and effective specific activity.     

A co-activation strategy for enhancing the performance of hematite in photoelectrochemical water oxidation

Hematite(α-Fe_2O_3) is a promising photoanode for photoelectrochemical(PEC) water splitting.However,the severe charge recombination and sluggish water oxidation kinetics extremely limit its use in photohydrogen conversion.Herein,a co-activation strategy is proposed,namely through phosphorus(P)doping and the loading of CoAl-layered double hydroxides(CoAl-LDHs) cocatalysts.Unexpectedly,the integrated system,CoAl-LDHs/P-Fe_2O_3 photoanode,exhibits an outstanding photocurrent density of 1.56 mA/cm~2 at 1.23 V(vs.reversible hydrogen electrode,RHE),under AM 1.5 G,which is 2.6 times of pureα-Fe_2O_3.Systematic studies reveal that the remarkable PEC performance is attributed to accelerated surface OER kinetics and enhanced carrier separation efficiency.This work provides a feasible strategy to enhance the PEC performance of hematite photoanodes.     

A strategy for the synthesis of mesostructured metal oxides with lower oxidation states

A detailed study on the pseudomorphic conversion of ordered mesoporous Co(3)O(4) and ferrihydrite into CoO and Fe(3)O(4), respectively, by using alcohol/water vapor as a gentle reducing agent is described. The reduction conditions for the transformation were optimized. In addition, the first one-pot synthesis of mesostructured CoO by using nanocasting with cubic ordered silica as a hard template is demonstrated.     

Novel strategy for the preparation of 3-perfluoroalkylated-2H-indazole derivatives

A simple and novel methodology for the synthesis of 3-perfluoroalkylated-2H-indazole derivatives has been elaborated. The perfluoroalkylation of readily available 2-nitrobenzaldimines bearing electron donating groups was performed using the Ruppert-Prakash reagent and its analogues to afford α-difluoromethylated, α-trifluoromethylated and α-pentafluoroethylated benzylamines. A final reductive cyclization mediated by SnCl₂·2H₂O led to 2H-indazoles containing perfluoroalkyl groups via the generation of a new NN bond in moderate to good yields.     

A highly selective N-protection strategy for the preparation of 1-N-alkylated kanamycin antibiotics

An O to N acyl migration technique has been used to selectively acetylate the amino groups of the aminosugar rings of kanamycins A and B, leaving the amino groups on the 2-deoxy-streptamine ring unprotected. A formylation-deformylation process then converts these N-acetylated kanamycins to their 3-N-formyl derivatives with high regioselectivity, giving key intermediates for the efficient preparation of 1-N-alkylated kanamycins.