Intramolecular [2 + 2]cycloadditions of dialkylketenes with alkenes. Regiochemistry of intramolecular [2+2]cycloadditions of ketenes with alkenes

Unsaturated dialkylketenes 7a, 7b and 7c undergo intramolecular [2 + 2]cycloadditions to give 8a (45%), 9b (23%) and 9c (45%). Intramolecular cycloadditions of dialkylketenes give higher yields than intramolecular cycloadditions of monoalkylketenes, even though dialkylketenes are less reactive than monoalkylketenes. An intramolecular competition experiment with ketene 17 establishes that trans-alkenes are approximately 33 times more reactive than cis-alkenes in intramolecular cycloadditions. Ketene 36 furnishes 22% of the expected bicyclo[3.2.0]heptanone 37 and 28% of bicyclo[3.1.1]heptanone 38.     

Stereocontrolled diels-alder cycloadditions of sugar-derived dihydropyranones with dienes

2-Acetoxy-3,4-di-O-acetyl-D-arabinal (6), similar to its D-xylo analogue 4, reacted with benzyl alcohol by the tin(IV) chloride-promoted glycosylation to produce optically active (S)-2-benzyloxy-2H-pyran-3(6H)-one (8a). The L-arabinal derivative (5) gave 9a, the dihydropyranone enantiomer of 8a. These results indicated that the configuration of the C-4 stereocenter in the starting glycal defines the configuration of the new chiral center in the resulting dihydropyranone. The influence of other catalysts (BF(3) or iodine) employed for the glycosylation on the optical purity of the dihydropyranone was studied. Enantiomerically pure dihydropyranones 8b and 9c were obtained using chiral alcohols ((R)- and (S)-2-octanol, respectively) as glycosylating agents. Compounds 8a,b and 9a,c proved to be reactive dienophiles in thermal and Lewis acid-promoted Diels-Alder reactions. The addition of 2,3-dimethylbutadiene, cyclopentadiene, and 1,3-cyclohexadiene to the beta-pyranones 8a,b led to the corresponding adducts 10a,b, 12a,b, and 16a,b as major products. Enantiomeric cycloadducts were synthesized from the alpha-pyranones 9a,c. The main products were formed by highly facial-diastereoselective addition of dienes to the pyranone ring, guided by the sterical hindrance of the alkoxy substituent of the C-2 stereocenter. As cycloadditions with cycloalkadienes were also highly endo diastereoselective, these reactions gave access to pure tetrahydrobenzopyranones that carry a multitude of stereogenic centers installed in a predictable way.     

Bridged tetraquaternary salts from N,N'-polyfluoroalkyl-4,4'-bipyridine

4,4'-Bipyridine (1) with excess of polyfluoroalkyl bromide or iodides 2a-d at 100-110 degrees C without solvent gave the monoquaternary salts 3a-d in >90% yields. However, 1 with 2.5 equiv of 2a-c in DMF at 110 degrees C resulted in the diquaternary salts 5a-c in >85% yields. In DMF, 5a-c were obtained in comparable yields when a molar excess of 2a-c reacted with 3a-c. 1,4-Dibromobutane with 3a,b in DMF at 100 degrees C led to the tetraquaternary salts 7a,b in approximately 85% yields. In water or acetone/water as a solvent, salts 3a-d and 5a-c were metathesized with LiN(SO(2)CF(3))(2) and KSO(3)CF(3) to produce monoquaternary ionic liquids 4a-h in >88% yields and diquaternary ionic liquids 6a-f in >86% yields, respectively. Tetraquaternary ionic liquids 8a,b were obtained when LiN(SO(2)CF(3))(2) was reacted with salts 7a,b. These compounds were stable to 340 degrees C as determined by DSC. They are the first N-mono-, N,N'-di-, and N,N,N',N'-tetra-4,4'-polyfluoroalkylbipyridinium quaternary salts and ionic liquids.     

Intramolecular Diels-Alder reactions of brominated masked o-benzoquinones. A detour method to synthesize highly functionalized oxatricyclic [m.3.1.0] ring systems from 2-methoxyphenols

Intramolecular Diels-Alder (IMDA) reactions of masked o-benzoquinones (MOBs) 5a-d to 7a-d and 17a-d to 19a-d generated in situ from 2-methoxyphenols 2-4 and 14-16, respectively, in the presence of alkenols 1a-d, resulting in highly functionalized oxatricyclic [m.3.1.0] ring systems are described. The MOBs 5a-d to 7a-d underwent the IMDA reactions to furnish the adducts 8a-d, 10a-d, and 12a-d (direct method) in poor yields with the concomitant formation of considerable amounts of unexpected byproducts 9a-d, 11a-d, and 13a-d, respectively. To avoid the formation of byproducts and to improve the yields of the desired cycloadducts, a detour method comprising sequential bromination of 2-methoxyphenols 2-4, tandem oxidative acetalization-Diels-Alder reaction, and debromination has been developed. The oxidation of bromophenols 14-16 in the presence of alkenols 1a-d produced the corresponding MOBs 17a-d to 19a-d, which underwent cycloaddition to afford the cycloadducts 20a-d to 22a-d, respectively, as sole products in good to high yields in a highly regio- and stereoselective manner. Treatment of the bromoadducts 20a-d to 22a-d with tributylammonium formate-palladium reagent produced the corresponding debrominated products 8a-d, 10a-d, and 12a-d in high to excellent yields. In general, the latter oxatricycles were obtained in higher overall yields via the detour method than those via the direct method.     

Preparation and antimicrobial studies of acyclic sulfamates.

A series of acyclic sulfamates have been prepared and tested for antimicrobial activity. Thus, the oxysulfonyl isocyanates, ROSO2NCO (1a, R = 4-methoxyphenyl; 1b, R = phenyl; 1c, R = 4-chlorophenyl and 1d, R = 2,2,2-trifluoroethyl) have been prepared in 76-91% yield from chlorosulfonyl isocyanate. Treatment of 1a-d with glycidol gave the glycidyl carbamates 2a d. Internal cyclisation afforded the corresponding 4-hydroxymethyl-2-oxazolidinones 3a-d, which in turn were hydrolysed to give the free amino alcohols 4a-d. The yields were in the range 39-85%. A preliminary agar diffusion test of 2a-d, 3a-d, 4a-d indicated 2a-d and 3c to be possible antimicrobial agents. A more thorough analysis of these compounds revealed a minimum inhibition concentration (MIC) of 128 and 64 mg l-1 for glycidyl p-methoxyphenoxysulfonylcarbamate (2a) and glycidyl phenoxysulfonylcarbamate (2b) respectively, against Branhamella catarrhalis.     

First Exclusive Regioselective Fragmentation of Primary Ozonides Controlled by Remote Carbonyl Groups and a New Method for Determining the Regiochemistry of Carbonyl Oxide Formation

The first exclusive regioselective fragmentation of primary ozonides controlled by remote carbonyl groups on ozonolysis of norbornene derivatives and reaction of final ozonides with triethylamine as a new probe for determining the regiochemistry of carbonyl oxide formation from primary ozonide fragmentation are reported. Ozonolysis of the endo adducts 3a-d and the deuterated compounds 8a and 8b in CDCl(3) at -78 degrees C gave the final ozonides 4a-d, 9a, and 9b as the sole products (>95%), respectively. No detectable amount of the isomeric final ozonides 5, 10, 11, and 12 was obtained. A mechanism is proposed to account for the exclusive regioselective fragmentation of the primary ozonides. Ozonolysis of 3a-d, 8a, and 8b in CH(2)Cl(2) at -78 degrees C followed by treatment with triethylamine exclusively gave the convex tetraquinane oxa cage compounds 16a-d, 19a, and 19b in 85-90% yields, respectively. No detectable amount of the other regioisomers 17a-d, 20a, and 20b was obtained. Ozonolysis of 3a-d, 8a, and 8b in CH(2)Cl(2) at -78 degrees C followed by reduction with dimethyl sulfide gave the tetraacetal tetraoxa cage compounds 21a-d, 23a, and 23b in 85% yields, respectively. The difference in function between triethylamine and dimethyl sulfide in reaction with final ozonide is demonstrated. Ozonolysis of the endo adducts 24a and 24b in CDCl(3) at -78 degrees C exclusively gave the final ozonides 27a and 27b, respectively. The order of the preference of various remote carbonyl groups to control the fragmentation of the primary ozonides formed by ozonolysis of norbornene derivatives is investigated. Ozonolysis of the endo esters 32a-c in CH(2)Cl(2) at -78 degrees C followed by reduction with dimethyl sulfide gave the new tetraacetal oxa cages 35a-c, with an alkoxyl group directly on the skeleton, and the novel triacetal oxa cages 36b and 36c, respectively. The structures of triacetal oxa cages are proven for the first time by X-ray analysis of the crystalline compound 36c.     

Preparation of 5-sulfonylpyrimidines from β-keto, β-cyano-, and β-ethoxycarbonyl-β-sulfonylenamines

β-Keto-β-sulfonylenamines 2a,b reacted with benzamidine or guanidines to give 2,4-disubstituted 5-methanesulfonylpyrimidines 3a-d , whose methanesulfonyl groups were substituted by n-butyllithium or alkylmagnesium bromides to yield 2,4-disubstitued 5-alkylpyrimidines 6a-d. 2-Substituted 4-amino-5-sulfonylpyrimidines 7a,b, 8 and 2-substituted 5-benzenesulfonylpyrimidin-4-ones 9a,b were similarly obtained from β-cyano-β-sulfonylenamines 2c,d and β-ethoxycarbonyl-β-sulfonylenamine ( 2e ), respectively.     

Synthesis and anti-HIV-1 activity of 1,5-dialkyl-6-(arylselenenyl)uracils and -2-thiouracils

The 1,5-dialkyl-6-(arylselenenyl)uracils 10a-h and -2-thiouracils 10i-p have been synthesized as potential anti-HIV-1 agents. Cyclization of N-alkyl-N'-[3,3-di(methylthio)-2-alkylacryloyl]ureas 6a-d and -thioureas 6e-h in acetic acid either containing a catalytic amount of methanesulfonic acid at 80°or containing 1 equivalent of methanesulfonic acid at room temperature afforded 1,5-dialkyl-6-(methylthio)uracils 7a-d in 84–96% yields and 1,5-dialkyl-5,6-dihydro-6,6-di(methylthio)-2-thiouracils 11a-d in 88–99% yields, respectively. Oxidation of 7a-d and 11a-d with either 3-chloroperoxybenzoic acid in benzene or aqueous sodium periodate solution in methanol gave 1,5-dialkyl-6-(methylsulfonyl)uracils 8a-d in 88–98% yields and 1,5-dialkyl-6-(methylsulfinyl)-2-thiouracils 12a-d in 57–73% yields, respectively, which were subsequently treated with arylselenol 9a-b in ethanolic sodium hydroxide solution to afford 10a-p in 6099% yields. Of these compounds, 6-[(3,5-dimethylphenyl)selenenyl]-5-isopropyl-1-(3-phenylpropyl)uracil ( 10h ) inhibited HIV-1 replication in MT-4 cells at a 50% effective concentration (EC₅₀) of 0.0006 μM with a selective index of 44833, which is 7.7-fold more potent than AZT.     

Controlling both ground- and excited-state thermal barriers to Bergman cyclization with alkyne termini substitution

The cross-coupling reaction of 2,3-dibromo-5,10,15,20-tetraphenylporphyrin with corresponding organostannanes in the presence of a Pd0 catalyst in THF at reflux temperature yields free base 2,3-dialkynylporphyrins 1a,c-e. The subsequent deprotection of trimethylsilyl group of 1a with TBAF in THF under aqueous conditions produces the 2,3-diethynyl-5,10,15,20-tetraphenylporphyrins 1b in 87% yield. Compounds 1a-d undergo zinc insertion upon treatment with Zn(OAc)2.2H2O in CHCl3/MeOH to give zinc(II) 2,3-dialkynyl-5,10,15,20-tetraphenylporphyrins (2a-d) in 70-92% yields. Thermal Bergman cyclization of 1a-e and 2a-d was studied in chlorobenzene and approximately 35-fold 1,4-cyclohexadiene at 120-210 degrees C. Compounds 1b and 2b with R = H react at lower temperature (120 degrees C) and produce cyclized products 3b and 4b in higher yields (65-70%) than their propyl, isopropyl, and phenyl analogues, with R = Ph being the most stable. Continuing in this trend, the -TMS derivatives 1a and 2a exhibit no reactivity even after heating at 190 degrees C in chlorobenzene/CHD for 24 h. Photolysis (at lambda >/= 395 nm) of 1b and 2b at 10 degrees C leads the formation of isolable picenoporphyrin products in 15 and 35% yields, respectively, in 72 h, whereas these compounds are stable in solution under same reaction conditions at 25 degrees C in the dark. Unlike thermolysis at 125 degrees C, which did not yield Bergman cyclized product for R = Ph, photolysis generated very small amounts of picenoporphyrin products (3c: 5%; 4c: 8% based on 1H NMR) as well as a mixture of reduced porphyrin products that were not separable. Thus, trends in the barrier to Bergman cyclization in the excited state exhibit the same trend as those observed in the ground state as a function of R-group. Finally, photolysis of 2b at 10 degrees C with lambda >/= 515 or 590 nm in benzene/iPrOH (4:1, 72 h) produces 4b in 15 and 6% isolated yields, indicating that conjugation of the enediyne unit into the porphyrin electronic transitions leads to sufficient distortion to generate photoproduct even with long wavelength excitation.     

Novel extension of Meyers' methodology: stereoselective construction of axially chiral 7,5-fused bicyclic lactams

A novel extension of Meyer's lactamization is reported for the preparation of seven-membered ring lactams 1a-d incorporating a biaryl unit. The required keto-esters 2a-c were readily accessible via the Suzuki coupling reaction. A borylation-Suzuki coupling (BSC) sequence was successfully developed for the high-yielding preparation of keto-ester 2d. Cyclization of the resulting keto-esters 2a-d or keto-acids 5a,c,d in the presence of (R)-phenylglycinol afforded the desired lactams 1a-d in high yields (72-93%) and excellent diastereoselectivities (>95%). This methodology provides a facile stereoselective access to new axially chiral bridged biaryls.     

NaOH-catalyzed thiolysis of alpha,beta-epoxyketones in water. A key step in the synthesis of target molecules starting from alpha,beta-unsaturated ketones

NaOH (0.02-0.3 molar equiv) is an efficient catalyst for the thiolysis reactions of alpha,beta-epoxy ketones with alkyl and aryl thiols in water. Thiolysis of 3,4-epoxyheptan-2-one (1) with thiols 2a-d has been accomplished in mild conditions (30 degrees C and pH 6 or 9) with complete C-alpha-regioselectivity and anti-stereoselectivity, and the corresponding anti-beta-carbonyl-beta-hydroxysulfides 3a-d have been prepared in excellent yields (95-98%). Compounds 3a-d, depending on their nature and pH conditions, have undergone dehydration, C-3 epimerization reaction, and retroaldol condensation. Dehydration of anti-3a-d has been chemoselectively carried out by in situ acidic treatment at 70 degrees C, giving stereoselectively the related (Z)-vinyl sulfides 4 in 89-94% overall yields. Under NaOH-catalyzed thiolysis conditions, cyclic alpha,beta-epoxyketones 6-9 have shown C-alpha attack only and spontaneously dehydrated to furnish the corresponding vinyl sulfides in high yields (90-96%). The reactions of calchone oxide (10) with thiols 2b-d have exclusively resulted in the formation of beta-carbonylsulfides 10b-d (82-93% yield), coming from the nucleophilic attack at the alpha-position and retroaldol condensation. To highlight the synthetic utility of this procedure, one-pot multisteps preparation of vinyl sulfides 7b and 7c, vinyl sulfoxides 12 and 13, and 1,5,6,7-tetrahydro-4H-1,2,3-benzotriazol-4-one (14) starting from 2-cyclohexen-1-one (11) have also been reported.     

Highly selective addition of chiral,sulfonimidoyl substituted bis(allyl)titanium complexes to N-sulfonyl alpha-imino esters: asymmetric synthesis of gamma,delta-unsaturated alpha-amino acids bearing a chiral,electron-withdrawing nucleofuge at the delta-position

Selective addition of the chiral, sulfonimidoyl substituted bis(allyl)titanium complexes 5a-d, which are configurationally labile in regard to the Calpha-atoms, to N-toluenesulfonyl (Ts)-, N-2-trimethylsilylethanesulfonyl (SES)-, and N-tert-butylsulfonyl (Bus) alpha-imino ester (9a-c) in the presence of Ti(OiPr)(4) and ClTi(OiPr)(3) afforded with high regio- and diastereoselectivities in good yields the (syn, E)-configured beta-alkyl-gamma,delta-unsaturated alpha-amino acid derivatives 2a-g, which carry a chiral, electron-withdrawing nucleofuge at the delta-position and a cyclohexyl, an isopropyl, a phenyl, and a methyl group at the beta-position. Addition of the cyclic bis(allyl)titanium complex 14 to N-Bus alpha-imino ester 9c afforded with similar high regio- and diastereoselectivities the (E)- and (Z)-configured amino acid derivatives (E)-8 and (Z)-8. Reaction of complexes 5a-d with alpha-imino esters 9a-c in the presence of Ti(OiPr)(4) occurs stepwise to give first the mono(allyl)titanium complexes containing 2a-g as ligands, which react in the presence of ClTi(OiPr)(3) with a second molecule of 9a-c with formation of two molecules of 2a-g. Formation of (S,R,E)-configured homoallylic amines 2a-g entails Si,Re,E processes of alpha-imino esters 9a-c with the (R,R)-configured bis(allyl)titanium complexes (R,R)-5a-d and (R)-configured mono(allyl)titanium complexes (R)-17a-d, both of which are most likely in rapid equilibrium with their (S,S)-diastereomers and (S)-diastereomers, respectively. Interestingly, in the reaction of 5a-d with aldehydes, the (S,S)-configured complexes (S,S)-5a-d are the ones which react faster. Reaction of the N-titanated amino acid derivatives Ti-2a and Ti-2b with N-Ts alpha-imino ester 9a led to the highly diastereoselective formation of imidazolidinones 15a and 15b, respectively. Cleavage of the sulfonamide group of the N-Bus amino acid derivative 2d with CF(3)SO(3)H gave quantitatively the sulfonimidoyl functionalized amino acid H-2d. A Ni-catalyzed cross-coupling reaction of the amino acid derivative 2e with ZnPh(2) led to a substitution of the sulfonimidoyl group by a phenyl group and furnished the enantiomerically pure protected alpha-amino acid Bus-1. Two new N-sulfonyl alpha-imino esters, the SES and the Bus alpha-imino esters 9b and 9c, respectively, have been synthesized from the corresponding sulfonamides by the Kresze method in medium to good yields. The N-SES alpha-imino ester 9b and the N-Bus alpha-imino ester 9c should find many synthetic applications, in particular, in cases where the N-Ts alpha-imino ester 9a had been used before.     

Syntheses of the first N-mono- and N,N'-dipolyfluoroalkyl-4,4'-bipyridinium compounds

Reactions of 4,4'-bipyridine (1) with excess of polyfluoroalkyl iodides (2a-d) at 100-110 degrees C, under neat conditions, led to the formation of monoquaternary salts (3a-d) in > 90% yields. Salts 3a-d were metathesized with LiN(SO2CF3)2 either in water or water/acetone mixtures to form ionic liquids (4a-d), respectively, in > 88% yields. When 1 was reacted with 2.5 equivalent of 2a-c in DMF at 110 degrees C, the diquaternary salts 5a-c were formed in > 85% yields. Alternatively, 5a-c were also synthesized by heating a mixture of 3a-c and 2a-c (1.25 equivalent) in DMF. The metathesis reaction of 5a-c with LiN(SO2CF3)2 produced dicationic ionic liquids (6a-c) in > 86% yield.     

Synthesis of novel 4(5)-(5-aminotetrahydropyran-2-yl)imidazole derivatives and their in vivo release of neuronal histamine measured by brain microdialysis

The (2R,5S)-trans- and (2S,5S)-cis-stereoisomers 1a and 1b of 4(5)-(5-aminotetrahydropyran-2-yl)imidazole, which have two chiral centers and adopt a stable chair conformation, were synthesized via cyclization of diol intermediates 7 using L-glutamine as the starting material. Their enantiomers, (2S,5R)-trans-1c and (2R,5R)-cis-1d, were synthesized by the same methodology from D-glutamine. Stereo isomers 1a-d were converted into cyanoguanidines 11a-d, and into N-isopropyl and N-3,3-dimethylbutyl derivatives 12a-d and 13a-d, respectively. The results of in vivo brain microdialysis of the derivatives apparently indicated that only (2S,5R)-isomers increased the release of neuronal histamine. Among the many (2S,5R)-N-alkyl derivatives, 13c (OUP-133) and 18 (OUP-153) increased histamine release to 180-190% and 180-200% of basal levels, respectively, and were found to be novel histamine H(3) antagonists.     

beta-acylvinyl anion and dianion equivalents: lithiation of 1-[(2EZ)-3-chloroprop-2-enyl]-1H-1,2,3-benzotriazole: preparation and elaboration of 1-(2-oxiranylvinyl)-1H-benzotriazoles

The allyllithium generated from 1-[(2EZ)-3-chloroprop-2-enyl]-1H-1,2,3-benzotriazole (5) and LDA, in the presence of HMPA, reacts with enolizable and nonenolizable carbonyls solely at the CCl terminus to give 1-(2-oxiranylvinyl)benzotriazoles 6a-g in 61-82% yields. Allyllithiums generated from 6a,c reacted exclusively at the CBt terminus to give 10a-d in 68-88% yields. Acidic hydrolysis of (oxiranylvinyl)benzotriazoles 6a-g and 10a-d provided 4-hydroxyalk-2-en-1-one derivatives 12a,b,c,e,g, 13a-d, and furan 14 in 54-86% yields.     

Synthesis of highly branched sulfur-nitrogen heterocycles by cascade cycloadditions of [1,2]dithiolo[1,4]thiazines and [1,2]dithiolopyrroles

We report the synthesis of some new polysulfur-nitrogen heterocycles by cascade cycloadditions to readily available polycyclic 1,2-dithiole-3-thiones. Thus, treatment of bis[1,2]dithiolopyrrole dithione 1 with dimethyl acetylenedicarboxylate (DMAD) or dibenzoylacetylene (DBA) gave the 1:4 adducts 2a,b and 3a. On the other hand, cycloaddition of bis[1,2]dithiolo[1,4]thiazine dithiones 4a-d with the same dipolarophiles gave the 1:2, 1:3, or 1:4 adducts 5a-c, 6a, 7a, 8a, 9a, and 10a,c,d selectively in fair to high yields. Reaction conditions were crucial for achievement of selectivity in thermal reactions. Catalysis by scandium triflate was used in the reaction of 4a and 2 equiv of DMAD. Treatment of the [1,2]dithiolo[1,4]thiazine dithione 11 with DBA gave the 1:2, 1:3 (two isomers), and 1:4 adducts 12-14 and 15a-d selectively. Cyclic voltammetry of selected examples showed irreversible processes that were not influenced by peripheral groups bonded to the heterocyclic system.     

Asymmetric synthesis of 2-alkyl-perhydroazepines from [5,3,0]-bicyclic lactams

The synthesis and utility of a novel class of [5,3,0]-bicyclic lactams are described. Produced by the cyclodehydration of (R)-phenylglycinol with omega-keto acids, lactams 4-6 were obtained as separable diastereomeric mixtures ( approximately 2:1) in low yields ( approximately 40%). Higher chemical yield (up to 61%) was realized via an alternate route involving ring closure metathesis of 2-allyl-N-acroyl oxazolidines, 8. Stereoselective reductions of the syn-bicyclic lactams, 4a and 5a, occurred with the use of alane or lithiumaluminum hydride, affording azepine alcohols, 11a and 15a, of the R configuration at the 2-position, in good to moderate yields (50-88%). High selectivity was also observed in the diisobutylaluminum hydride reduction of the epimeric anti lactams, 4b and 5b, affording azepine alcohols, 11b and 15b, of the S configuration at C-2. Hydrogenolytic cleavage of the N-benzyl moiety afforded chiral 2-substituted perhydroazepines, (R)- and (S)-12, in good yields and good enantiomeric excesses (84-94%).     

Lithiation of 1-chloromethylbenzotriazole: generation and elaboration of benzotriazolyloxiranes

1-Benzotriazolylchloromethyllithium generated from 1-chloromethylbenzotriazole (1) and LDA reacts with enolizable and nonenolizable ketones to give benzotriazolyloxiranes 2a-g in good yields. The oxiranyllithiums 4a-d generated from 2a-d and n-BuLi at -78 degrees C were trapped by a variety of electrophiles to give oxiranyl derivatives 5a-j in good to excellent yields. Lewis-acid-promoted nucleophilic ring opening of benzotriazolyloxiranes 2a,f,g with allyltrimethylsilane gave the corresponding 1,7-octadien-4-ols 6a-c in 68-75% yield. Hydrolysis of alpha-acylbenzotriazolyloxiranes 5g,h provided 3-hydroxy-1,2-diones 7a and 7b in 73 and 86% yield, respectively.     

Asymmetric [2 + 1] Cycloaddition Reactions of 1-Seleno-2-silylethene

The reaction of (E)-1-(phenylseleno)-2-(trimethylsilyl)ethene (1) and vinyl ketones 2a-d in the presence of a chiral Lewis acid prepared from TiCl(4), Ti(O(i)Pr)(4), (R)- or (S)-1,1'-binaphthol (BINOL), and MS4A gave enantiomerically enriched cis cyclopropane products 3a-d. The enantiomeric excess and chemical yield varied depending on the ratio of TiCl(4) and Ti(O(i)Pr)(4) to 1. Reproducible results (43-47% ee/33-41% yields) for cis-1-acetyl-2-[(phenylseleno)(trimethylsilyl)methyl]cyclopropane (3a) were obtained using 1.1 equiv of TiCl(4), 0.54-0.65 equiv of Ti(O(i)Pr)(4), and 1.65 equiv of BINOL. The observed enantioselectivity was explained by consideration of the structure of the postulated intermediates, alkoxy titanium-carbonyl complexes, via ab initio MO calculations.     

Preparation of 1,5-disubstituted 4-sulfonylpyrazoles, β-cyano-β-sulfonylenamines and 5-substituted 4-sulfonylisoxazoles from β-keto-β-sulfonylenamines

Reaction of β-keto-β-sulfonylenamines 1a,b with N-substituted hydrazines gave 1,5-disubstituted 4-sulfonylpyrazoles 2a-h in moderate yields, which were ring-opened on treatment with n-butyllithium to afford β-cyano-β-sulfonylenamines ( 3a,b,d-f ). 5-Substitued 4-sulfonylisoxazoles 6a-d were also prepared from 1a-d and hydroxylamine.