Diastereoselective construction of azetidin-2-ones by electrochemical intramolecular C-C bond forming reaction

A convenient method for synthesis of optically active azetidin-2-ones using electrochemical oxidation has been exploited. The method consists of a diastereoselective intramolecular C-C bond forming reaction between active methylene and methyne groups through an electrochemical system in which positive iodine species acted as mediators under mild conditions.     

Facile stereoselective synthesis of 1,3-disubstituted-4-trichloromethyl azetidin-2-ones

The highly stereoselective synthesis of 1,3-disubstituted-4-trichloromethyl azetidin-2-ones by the [2+2] cycloaddition of ketenes with imines derived from chloral is described.     

Carbon-carbon bond formation via the electrophilic addition of carbocations to allenes

A novel electrophilic addition of aryl-substituted allenes and carbocations forming a carbon-carbon bond is described. Stereodefined allylic halides and indenes were furnished with excellent regio- and stereoselectivity depending on the structure of allenes.     

Facile diastereoselective synthesis of functionally enriched hydantoins via base-promoted intramolecular amidolysis of C-3 functionalized azetidin-2-ones

Synthesis of functionally enriched hydantoins has been developed and validated via base-assisted intramolecular amidolysis of C-3 functionalized β-lactams.     

Metal-catalysed approaches to amide bond formation

Amongst the many ways of constructing the amide bond, there has been a growing interest in the use of metal-catalysed methods for preparing this important functional group. In this tutorial review, highlights of the recent literature have been presented covering the key areas where metal catalysts have been used in amide bond formation. Acids and esters have been used in coupling reactions with amines, but aldehydes and alcohols have also been used in oxidative couplings. The use of nitriles and oximes as starting materials for amide formation are also emerging areas of interest. The use of carbon monoxide in the transition metal catalysed coupling of amines has led to a powerful methodology for amide bond formation and this is complemented by the addition of an aryl or alkenyl group to an amide typically using palladium or copper catalysts.     

A facile Lewis acid-promoted allylation of azetidin-2-ones

Exposure of 3α-chloro-3-phenylthioazetidin-2-ones and allyltrimethylsilane to a Lewis acid promotes a remarkably facile and stereoselective C-3 allylation to give 3α-allyl-3-phenylthioazetidin-2-ones 4 in excellent yield. These allylated azetidin-2-ones undergo smooth desulphurization with tri-n-butyltin hydride or Raney-nickel producing cis-3-allyl- and cis-3-propylazetidin-2-ones.     

Carbon-carbon bond formation: palladium-catalyzed oxidative cross-coupling of N-tosylhydrazones with allylic alcohols

In the zone: Pd-catalyzed oxidative cross-coupling of N-tosylhydrazones with allylic alcohols leads to C?C bond formation. A palladium-carbene migratory insertion is proposed to play the key role in this transformation. The reaction proceeds with readily available starting materials to afford substituted alkenes in a highly stereoselective manner.     

Carbon-carbon bond formation by radical addition-fragmentation reactions of O-alkylated enols

Alpha-tert-butoxystyrene [H2C=C(OBut)Ph] reacts with alpha-bromocarbonyl or alpha-bromosulfonyl compounds [R1R2C(Br)EWG; EWG =-C(O)X or -S(O2)X] to bring about replacement of the bromine atom by the phenacyl group and give R1R2C(EWG)CH2C(O)Ph. These reactions take place in refluxing benzene or cyclohexane with dilauroyl peroxide or azobis(isobutyronitrile) as initiator and proceed by a radical-chain mechanism that involves addition of the relatively electrophilic radical R1R2(EWG)C* to the styrene. This is followed by beta-scission of the derived alpha-tert-butoxybenzylic adduct radical to give But*, which then abstracts bromine from the organic halide to complete the chain. Alpha-1-adamantoxystyrene reacts similarly with R1R2C(Br)EWG, at higher temperature in refluxing octane using di-tert-amyl peroxide as initiator, and gives phenacylation products in generally higher yields than are obtained using alpha-tert-butoxystyrene. Simple iodoalkanes, which afford relatively nucleophilic alkyl radicals, can also be successfully phenacylated using alpha-1-adamantoxystyrene. O-Alkyl O-(tert-butyldimethylsilyl) ketene acetals H2C=C(OR)OTBS, in which R is a secondary or tertiary alkyl group, react in an analogous fashion with organic halides of the type R1R2C(Br)EWG to give the carboxymethylation products R1R2C(EWG)CH2CO2Me, after conversion of the first-formed silyl ester to the corresponding methyl ester. The silyl ketene acetals also undergo radical-chain reactions with electron-poor alkenes to bring about alkylation-carboxymethylation of the latter. For example, phenyl vinyl sulfone reacts with H2C=C(OBut)OTBS to afford ButCH2CH(SO2Ph)CH2CO2Me via an initial silyl ester. In a more complex chain reaction, involving rapid ring opening of the cyclopropyldimethylcarbinyl radical, the ketene acetal H2C=C(OCMe2C3H5-cyclo)OTBS reacts with two molecules of N-methyl- or N-phenyl-maleimide to bring about [3 + 2] annulation of one molecule of the maleimide, and then to link the bicyclic moiety thus formed to the second molecule of the maleimide via an alkylation-carboxymethylation reaction.     

Carbon-carbon bond formation between alkylated alkenes and acrylic ester via 2-methoxyalkyl radicals

Methoxymercuration/demercuration reactions of alkenes 10 in $\text{10}$ in the presence of acrylic ester yield products $\text{11}$ in a carbon-carbon bond formation reaction.     

Synthetic approaches to Cinchona alkaloids: the C-8/C-9 disconnection strategy

When conducted in DMSO, the Hünig's base-promoted condensation of 3-quinuclidinone with quinoline-4-carboxaldehyde gave an equimolar mixture of epimeric aldols 8 with an excellent yield.     

Carbon-carbon bond formation via a tandem cationic 2-aza-Cope rearrangement-Lewis acid promoted Petasis reaction

Potassium alkynyltrifluoroborates and potassium (2-phenyl)vinyltrifluoroborates react with N-3-butenyl-(2,2-dichloro-1-propylidene)amine in the presence of BF₃·Et₂O as a Lewis acid to synthesize rearranged Mannich products. The reaction starts with a cationic 2-aza-Cope rearrangement of the imine, followed by the Lewis acid promoted borono-Mannich-type reaction on the rearranged imine to result in a new class of functionalized N-homoallylamines.     

Substitution at C-4 in 3,5-disubstituted 4H-1,2,6-thiadiazin-4-ones

3,5-Diaryl-4H-1,2,6-thiadiazin-4-ones react with NaBH₄ to give the 3,5-diaryl-4H-1,2,6-thiadiazin-4-ols and with MeLi to give 4-methyl-3,5-diaryl-4H-1,2,6-thiadiazin-4-ols. The latter dehydrate with p-toluenesulfonic acid to give (3,5-diarylthiadiazin-4-ylidene)methanes. (3,5-Diphenyl-4H-1,2,6-thiadiazin-4-ylidene)methane 15 suffers mono bromination with NBS to give bromo(3,5-diphenyl-4H-1,2,6-thiadiazin-4-ylidene)methane 17. Dichloro- and dibromo(3,5-diphenyl-4H-1,2,6-thiadiazin-4-ylidene)methanes 18 and 19 are formed directly from the 3,5-diphenylthiadiazin-4-one 9 via the Appel reaction using Ph₃P and CCl₄ or CBr₄, respectively. 3,5-Diarylthiadiazin-4-ones treated with P₂S₅ give 3,5-diarylthiadiazine-4-thiones that react with tetracyanoethylene oxide to give the (thiadiazin-4-ylidene)malononitriles. Finally, the 3,5-diphenylthiadiazine-4-thione 20 reacts with ethyl diazoacetate to give ethyl 2-(3,5-diphenyl-4H-1,2,6-thiadiazin-4-ylidene)acetate 26. The above reactions show that a variety of substitutions at C-4 of 3,5-diaryl substituted 1,2,6-thiadiazin-4-ones can be achieved, which extends the potential applications of this heterocycle. All compounds are fully characterized and a brief comparison of their spectroscopic properties is given.     

Nucleophilic reactivity of 1-zirconacyclopent-3-ynes: Carbon-carbon bond formation with aldehydes

Nucleophilic reactions of 1,1-bis(η⁵-cyclopentadienyl)-1-zirconacyclopent-3-yne (1) with proton and aldehydes were studied. The reaction with HCl gave a mixture of 2-butyne and 1,2-butadiene. Complex 1 reacted with benzaldehyde to give 1-phenyl-2-methyl-2,3-butadien-1-ol (3) in moderate yields in the presence of a proton source such as triethylammonium hydrochloride, while it gave 2-methylene-1-phenyl-3-buten-1-ol (4) on using triethylammonium tetraphenylborate.     

Carbon-carbon bond formation of alkenylphosphonates by aldehyde insertion into zirconacycle phosphonates

Ethyl 1-butynylphosphonate reacts with Cp(2)ZrCl(2)/2n-BuLi to give a three-membered zirconacycle that readily inserts aldehydes. Hydrolysis of the intermediate five-membered zirconacycles leads to two products, 4 and 5. In the major product, 5, the aldehyde inserts into C2 of the zirconacycle, while in the minor product, 4, the aldehyde inserts into C1. Products 5 are obtained in 38-75% isolated yields. Products 4 are obtained in approximately 1-12%. Essentially, only compounds 5 are produced with ortho-substituted aldehydes. The regio- and stereochemistry of 4 and 5 were determined by (3)J(PH), (2)J(PC2), and (3)J(PC3) coupling constants.     

Carbon-carbon bond formation reaction of ethereal oxonium ylides via metal-enolate intermediates

First, the carbon-carbon (C-C) bond-forming reaction of aldehydes with bicyclo[m.n.0]-1-oxonium ylides was studied as the ylide was transiently formed in the Rh(II)-catalyzed reaction of a nonenolizable diazoketone, namely, 2-(3-diazo-1,1-dimethyl-2-oxopropyl)-2-methyldioxolane (1). The reaction of 1 with benzaldehyde in the presence of ClTi(Oi-Pr)3 gave the three-carbon, ring-enlarged, and C-C-bonded product 2a (53%). Second, enolizable diazoketone 5 bearing no methyl substituents at the alpha-position was studied under similar catalytic conditions, and the ring-enlarged and C-C-bonded products 19a and 20a were also formed (87%) when titanium compound ClTi(Oi-Pr)3 or Ti(Oi-Pr)4 was used. Similar reactions of diazoketones 27, 29, and 31 bearing a cyclic acetal ring and a longer tethering chain than 5 gave C-C-bonded products 28 (74%), 30 (8%), and 32 and 33 (overall 48%), respectively, albeit 28 and 30 possessed a spiro bisacetal structure. Thus, the hitherto unclarified C-C bond formation of ethereal oxonium ylides with carbonyl electrophiles was realized with the use of an appropriate Lewis acid, for example, ClTi(Oi-Pr)3.     

Carbon-carbon bond formation employing organoiron reagents : Syntheses of lavandulol and red scale pheromone

Some aspects of the chemistry of (η¹-allyl)Fp complexes [Fp =η⁵-C₅H₅Fe(CO)₂] are briefly reviewed, especially the means available for their elaboration. The range of electrophiles which react with (η¹-allyl)Fp complexes has been enlarged to include allyl iodides. Two examples of this reaction are given, the first leading to lavandulol 9, the second providing a short synthesis of the red scale pheromone (R,S-15).