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The reaction of tridentate amidine 2-[Ph2P(O)]C6H4NHC(But)=N(2,6-Me2C6H3) (1) containing the side-chain donor group Ph2P=O with NdCl[N(SiMe3)2]2 (2) in a molar ratio of2:1 afforded the neodymium bis(amidinate) monochloride complex {2-[Ph2P(O)]-C6H4NC(But)N(2,6-Me2C6H3)}2NdCl (3). The neodymium bis(amidinate) monoallyl complex {2-[Ph2P(O)]C6H4NC(But)N(2,6-Me2C6H3)}2Nd(C3H5) (5) was synthesized by the elimination reaction between the tris-allyl derivative Nd(C3H5)3-(C4H8O2)2 (4) and amidine 1 in a molar ratio of 1:2 and by the exchange reaction between equimolar amounts of complex 3 and allylmagnesium bromide (C3H5MgBr). Complex 5 exhibits high activity as an initiator for the ring-opening polymerization of rac-lactide and e-caprolactone, providing the conversion of up to 500 equivalents of the rac-lactide and e-caprolactone within 5 and 2 min, respectively. The resulting polylactide samples have high number-average molecular weights ((47.38–93.02) · 103) and low polydispersity indices (Mw/Mn = 1.18–1.47). The polycaprolactone samples are characterized by high number-average molecular weights ((114.34–237.46) · 103) and a somewhat broadened molecular weight distribution (Mw/Mn = 1.87–2.40).

U okviru ovog rada istražena je adicija Grignardovih reagensa na lakton izveden iz D-riboze s ciljem dobivanja kiralnih tercijarnih alkohola. Iako je uvriježeno kako dva ekvivalenta Grignardova reagensa u reakciji s esterom daju tercijarni alkohol s dva ista supstituenta, u okviru ovog rada ispitana je mogućnost uzastopnog dodavanja dva različita Grignardova reagensa unutar iste reakcije. S tim ciljem provedena je sinteza 5-deoksi-2,3-izopropiliden-D-ribonolaktona kroz nekoliko koraka, te je navedeni spoj korišten kao supstrat za generiranje kiralnih tercijarnih alkohola. Također provedena je i sinteza dva funkcionalizirana alkil-bromida za pripravu Grignardovih reagensa, dok su drugi bili komercijalno dostupni. Dobiveni ribonolakton preveden je u različite kiralne alkohole. U prvom stupnju reakcije adiran je alilmagnezijev bromid, dok je u drugom stupnju dodan drugi Grignardov reagens. Na taj način generirana su 4 kiralna tercijarna alkohola. Produkti su izolirani i okarakterizirani spektroskopskim metodama. Dobiveni rezultati poslužiti će za daljnji razvoj navedene metodologije uvođenja kiralnih tercijarnih alkohola u zahtjevnije molekule što će potencijalno omogućiti efikasniju i jednostavniju pripravu novih djelatnih tvari. In this thesis the addition of Grignard reagent on lactones derived from D-ribose was examined with the intention of generating new chiral tertiary alcohols. Although it is known that the addition of two equivalents of a Grignard reagent to an ester will form a tertiary alcohol with two identical substituents, in this thesis the possibility of a sequential addition of two different Grignard reagents in the same reaction was researched. To that end, 5-deoxy-2,3-isopropylidene-D-ribonolactone was synthesized in four steps and used as a substrate for generating chiral tertiary alcohols. Furthermore, synthesis of two functionalized alkyl-bromide derivatives was performed for the preparation of Grignard reagents with others being commercially available. The synthesized ribonolactone was converted into different chiral tertiary alcohols. In the first step of the reaction, allylmagnesium bromide was added and then in the second step the other Grignard reagent was added. With this approach, four chiral tertiary alcohols were generated. The products were isolated and characterized with spectroscopic methods. The obtained results will be of great use in the further development of this methodology with the purpose of introduction of a new chiral tertiary alcohol group to complex molecules. With this in mind, it is a possibility that this method will provide a more efficient and simpler procedure in the synthesis of new active pharmaceutical ingredients.

The regiospecific characteristics of n-3 polyunsaturated fatty acids (PUFAs) in triacylglycerol (TAG) significantly affect the physicochemical and physiological properties of marine fish oils. In this study, the TAG molecular species composition and positional distributions of fatty acids were investigated in three marine fish species rich in omega-3 PUFAs (anchovy, tuna, and salmon). The regiospecific distribution of the fatty acids was measured with the allylmagnesium bromide (AMB) degradation method. The TAG compositions were analyzed with HPLC and the TAG molecular species were identified with APCI/MS. DHA was preferentially distributed at the sn-2 position of TAG, whereas EPA was evenly distributed along the glycerol backbone. The combinations of FAs, DDO, EOP, EPS, DSS, OOS, and PPS were the predominant TAG molecular species, and OOP, DOS, and DPoPo were the characteristic TAG molecules in the anchovy, salmon, and tuna, respectively. These data can be used to distinguish other marine fish species. The TAG composition categorized by TCN and ECN showed well-structured distributions, with double or triple peaks. These findings should greatly extend the use of marine fish oils in food production and may significantly affect the future development of the fish oil industry.

An efficient triflic acid catalyzed regioselective alkylation of 5-R-1H-tetrazoles with readily available allylcarboranes is reported. The suggested synthetic procedure allows the formation of a variety of carboranyl-substituted tetrazoles in a good yield under mild conditions. Transformations of newly synthesized carboranyl tetrazoles under UV irradiation were studied. Allylcarboranes as starting materials were prepared via Pd-catalyzed cross-coupling reaction of iodocarboranes with allylmagnesium bromide.

Functionalized hydroindole (1), a common chiral synthon, for versatile transformations to synthesize a broad range of Amaryllidaceae alkaloids (AAs) including (−)-crinine, (−)-crinane, (−)-amabiline, (+)-mesembrine, (−)-maritidine, (−)-oxomaritidine, and (+)-mesembrane is reported. Scaffold 1 is found as a prime structural motif in a wide variety of the AAs and is a novel synthon toward designing a divergent route for the synthesis of these natural products. This is established in a few steps, starting from a chiral aza-bicyclo-heptene sulfone scaffold (2) via conjugate addition and concomitant stereoselective ring opening with allylmagnesium bromide, a key step that generates a crucial quaternary stereocenter, fixing the stereochemistry of the rest of the molecule at an early stage. One carbon truncation followed by intramolecular reductive amination led to the desired core 1 in a multigram scale.

A straightforward approach toward enantioenriched α-substituted α,β-unsaturated δ-lactams is described. Although a considerable number of approaches toward α,β-unsaturated δ-lactams have been reported, there are relatively few examples of enantioenriched α,δ-disubstituted α,β-unsaturated δ-lactams formation. The δ-stereocenter was formed by addition of allylmagnesium bromide to an N-tert-butylsulfinyl imine. The α,β-unsaturated δ-lactam was furnished by ring-closing metathesis. Although Baylis–Hillman chemistry failed on this cyclic compound, introduction of the hydroxyethyl group prior to ring-closing metathesis was successful. A Baylis–Hillman reaction was used to introduce the substituent at the α-position of the α,β-unsaturated lactam.

The chelation-control model explains the high diastereoselectivity obtained in additions of organometallic nucleophiles to α-alkoxy ketones but fails for reactions of allylmagnesium halides. Low diastereoselectivity in ethereal solvents results from no chelation-induced rate acceleration. Additions of allylmagnesium bromide to carbonyl compounds are diastereoselective using CH2Cl2 as the solvent even though rate acceleration is still absent. Stereoselectivity likely arises from the predominance of the chelated form in solution. Therefore, a revised chelation-control model is proposed.

The development of a synthesis of the C1–C16 fragment of bryostatins in which the key step is a stereoselective oxy-Michael reaction used to assemble the cis-2,6-disubstituted tetrahydropyran with the exocyclic alkene already installed, is described. Following early work using Stille reactions to prepare precursors for oxy-Michael reactions, a more efficient route was devised based on a ketophosphonate-aldehyde condensation to prepare the key dienone. Synthesis of the aldehyde required for the ketophosphonate condensation involved the highly stereoselective addition of a diorganocuprate derived from allylmagnesium bromide and copper(I) iodide to the methyl 5-hydroxyhex-2-ynoate prepared by ring-opening of a protected glycidol using lithiated methyl propiolate. Ester reduction, selective alcohol protection and oxidative cleavage of the terminal double bond gave the required aldehyde. The ketophosphonate was prepared in 13 steps from (R)-pantolactone using a synthesis based on a chelation controlled aldol condensation and an anti-selective reduction of a 3-hydroxyketone. Following the ketophosphonate-aldehyde reaction, selective deprotection followed by treatment with base effected the oxy-Michael reaction that gave the cis-2,6-disubstituted tetrahydropyran via thermodynamic control. Subsequent functional group manipulation led to the synthesis of a hydroxy ester that corresponded to the C1–C16 fragment of the bryostatins in 23 steps from (R)-pantolactone. The synthesis was repeated using slightly different protecting groups for a study of a ring-closing metathesis approach to the bryostatins.

A straightforward approach toward enantioenriched α-substituted α,β-unsaturated δ-lactams is described. Although a considerable number of approaches toward α,β-unsaturated δ-lactams have been reported, there are relatively few examples of enantioenriched α,δ-disubstituted α,β-unsaturated δ-lactams formation. The δ-stereocenter was formed by addition of allylmagnesium bromide to an N-tert-butylsulfinyl imine. The α,β-unsaturated δ-lactam was furnished by ring-closing metathesis. Although Baylis–Hillman chemistry failed on this cyclic compound, introduction of the hydroxyethyl group prior to ring-closing metathesis was successful. A Baylis–Hillman reaction was used to introduce the substituent at the α-position of the α,β-unsaturated lactam.

The synthesis of polyhydroxylated 2-allylpyrrolidines from sugar-derived bromonitriles in a cascade addition of allylmagnesium bromide/SN2 cyclization/reduction with Zn(BH4)2 is described. The stereochemical course of the reduction step is rationalized. Two of the obtained compounds are transformed into stereoisomers of naturally-occurring iminosugar (+)-lentiginosine. In an alternative approach, 2,2-diallylpyrrolidines are obtained from bromonitriles in a cascade addition of allylmagnesium bromide/SN2 cyclization/addition of another equivalent of allylmagnesium bromide.

An allyl group was introduced to SBA-15 by the reaction of allylmagnesium bromide with chlorinated SBA-15 obtained by the treatment of calcined SBA-15 with thionyl chloride. The allyl group was con...

A copper-catalyzed conjugate addition of Grignard reagents to 1-(N,N-diisopropylcarbamoyloxy)-1-tosyl-1-alkenes led to 1-(N,N-diisopropylcarbamoyloxy)-1-tosyl-2-branched alkanes. Various copper ligands were screened for this reaction. From certain substrates and allylmagnesium bromide, several Josiphos ligands gave low to moderate asymmetric inductions, along with good diastereoselectivity. The stereochemistry of the 1-(N,N-diisopropylcarbamoyloxy)-1-tosyl-2-branched alkanes from this reaction was assigned by comparison with the same products from another synthetic route using chiral pool synthesis and stereoselective lithiation methods.

The three title alkaloids were separately prepared in stereocontrolled fashion from a common tetraoxobispidine precursor, 3,7-diallyl-2,4,6,8-tetraoxo-3,7-diazabicyclo[3.3.1]nonane (16). Bisimide 16 was generated from malonate via acid promoted cyclization of the Knoevenagel condensation adduct 1,1,3,3-propanetetracarboxamide. (+/-)-alpha-Isosparteine (dl-2) was elaborated from 16 in 28% overall yield by a two-directional synthetic sequence composed of four reactions: double addition of allylmagnesium bromide, ring-closing olefin metathesis (RCM), hydrogenation, and borane mediated reduction. (+/-)-beta-Isosparteine (dl-3) was targeted along similar lines by a strategic reversal in allylation and reduction operations on the core synthon. Thus, 16 was advanced to dl-3 in five steps and 12% overall yield by a reaction sequence commencing with sodium borohydride mediated reduction and followed by double Sakurai-type allylation of the resulting bishemiaminal. The synthesis of dl-3 was concluded by RCM and then global reduction (H2, Pd/C; LiAlH4). The final target, (+/-)-sparteine (dl-1), was secured in six steps and 11% overall yield from 16 by monoreduction and Sakurai allylation, followed by allyl Grignard addition and then RCM and global reduction as before. Reasons for the inherent C2-type regioselectivity of net double nucleophilic additions to tetraoxobispidines are discussed and enantioselective oxazaborolidine mediated reduction of the N,N'-dibenzyl congener of 16 is reported.

The synthesis of polyhydroxylated 2-allylpyrrolidines from sugar-derived bromonitriles in a cascade addition of allylmagnesium bromide/SN2 cyclization/reduction with Zn(BH4)2 is described. The stereochemical course of the reduction step is rationalized. Two of the obtained compounds are transformed into stereoisomers of naturally-occurring iminosugar (+)-lentiginosine. In an alternative approach, 2,2-diallylpyrrolidines are obtained from bromonitriles in a cascade addition of allylmagnesium bromide/SN2 cyclization/addition of another equivalent of allylmagnesium bromide.

Starting with Δ15-17-ketosteroids, applying Normant reaction with allylmagnesium bromide and anionic Cope rearrangement of the formed allyl alcohol, 15α-derivatives of androstane series were prepared. The latter were brought into Wittig reaction with an ylide generated from ethyltriphenylphosphonium bromide, and the product was subjected to ene reaction to provide 15α-substituted pregnanes.

A novel one-pot synthesis of α,α-disubstituted secondary arylamines from oxime ethers has been developed by two separate additions of organometallic reagents. As a related arylamine construction, very efficient synthesis of N-(diallyl)methyl arylamines is achieved via domino reactions involving addition-eliminative re-arrangement-addition reactions of acyclic and cyclic oxime ethers with allylmagnesium bromide.

The vicinal functionalization of N-alkoxyenamines, derived in situ from aldehydes and isoxazolidines, has been achieved with the formation of two new carbon–carbon bonds by utilizing an organo-aluminum reagent and subsequent allylmagnesium bromide or tributyltin cyanide as external carbon-centered nucleophiles. By changing the second carbon nucleophile, various amine derivatives were obtained in good yields.

Symmetrical spiro-1,3-bisketone (IV) is synthesized by ring-closure metathesis reaction of tetraene (I) obtained by Grignard reaction of a dialkenyl compound and allylmagnesium bromide.

The one-pot sequential reaction of a chromium alkoxycarbene complex, a ketone or ester lithium enolate, and allylmagnesium bromide enabled the selective synthesis of novel diastereomerically pure pentasubstituted cyclopentanols or tetrasubstituted 1,4-cyclohexanediols, depending on the degree of substitution at the Cbeta position of the enolate anion. A few exceptions have been encountered in which tetrasubstituted cyclopentanols or pentasubstituted 1,4-cyclohexanediols were selectively formed. The use of 2-iodoethoxycarbene complexes gave access to 1,2,4-cyclohexanetriols. These multicomponent-coupling reactions involved the formation of lithium alkylpentacarbonylchromates as key intermediates, which further evolved through intramolecular processes, such as insertion of an alkene, CO insertion or addition to a carbonyl group, and, moreover, could be trapped in intermolecular reactions with different electrophiles and styrene. The substitution pattern of the alkylchromate carbon chain has been proposed to control the nature of the annulation process.

N,N-Bis(3-butenyl)amines can be prepared by the double allylation of either (2-azaallyl)stannanes or (2-azaallyl)nitriles, both of which thereby act as synthetic equivalents to amine alpha,alpha'-dications (2-azaallyl dications). Allylmagnesium bromide is the reagent of choice for the double allylation of both substrates, although allyllithium also effects the double allylation of (2-azaallyl)nitriles. Ring-closing metathesis can be performed on the N-protected amines, or with in situ protonation, on the free amines to provide 2,3,6,7-tetrahydroazepines. (2-Azaallyl)nitriles can also be monoallylated to provide N-(3-butenyl)aminonitriles, whereas the double allylation of (2-azaallyl)stannanes cannot be stopped at monoallylation. (2-Azaallyl)silanes undergo monoallylation to give N-(3-butenyl)aminosilanes but do not undergo double allylation.

The asymmetric allylboration of N-H aldimines, generated from either N-trimethylsilyl or N-diisobutylalanyl precursors, with B-allyl-9-borabicyclo[3.3.2]decane is described. The desired homoallylic amines are obtained efficiently (60-90 %) and selectively (60-89 % ee). A non-oxidative work-up procedure has also been developed for this new method, which permits the recovery of the air-stable pseudoephedrine (PE) complex (50-70 %), which is conveniently converted back to B-allyl-9-borabicyclo[3.3.2]decane (98 %) with allylmagnesium bromide in ether for its reuse in the asymmetric allylboration process. Additional studies were conducted to better understand these processes and the origin of the observed enantioselectivity.

The convergent syntheses of three generations of carbosilane dendrimeric carbodiimides are described. The wed e-type building blocks were synthesized in a divergent way, starting from allyl chloride and a repetitive sequence of hydrosilylation with HSiCl3 and a Grignard reaction with allylmagnesium bromide. Hydrogenation of the terminal double bonds led to inert and stable wedges. The chloride substitutent at the focal point was transformed into several functional groups that eventually led to dendrimeric structures with a carbodiimide core. The extent of the site isolation effect of the dendrimers was studied with dilution experiments monitored by FT-IR spectroscopy on the corresponding dendrimeric ureas. These studies showed that only the first generation self-aggregates via hydrogen bonding, while the second and the third do not, implying isolation of core-bound moieties. The dendrimeric carbodiimides mediated lactamization reactions to obtain homodiketopiperazines.

Diferrocenyl(methylthio)cyclopropenylium iodide reacts with organometallic compounds (methyllithium, benzyl- and ethylmagnesium chlorides, and allylmagnesium bromide) to yield 2,3-diferrocenyl-1-methylthio-1,3-dienes or -1,3,5-triene together with 3,3-dialkyl-1,2-diferrocenylcyclopropenes. We present data from X-ray diffraction analyses of (E)-2,3-diferrocenyl-1-methylthio- and (E,Z)-2,3-diferrocenyl-1-methylthio-4-phenyl-1,3-butadienes. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

The remarkable versatility and selectivity of the 10-(trimethylsilyl)-9-borabicyclo[3.3.2]decanes (10-TMS-9-BBDs) in the allyl- and crotylboration of representative aldehydes are reported. The new reagents are prepared through air-stable crystalline pseudoephedrine borinic ester complexes of the 10-TMS-9-BBDs (4), which are available in 63% overall yield from B-MeO-9-BBN through a simple two-step procedure. These complexes 4 are directly converted to the corresponding B-allyl-10-TMS-9-BBDs (1) with allylmagnesium bromide, which either can be isolated (98%) or used in situ for the allylations. The remarkable enantioselectivity (96 toor =99% ee) of these reagents in the rapid (3 h), asymmetric allylboration process at -78 degrees C is only slightly diminished when it is conducted at 25 degrees C, a phenomenon attributable to its rigid bicyclic structure. In addition to providing the homoallylic alcohols 6 efficiently (68-80%), the procedure also permits the efficient recovery of 4 (68-84%) for the direct regeneration of 1. Alternatively, an oxidative workup procedure can be used for the preparation of 6. The reagent gives predictable stereochemistry and exhibits an extremely high level of reagent control in the allylboration of d-glyceraldehyde acetonide. A simple and efficient procedure has been developed for the preparation of all four geometric and enantiomeric isomers of the B-crotyl-10-TMS-9-BBDs (10) from optically pure enantiomers of B-MeO-10-TMS-9-BBD (3). These reagents 10 also add rapidly (3 h) and efficiently to representative aldehydes at -78 degrees C, providing ready access to all four of the possible stereoisomers of the beta-methyl homoallylic alcohols 12-15 (69-92%) in high dr (or =98:2) and ee (94-99%).

Efficient Pauson-Khand reactions on quinolines bearing 1-en-7-ynes features gave tetrahydrocyclopenta[c]acridine derivatives. The quinoline intermediates were obtained in two steps: a Sonogashira reaction with functionalized alkynes (TMS, Bu, Ph, CHB 2 OTHP) followed by a Grignard reaction with allylmagnesium bromide. The sequence provides new acridine structures in four high yielding steps from commercially available quinolines.

Cytotoxic pyrido[1,2- e ]purines are readily available from 8,9-diallylpurines by ring-closing metathesis (RCM) followed by oxidation. The 8,9-diallylpurines were synthesized conveniently by addition of allylmagnesium bromide to the corresponding C-8 unsubstituted purines, followed by rearomatization of the adducts.

A synthesis of the C(1)–C(16) fragment of the brysostatins has been developed. Key steps are the stereoselective copper(I) catalysed addition of allylmagnesium bromide to an alkynyl ester, a condensation of a βγ-unsaturated aldehyde with a ketophosphonate, and the formation of the B-ring under mild conditions by stereoselective intramolecular conjugate addition.

New N-aryl substituted 2-(α-naphthyl)-4-thiazolidinones were prepared by the cyclocondensation of α-mercaptoacetic acid and corresponding N-(α-naphthyliden)anilines. The same starting materials were utilized to obtain a new series of N-aryl-N-[1-(α-naphthyl)but-3-enyl]amines, which was synthesized through an addition of the Grignard reagent (allylmagnesium bromide) to the double bond CN of the aldimines. The antichagasic and trichomonacidal in vitro activity, as well as, the antifungal and cytotoxic properties of some of these compounds were evaluated.

The synthesis of (1R,2R,3S,9aR) and (1R,2R,3S,9aS) trihydroxy quinolizidine alkaloids 3a and 3b from D-glucose derived nitrone 4 is described. The key transformation involves the 1,3-addition of allylmagnesium bromide to nitrone 4 that afforded high diastereoselectivity in the presence of TMSOTf. The N-O bond reductive cleavage, N-Cbz protection, ozonolysis, Wittig olefination, lactum formation and reductive amination cascade afforded the target compounds 3a and 3b in good overall yield.

The use of the Barbier‐Grignard reaction, where premixed allyl bromide and the carbonyl compound are added to magnesium in ether, is reported for the synthesis of homoallylic alcohols. This reaction provides good to excellent yields of most homoallylic alcohols with minimal formation of Wurtz coupling products.

A new route is presented to prepare analogs of nucleosides homologated at the 3′- and 5′-positions. This route, applicable to both the D- and L-enantiomeric forms, is suitable for the preparation of monomeric bis-homonucleosides needed for the synthesis of oligonucleotide analogs. It begins with the known monobenzyl ether 3 of pent-2-yne-1,5-diol, which is reduced to alkenol 4. Sharpless asymmetric epoxidation of 4, followed by opening of the epoxide 5 with allylmagnesium bromide, gives a mixture of diols 6 and 7. Protection of the primary alcohol as a silyl ether followed by treatment with OsO4, NaIO4, and mild acid in MeOH, followed by reduction, yields (2R,3R) {{[(tert-butyl)diphenylsilyl]oxy}methyl}tetrahydro-2-(2-hydroxyethyl)-5-methoxyfuran (=methyl 3-{{[(tert-butyl)diphenylsilyl]oxy}methyl}-2,3,5-trideoxy-α/β-D-erythro-hexafuranoside; 10) (Scheme 1). Protected nucleobases are added to this skeleton with the aid of trimethylsilyl triflate (Scheme 2). The o-toluoyl (2-MeC6H4CO) and p-anisoyl (4-MeOC6H4CO) groups were used to protect the exocyclic amino group of cytosine. The bis-homonucleoside analogs 11 and 14a are then converted to monothiol derivatives suitable for coupling (Schemes 3 and 4) to oligonucleotide analogs with bridging S-atoms. This synthesis replaces a much longer synthesis for analogous nucleoside analogs that begins with diacetoneglucose (=1,2 : 5,6-di-O-isopropylideneglucose), with the stereogenic centers in the final products derived from the Sharpless asymmetric epoxidation. The new route is useful for large-scale synthesis of these building blocks for the synthesis of oligonucleotide analogs.

2,3;5,6-Di-O-isopropylidene-α-d-mannofuranosyl chloride reacted with allylmagnesium bromide with preferential inversion of the anomeric configuration to furnish a mixture of the 1-allyl-1-deoxy-β- and α-d-mannofuranoses. Separation of β and α derivatives was possible only after conversion to the 1-allyl-1-deoxylyxofuranoses 2 and 3. The β configuration of the predominant product 2 was proved using the NOE method.

Treatment of chloro(phenyl)germanes with allylmagnesium bromide yielded allyl(phenyl)germanes. Coupling of the allyl(phenyl)germanes with aryl halides in 1,4-dioxane in the presence of aqueous NaOH...

The synthetic utility of N-alkoxyimidoyl halides is demonstrated using the palladium-catalyzed cross-coupling reaction. The Sonogashira and Suzuki-Miyaura coupling reactions of N-alkoxyimidoyl bromides produced versatile ketoxime ethers in good to excellent yields. A one-pot reaction of the imidoyl bromides with arylboronic acid and allylmagnesium bromide to produce N-arylamines via Suzuki-Miyaura coupling followed by domino reaction involving sequential addition-eliminative rearrangement-addition reactions was developed.

trans-Metanicotine, a subtype (alpha4beta2)-selective ligand for neuronal nicotinic acetylcholine receptor, is under clinical phase for Alzheimer's disease. An efficient synthetic route for (+/-)-methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-amines, derivatives of trans-metanicotine, was explored. Allylation reaction of aryl aldimines with allylmagnesium bromide in THF gave (+/-)-methyl-(1-aryl-but-3-enyl)-amines. Protection of the amines with the Boc group and following Heck reaction of the N-Boc amines with 3-bromopyridine gave (+/-)-methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-carbamic acid tert-butyl esters. Deprotection of the N-Boc group in aqueous 1N-HCI solution gave the titled amines in good yields. Thus, trans-metanicotine analogues modified at the a-position of the methylamino group with aryl groups were obtained in 5 steps.

The reaction of open-chain or cyclic alpha-diketones with specific omega-alkenyl organometallics leads readily under the proper conditions to 1,2-diols bonded to terminal olefinic chains. With 1-phenyl-1,2-propanedione, biacetyl, and cyclohexane-1,2-dione, allylindation in aqueous THF proceeds readily at both adjacent carbonyls. For cyclododecane-1,2-dione, recourse must be made to allylmagnesium bromide for completing the second-stage condensation. Grignard reagents have also served well as reactants for biacetyl monoadducts. In contrast, monoallylated camphorquinone is reluctant to couple to Grignard reagents and reacts only when Barbier-type alkyllithium reactions are applied. The ring closing metatheses of these products have been examined. Where six-membered ring formation operates, cyclization can be performed directly on diols. When larger rings are involved, the diols will react only if structural preorganization capable of facilitating mutual approach of the two double bonds is at play. For this purpose, the prior conversion to a cyclic carbonate holds considerable utility. In the latter setting, saponification must precede the diol cleavage step which has been performed with lead tetraacetate. The latter reagent also exhibits the very beneficial effect of facilitating removal of ruthenium and phosphorus byproducts generated during the metathesis step. This chemistry conveniently lends itself to the controlled intercalation of multiple methylene groups between the carbonyl carbons of readily available alpha-diketones to deliver linear or cyclic products.

[reaction in text] Treatment of (2-azaallyl)stannanes (i) with 2.2 equiv of allylmagnesium bromide afforded good yields of N,N-bis(3-butenyl)amines derivatives (ii), which were subjected to ring-closing metathesis to afford 2,3,6,7-tetrahydroazepines (iii). Thus, (2-azaallyl)stannanes are the synthetic equivalents of amine alpha,alpha'-dications.

Intramolecular photocycloaddition of 2-pyridones connected through a four-carbon tether (6-[4-(1,2-dihydro-1-methyl-2-oxo-3-pyridinyl)-4-[[(1,1-dimethylethyl)++ +dimethylsilyl]oxy]butyl]-4-methoxy-1,3-dimethyl-2(1H)-pyridinone) yields a single tetracyclic product with four new stereogenic centers. The diastereoselectivity of this [4 + 4] reaction is fully controlled by a stereogenic carbon of the tether. Treatment of the photoproduct with osmium tetraoxide transforms the alkene to a diol and the enol ether to an alpha-hydroxy ketone, with stereocontrol dictated by nearby lactams that block one face of each alkene. Allylmagnesium bromide addition to the ketone also yields a single diastereomer, but unexpectedly this product results from approach of the nucleophile to the most-hindered face of the ketone. Study of this reaction in a model system has found the allylic nucleophile to be unique, with nonallylic reagents approaching along the expected, least-hindered path. This contrasteric addition likely results from coordination of the allylic nucleophile to the nearby amide. The amide can therefore act either as a steric shield or as a directing group. The three steps of photocycloaddition, cis-hydroxylation, and nucleophilic addition constructs both quaternary carbons of the cyclooctane and four of the five stereogenic centers found in the eight-membered ring of Taxol.

A method for synthesizing growth ring-type dendritic macromolecules starting from siloxane polymer with SiH bonds [Me3SiO(MeSiOH)nSiMe3] as the core and dichlorovinylsilane, dichloromethylsilane, lithium phenylacethylide, and allylmagnesium bromide as the building blocks is described. The siloxane polymer was produced to the second dendritic generation by the repetition of hydrosilation and alkenylation as well as by an alkynylation process. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 724–729, 2000

Competition kinetics are useful for estimation of the reactivities of Grignard reagents if the reaction rates do not differ widely and if exact rates are not needed. If the rate of mixing is slower than the rate of reaction, the ratios between the rates of fast and slow reagents are found to be too small. This is concluded from experiments in which results obtained by competition kinetics are compared with results obtained directly by flow stream procedures. A clearer picture of the reactivity ratios is obtained when the highly reactive reagent is highly diluted with its competitor. A fast reagent may account for almost all the product even when present as only 1 part in 100 parts of the competing agent. In this way allylmagnesium bromide is estimated to react with acetone, benzophenone, benzaldehyde, and diethylacetaldehyde ca. 1.5 x 10(5) times faster than does butylmagnesium bromide. The rates found for the four substrates do not differ significantly, and it seems possible that there is a ceiling over the rate of reaction of this reagent, for example, caused by diffusion control. This may explain that competition kinetics using allylmagnesium bromide have failed to show kinetic isotope effects or effects of polar substituents with isotopically or otherwise substituted benzophenones. A recently reported alpha-deuterium secondary kinetic isotope effect for the reaction of benzaldehyde with allylmagnesium bromide was observed at -78 degrees C, but was absent at room temperature. It is suggested that the reaction of benzophenone and benzaldehyde with allylmagnesium bromide has a radical-concerted mechanism since no radical-type products are produced and since no color from an intermediate ketyl is observed even at -78 degrees C.

The stereochemical course of the hydride reduction and of the 1,2-addition of allylmagnesium bromide as well as the Normant reagent to 1 has been determined.

Addition of organolithium or Grignard reagents to (R)- or (S)-O-(1-phenylbutyl)aldehyde oximes 1 in the presence of boron trifluoride–diethyl ether results in the formation of hydroxylamines 2 in good to excellent diastereoselectivity. Subsequent cleavage of the N–O bond with zinc–acetic acid–ultrasound, and carbamate formation, gives N-protected amines 3 in good enantiomeric purity (77–100% ee). When allylmagnesium bromide was used as the organometallic reagent, the resulting hydroxylamines were converted into β-amino acid derivatives 4 and γ-amino alcohols 5.

A concise total synthesis of enantiopure (+)-preussin (1) from L-phenylalanine (3) is described. The key steps involve i) syn-selective formation of the 1, 2-amino alcohol fragment2, via chelation controlled addition of allylmagnesium bromide toN-Boc-phenylalaninal, and ii) L-selectride® mediated stereoselective reduction of the ketone8 to the alcohol derivative9 with the required stereochemistry for final cyclization. A concise total synthesis of natural (+) preussin has been developed starting from readily available L-phenylalanine. Download : Download full-size image

Compound CpMo( η 3 -C 3 H 5 ) 2 , 3, has been synthesized from CpMoCl 4 and four equivalents of allylmagnesium bromide. While the compound is stable in donor solvents at room temperature, warming in refluxing MeCN induces the formation of 1,5-hexadiene by a metal-mediated allyl-allyl coupling process. Treatment of 3 with Bu t NC at room temperature affords CpMo( η 3 -C 3 H 5 )(Bu t NC) 2 , 4. A similar reduction with presumed allyl radical loss occurs for [CpMo( η 3 -C 3 H 5 )( η 4 -C 4 H 6 )] + , [1c] + , to afford [CpMo( η 4 -C 4 H 6 )(Bu t NC) 2 ] + , 5. Treatment of [1c] + with methyllithium affords two products, the major one (1c) corresponding to the one-electron reduction pathway and the minor one (CpMo( η 3 -C 3 H 5 )( η 3 -C 3 H 4 -1-Et), 6, ca. 4%) corresponding to nucleophilic addition. Protonation of the 1c:6 mixture affords a 2:1 mixture of cis and trans 2-pentene, in addition to propene. The room temperature Cp 2 Fe + PF 6 − oxidation of 3 in MeCN induces the immediate release of 1,5-hexadiene. The oxidation of 3 in Bu t NC gives complexes [CpMo(CNBu t ) 3 ( η 2 −CH 2 CHCH 2 CH 2 CH=CH 2 )] + PF 6 − (7, major) and [ CpMo ( CNBu t ) 4 ] + PF 6 − (8, minor). Finally, the oxidation of 3 in the presence of butadiene, followed by treatment with CD 3 CN, affords a mixture of [ CpMo ( η 3 : η 3 − C 3 H 4 CH 2 CH 2 C 3 H 4 )(CD 3 CN)] + PF 6 − , 9, and [ CpMo ( η 4 − C 4 H 6 )(CD 3 CN) 2 ] + PF 6 − , 10. Thermal decomposition of this mixture affords butadiene and 1,5-cyclooctadiene.

Regioselective addition of allylmagnesium bromide to β-ketodithioesters (I) produces β-allyl-β-hydroxydithioesters (III).

Starting with 2,4,6,8-tetramethyl-2,4,6,8-tetravinyl-2,4,6,8-tetrasila-1,3,5,7-tetraoxacyclooctane (Me(CH2CH)SiO)4 as a core molecule, a succession of alternate platinum-catalyzed hydrosilations of all vinyl groups with HSiMeCl2, as well as alkenylation with allylmagnesium bromide, provided the third generation (G3) as divergent growth of siloxane-based dendrimers. The reaction path of the repetitive allylation/hydrosilation cycles is controlled with NMR spectroscopic analyses. Each of the two steps provided quantitative yields of pure dendrimers. We also changed the simple construction of the G3P molecule into materials with special functions, such as by adding phenylethynyl and p-bromophenoxy groups on its periphery.

A new chiral (Rs)-2-phenyl-2-propyl sulfinamide has been designed and synthesized; its derived aldimines and ketimines have been applied for asymmetric addition reaction with allylmagnesium bromide. The reaction was conveniently performed at room temperature to give a series of homoallylic amines in high yields (up to quant) and diastereoselectivity (up to >99% de). The pure products were obtained by relying on group-assisted purification (GAP) chemistry to avoid traditional purification methods of column chromatography or recrystallization. The conversion of disulfide to (Rs)-thiosulfinate which contains a newly generated polar group was also confirmed to be of the GAP chemistry in which washing crude product can generate pure enantiomer. The absolute stereochemistry has been determined by X-ray analysis.