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A novel [gamma]-selective conjugate addition of 1-silyl-substituted dienol ethers to nitroalkenes activated by Lewis acids is developed. The resulting [alpha],[beta]-unsaturated acylsilanes have undergone photoinduced protodesilylation to produce the corresponding enals, which is transformed into azepanes under appropriate reductive conditions.

The sequential rhodium-catalyzed silycarbocyclization followed by palladium-catalyzed cross-coupling reactions is described to synthesize functionalized cyclopentanes with a highly substituted exocyclic double bond. The reaction that involved 1,6-enynes and underwent silylcarbocyclization, found that if the enyne bears an electron-deficient double bond then the major side reaction, silyformation, can be suppressed by carrying out reaction under a substochiometric amount of CO.

A variety of achiral Lewis bases are found to catalyze the addition of TMSCN to the aldehydes. Among them, phosphines and amines are the most efficient catalysts and in addition several chiral amines and phosphines are examined in a catalytic, asymmetric addition of TMSCN to benzaldehyde albeit with low enantioselecitivity.

The mechanism of the catalytic, enantioselective addition of trichlorosiyl enolates to aldehydes is investigated. Determination of Arhenius activation parameter revealed that aldol addition occurs through the reversible albeit unfavorable formation of an activated complex, and natural-abundance (sup.13C) NMR kinetic isotope effect (KIE) studies have determined that the turnover limiting step is the aldol addition.

The consequences of double diastereodifferentiation in chiral Lewis base catalyzed aldol additions using chiral enoxysilanes derived from lactate, 3-hydroxyisobutyrate, and 3-hydroxybutyrate was investigated. Trichlorosilyl enolates derived from the chiral methyl and ethyl ketones were subject to aldolization in the presence of phosphoramides, and the intrinsic selectivity of these enolates and the external stereoinduction from chiral catalyst was studied.

The mechanism of the phosphoramide-catalyzed enantioselective aldol additions of trichlorosilyl enolate 1 to aldehydes is studied. The mechanism of the Lewis base-catalysed enantio-selective crossed-aldol reactions of aldehydes is proposed to involve three fundamental steps like ionization of chloride, binding of the aldehyde to the cationic silicon species and aldolization.

Chiral phosphoramide-catalyzed aldol reactions of the TMS enol ether derived from acetaldehyde with aromatic aldehydes that provides aldol products in high yield and enantioselectivity is discussed. The aldol products obtained in these cases were of R configuration.

The generality of catalytic, enantioselective alpha-additions of isocyanides to aldehydes is demonstrated. The rate of addition of the isocyanide is found to be crucial for good yields and high selectivities.

The catalytic enantioselective addition of an acetate enolate equivalent to ketones is described. The results show that methyl trichlorosilyl ketene acetal reacts with a wide range of ketones in the presence of pyridine N-oxide to afford the aldol addition products in excellent yields.

A [3 + 2] cycloaddition reaction between alkynyldimethylsilyl ethers and aryl and alkyl nitrile oxides to produce isoxazolylsilanols is developed. The cross-coupling reactions of these heterocyclic silanols with a variety of aryl iodides afford 3,4,5-trisubstituted isaxazoles.

The synthesis of (+)-brasilenyne has been described. The C(8) stereogenic center was set by a reagent-controlled asymmetric allylboration.

Research has been conducted on the chital fluoro ketones. The preparation of these ketones has been carried out in examining their potential as enantioselective catalysts for the asymmetric epoxidation with Oxone and the details are described.

This article presents a de novo synthesis of a pyrrolizidine alkaloid 1-epiaustraline using the tandem [4+2]/[3+2] nitroalkene cycloaddtion method. Results reveal that the complete synthesis involves 10 steps with an overall yield of 7%.

Research has been conducted on the bisoxazoline. The structural variation of this bisoxazoline at the C(4) stereogenic center has been investigated and the results indicate that the bulkier groups give enhanced stereoselectivity.

The synthesis of (--)-7-epiaustraline and (--)-1-epicastanospermine uses a common intermediate and involves an extension of the tandem [4+2]/[3+2] cycloaddition protocol, which includes alkylation in the hydrogenolysis step. The yields are 23% and 20%, respectively

The synthetic route of (+)-casuarine follows a tandem [4+2]/[3+2] nitroalkene cycloaddition involving nitrobenzoate, chiral vinyl ether, and vinyl silane and the intermolecular [3+2] dipolar cycloadditons of nitronates. The yield is 20%.

A study was conducted to analyze the preparation of different chlorosilyl enolates from esters, thiol esters, acylsilanes, and ketones. Experimental results indicated the generality of the preparation of chlorosilyl enolates of esters and ketones through the silicon-tin metathesis reaction. Findings also showed that the use of trichlorosilyl triflate as a trichlorosilylating reagent supported the utilization of methathetical reactions.

A study was conducted to analyze the 1,4-syn diastereoselective, phosphoramide-catalyzed aldol additions of chiral methyl ketone enolates. Configuration assignments were based on an X-ray crystal structure of aldol adducts. Methyllithium was added dropwise to a cold solution of (S)-methyl 2-((dimethyl(1,1-dimethylethyl)silyl)oxy)proponate. Results indicated the compatibility of trichlorosilyl enolate/phosphoramide with common protecting groups.

The simplest nitroalkene, nitroethylene, was observed to undergo Lewis-acid-promoted (4 + 2) cycloaddition with chiral vinyl ethers to produce cyclic nitronates with high diastereoselectivity. The resulting cyclic nitronates were found to react with electron deficient alkenes to produce a face selective (3 + 2) cycloaddition. Stereocontrol in the (3 + 2) cycloaddition was due to a single ring substituent, a remote acetal center.

A new variant of the tandem inter [4 + 2]/intra [3 + 2] nitroalkene cycloaddition has been developed. Intermolecular [4 + 2] cycloaddition of a 2-nitroalkene (bearing an unsaturated ester moiety, the dipolarophile) with a vinyl ether produces a cyclic nitronate substituted at C(3) wherein the only stereogenic center is the anomeric carbon C(6). Since the dipolarophile is attached to a tether extending from the C(3) of the nitronate ([Alpha]-carbon of the nitroalkene), the intramolecular [3 + 2] cycloaddition affords a spiro tricyclic nitroso acetal. The cycloaddition proceeds smoothly for three- and four-atom tethers to afford five- and six-membered rings. Both E- and Z-unsaturated esters serve well as dipolarophiles, but the E-isomers react more selectively. Hydrogenolysis of the nitroso acetals affords the spiro tricyclic [Alpha]-hydroxy lactams in good yield. Remarkably high levels of asymmetric induction are observed with the use of a chiral vinyl ether derived from (1R, 2S)-2phenylcyclohexanol. The origin of asymmetric induction is a combination of the established face selectivity of the enol ether and the preference for a distal fold of the tether away from the substituent on the anomeric carbon. The scope and limitations of this transformation and an analysis of the origin of stereoselectivity are provided.

The feasibility of the bridged (alpha-tether) mode of the tandem inter[4+2]/intra[3+2] cycloaddition was investigated. It was found that simple 1,4-pentadienes and 2-alkoxy-1,4-pentadienes function effectively as dienophile and diporophile combinations with excellent chemical selectivity and regio- and diastereoselectivities. Chiral 2-alkoxy-1,4-pentadienes were observed to undergo the tandem process with excellent asymmetric induction.

The presence of zinc iodide during the catalytic enantioselective cyclopropanation of allylic alcohols enhanced the reaction rates in bis-methanesulfonamide. The effects of zinc iodide on the bis-methanesulfonamide-catalyzed reaction of allylic alcohols in the presence of bis(iodomethyl)zinc reagents were mediated by reagent modification via a Schenk equilibrium. Furthermore, the presence of zinc iodide induced the formation of a highly reactive (iodomethyl)zinc iodide.

A series of bis(oxazoline)palladium complexes was synthesized from the reaction of oxamide with amino alcohols. The resulting amides were chlorinated with thionyl chloride to form the 2,2'-bis(oxazoline)ligands via base-promoted cyclization. The 2,2'-bis(oxazoline)palladium complexes were also utilized as catalysts for the synthesis of palladium chelates and novel carbon-bound complexes via diazomethane-based cyclopropanation.

The seven-step synthesis of enantiomerically pure (-)-mesembrine from 2,2-disubstituted 1-nitroalkene is described. The key step in the synthesis is the tandem inter (4 + 2)/intra (3 + 2) cycloaddition of a 2,2-disubstituted alkene and a chiral vinyl ether derived from (1R,2S)-2-(1-methyl-1-phenylethyl)cyclohexanol to form the octahydroindole framework of the target compound. The conditions and mechanisms for the reactions are presented.

The 10-step synthesis of (-)-detoxinine from the commercially available dicholorodiisopropylsilane is described. The scheme involves the asymmetric tandem inter (4 + 2)/intra (3 + 2) cycloaddition between silyoxynitroalkene and chiral vinyl ether. The method showed the exceptional diastereoselectivity provided by the temporary silicon tether in the tandem nitroalkene cycloaddition reaction.

The cyclopropanation agent, bis(iodomethyl)zinc, was utilized for the catalytic, enantioselective cyclopropanation of a series of allylic alcohols and a homoallylic alcohol. The rapid enantioselective cyclopropanation of allylic alcohols was dependent on the ethyl zinc alkoxide of the allylic alcohol which acts as a substrate. Furthermore, the formation of a zinc complex and the addition of zinc iodide were also vital for rapid and selective cyclopropanation.

(+)-Crotanecine (1), the necine base component of a number of pyrrolizidine alkaloids, was synthesized in 10 steps and 10.2% overall yield. The primary step in the asymmetric synthesis is a Lewis acid-promoted, tandem inter(4 + 2)/intra(3 + 2) cycloaddition between a (fumaroyloxy)nitroalkene 14 and chiral beta-silylvinyl ether (-)-26. This synthesis demonstrates the synthetic versatility of the tandem cycloaddition to incorporate additional functionality.

Ab initio calculations concerning the potential energy surface of phosphoryl (PC) bond rotation in the 2-oxo and 2-thioxo-2-methyl-1,3,2-diazaphosphorinane and -1,3,2-diazaphospholidine anions were performed at different levels of theory to determine the relationship between reactivity and structure of phosphorus(V)-stabilized carbanions. The results, which were validated via NMR and x-ray crystallographic experiments, showed differences in the N-substituent orientation response of the ring system to P-C bond rotation between the oxo and thioxo derivatives.

A new synthetic path to (-)-rosmarinecine from a fumaroyl acid chloride is described. The procedure affords the necine base portion of the pyrrolizidine alkaloid (-)-rosmarinine in eight steps and 14.8% yield. Its critical step is a Lewis acid-catalyzed reaction, namely, tandem inter(4 + 2)/intra(3 + 2) cycloaddition between a fumaroyloxy nitroalkene and a chiral vinyl ether.

Tandem reactions are transformations that result in complex systems with increased synthetic efficiency. Cascade or domino reactions and multicomponent cyclizations are examples of tandem reactions. This review focuses on tandem cascade cycloadditions of nitroalkenes for the construction of highly functionalized nitrogen-containing heterocycles. The discussion also includes tandem [4+2]/[3+2] cycloadditions involving other functional groups.

The chiral, phosphoryl- and thiophosphoryl-stabilized carbanions undergo stereoselective alkylations. The alkylation of carbanions from 2-thioxo-1,3,2-oxazaphosphorinanes proceed diastereoselectively for both the isomers. Diastereoselective alkylation is observed for the P-methoxymethyl analog derived anions in the presence of HMPA or PMDTA. The alkylation selectivity is higher for P-ethylthiophosphonamidates compared to the respective 2-oxo analogs.

The asymmetric Michael addition reaction of chirally modified P-allyl ions with cyclic enones has been examined. The phosphorus stabilized anions were derived from enantiomerically enriched 2-allyl-1,3,2-oxazaphosphorinane 2-oxides. The racemic oxide has been found to be extremely diastereomeric in the Michael addition to 5-, 6- and 7-ring enones. Anions derived from the trans series were highly regio- and diastereoselective (90% diastereomeric excess) while those from the trans series were not diastereoseletive (less than 10% diastereomeric excess).

An ab initio study shows that the activation barrier for P-C bond rotation in P-methylthioxophosphonic diamide anion (8-) is higher than that found in previous oxophosphoryl analog studies on the phosphoryl analog 7-. The result indicates that the stabilizing capabilities of the different chalcogens are different. The study is conducted on structures and energies of different rotamers of 8- compared to 7-. Details of analysis of phosphoryl- and thiophosphoryl-stabilized anions are given.

The amino alcohols and malonyl dichloride derivatives, either natural or synthesized, are used for the synthesis of a set of enantiomerically pure 4-substituted bisoxazolines. The first step in the synthesis involves the formation of bis-amides of the malonyl derivatives with the amino alcohols. Then, the hydroxy amides undergo cyclization by either heating with thionyl chloride in toluene or by first generating the bismesylate followed by heating with aqueous or alcoholic base. This reaction mechanism is effective for producing bisoxazolines constituting bulky substituents at C-4.

Studies have shown that chiral vinyl and propenyl ethers derived from (R)-2,2-diphenylcyclopentanol are more effective compared to other chiral auxiliaries. The chiral auxiliary can be easily prepared in three steps from commercially available starting materials using an asymmetric, oxazaborolidine-catalyzed borane reduction of the corresponding ketone. Several synthetic and mechanistic aspects of the auxiliary are discussed.

A study was conducted on the extension of the two-step cycloaddition/hydrogenolysis process to the general and enantioselective synthesis of 3-substituted and 3,4-disubstituted pyrrolidines. The new protocol employed simple 2-substituted 1-nitroalkenes and easily-prepared chiral, vinyl ethers derived from (R)-2,2-diphenylcyclopentanol and (1R,2S)-2-phenylcyclohexanol. The approach is being eyed for the synthesis of natural and non-natural pyrrolidines as well.

A new, simple procedure enables the catalytic epoxidation of nine olefins to the corresponding epoxides in 83-96% yield. Use of phase transfer catalysts containing a carboxyl group helps generate dioxiranes, which epoxidizes different alkenes. Optimization studies suggest potassium monoperoxosulfate as an efficient oxidant, and help determine reaction conditions to optimize epoxidation yields.

An exocyclic 2,2-disubstituted-1-nitroalkene results from Heck cyclization of an iodoaryl in the presence of triphenylphosphine, Pd(OAc)2 and Ag2CO3 in benzene with a Pd catalyst. Selenylation, oxidative elimination and olefin isomerization of the nitroalkane side product result in a 70% yield of the desired nitroalkene. An arylpalladium intermediate is obtained during this reaction, for which the presence of Ag2CO3 is crucial.

A six-step, asymmetric synthesis of the pyrrolizidine necine base (-)-hastanecine involves a vital reaction of sequential inter(4 + 2)/inter(3 + 2)nitroalkene cycloaddition. This efficient method produces an overall yield of 21% and exhibits high stereoselectivity in producing the required stereocenters. Lewis acid promotes (4 + 2) cycloaddition, yielding a nitronate which undergoes (3 + 2) cycloaddition and produces a nitroso acetal with the necessary stereocenters for (-)-hastanecine.

Enoxysilacyclobutanes obtained from esters undergo uncatalyzed, syn-selective aldol addition reactions with different aldehydes at room temperature. Labeling experiments reveal the occurrence of direct intramolecular silicon group transfer in thermal aldol reactions. Modeling of transition states reveals the preference for a boat transition structure, indicating the source of diastereoselectivity. Analysis of these Michael addition reactions shows a preference for 1,2-addition over 1, 4-addition.

Analysis of the rotational coordinates around the P-C bond in four distinct phosphorus(V)-substituted methyl anions revealed a pair of local minima in the case of constraint-free amino substituents on phosphorus. Effects on the rotation coordinate were more substantial when the amino groups were restricted to local geometries resembling those observed in diazaphosphorinanes.

The pathway for the synthesis of 3,3-and 3,4-substituted pyrrolidines from nitroalkenes and vinyl ethers involves 2 steps. Cyclic nitronates are obtained in anomeric mixtures by Lewis acid-promoted (4 + 2)-cycloadditions, subjected to 2, 2-disubstituted 1-nitroalkenes accompanied by n-butyl vinyl ether. The products of this step, namely nitronates, are reduced by hydrogen in the presence of Adam's catalyst yielding 3,3-disubstituted pyrrolidines in large amounts equivalent to their N-p-toluenesulfonamides.

The synthesis of functionalized 2,2-disubstituted 1-nitroalkenes is successfully carried out by conjugate 1,4-addition of complex zinc cuprates (RCu(CN)Znl) to (E)-1-1nitroalkenes, succeeded by capture with phenylselenenyl bromide. The consecutive oxidative removal yields the respective 2, 2-disubstituted 1-nitroalkenes in relevant amounts. The E/Z isomeric mixtures of 2-alkyl, 2-aryl and alpha-branched 2-alkyl, 2,2-disubstituted nitroalkenes are also synthesized through this pathway. These nitroalkenes serve as substrates for 4 + 2 cycloaddition.

The solution structure and geometry of several Lewis acid-aldehyde complexes were examined using variable-temperature H nuclear magnetic resonance spectroscopy. The results showed that the presence of strong substituent steric effects in the SnCl4 complexation with aldehydes resulted in the formation of an (E)-complex. Additionally, the electronegativity of the sp carbon atom caused the apparent difference in basicity observed between (E)-2-heptanal and 2-heptynal.

The tandem (4 + 2)/(3 + 2) cycloaddition of methyl (E,E)-7-nitro-2,6-dienoate with chiral enol ethers is stereochemically sensitive to the Lewis acid used. The stereoselectivity arises from the endo/exo response of the internal dienophile, whereas the enol ether is restricted to the same diastereomeric face relative to the nitroolefin. It is thus possible to obtain high optical yields of either enantiomer by simply choosing the proper Lewis acid. This is particularly true for structures like the camphor-based vinyl ether.

The tandem (4 + 2)/(3 + 2) cycloaddition of methyl (E,E)-7-nitro-2,6-dienoate with ethyl (E)- and (Z)-1-propenyl ethers involves the creation of three stereogenic centers at each of the cycloaddition stage. Hydrogenolysis of the cycloadducts yields alpha-hydroxy lactams with beta-configuration for the new methyl group. The study points to the influence of the exclusive endo preference of the alkoxy group during the (4 + 2) stage, which forces the alkyl beta-group to take up positions dictated by the dienophile geometry.

The stoichiometry of organocerium additions to hydrazones is studied. With achiral N,N-dimethylhydrazone, a 3:1 methyllithium/cerium(III) chloride mix gives >65% yield. For (S)-(-)-amino-2-(((methoxy)ethoxy)methyl)pyrrolidine hydrazone, on the other hand, the optimum yield is obtained with a 1:1 reagent, although two-thirds of CeCl3 is not used, the methyl nucleophile stoichiometry being two equivalents. The results suggest inhibitory binding of the chelating sidechain to the reagent and the need for reagent coordination to one of the nitrogen lone pairs to activate the hydrazone.

The reaction of nitroalkenes with cyclic alkenes proceeded through Lewis acid mediated cycloadditions forming anti selective nitronates with retention of olefin conformation. Nitrostyrenes underwent intermolecular cyclizations with alkenes and dienes yielding anti-fused and syn-fused cycloadducts, respectively. In addition, structural analyses revealed that the outcome of intramolecular cycloadditions was affected by atom hybridization in the bridging tether.

NMR and X-ray crystallographic methods are used to examine (chloromethyl)zinc and (iodomethyl)zinc cycloprpanation reagents. The study illustrates the formation of the bis(halomethyl)zinc species by the addition of either CH2I2 or ClCH2I to Et2Zn. Chelation to ethers or to acetone stabilizes these highly reactive reagents. The significant rate acceleration of cyclopropanation for oxygen with proximal oxygen substituents is caused by the complex-induced proximity effect, instead of the activation of the reagent. An X-ray crystallographic analysis of an (iodomethyl)zinc complex is also reported.

An efficient enantioselective total synthesis of papulacandin D by a convergent synthetic strategy is described. The reaction involves a silicon-based cross-coupling reaction to construct the key spirocyclic C-aryl glycopyranoside and an enatioselective allylation reaction using a chiral bisphosphoramide for the construction of the C7 stereocenter.