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Alkylation of the hippurate esters of trans 2-(p-substituted phenyl)cyclohexanol with benzyl bromide affords phenylalanine derivatives in high chemical yield. The reaction stereoselectivity varies from 20 to >98% depending on the aromatic group in the cyclohexyl auxiliary. A model that correctly predicts the sense of the induction is proposed.

Nimesulide is a nonsteroidal anti-inflammatory drug recently detected in equine blood and urine samples taken at the race track. The detection of the drug in a blood sample led to the identification of an unknown thin-layer chromatographic (TLC) spot in track urine samples as a metabolite of nimesulide. Characterization of the unknown TLC spot and comparison with the synthesized compound shows that the unknown TLC spot is a previously unreported equine metabolite of nimesulide. The metabolite was identified as resulting from the reduction of the nitro group on nimesulide to an amino group. This reduced nitro metabolite (4-amino-2-phenoxy-methanesulfonanilide) is a major metabolite of nimesulide in the equine.

Benzylation of chiral esters of N-acylglycines using various bases and additives was examined. No C-alkylation was observed with one equivalent of base. Diastereoselectivities were dependent on the amount of additive, the nature of the N-acyl group, and the chiral ester. A model to account for the degree and sense of the stereoselectivity is proposed.

Alkylations of anions derived from dipeptides with a glycine at the C-terminus have been investigated. A hydrocarbon sedition in the N-terminal residue does impart some asymmetric induction. The use of a chiral ester derivative provides the potential for double asymmetric induction and good selectivity. With an aspartyl residue at the N-terminus, problems were encountered due to competing side reactions. The use of an azetidinone could circumvent some of these, but the observed induction was not high.

The trimethylsiyl ether 7 derived in two steps from camphor underwent ring expansion via an acylion rearrangement to afford two products (8 and 9) when desilylation was attempted. Compound 9 was stable but 8 was oxidized in air to homocamphoric acid anhydride 11. Key words: camphor, acyloin rearrangement.

Alkylations of anions derived from dipeptides with a glycine at the C-terminus have been investigated. A hydrocarbon sedition in the N-terminal residue does impart some asymmetric induction. The use of a chiral ester derivative provides the potential for double asymmetric induction and good selectivity. With an aspartyl residue at the N-terminus, problems were encountered due to competing side reactions. The use of an azetidinone could circumvent some of these, but the observed induction was not high.

Contrary to a published report, C-alkylation of methyl hippurate requires two equivalents of base. The choice of additive (TMEDA or HMPA) influences the result. Deuteration of the enolate gives results which depend on both the deuterium source and the nature of the additive.

The trimethylsiyl ether 7 derived in two steps from camphor underwent ring expansion via an acylion rearrangement to afford two products (8 and 9) when desilylation was attempted. Compound 9 was stable but 8 was oxidized in air to homocamphoric acid anhydride 11. Key words: camphor, acyloin rearrangement.

Dissolving metal reduction of known enone S affords predominantly the racemic form of title ketone ( 3 ) whereas catalytic reduction gives the meso isomer 6 . Neither ketone 3 nor alcohol 4 could be satisfactorily resolved. Asymmetric synthesis of (−)− 3 and (+)− 4 (ee=91 %) was effected from ketone (+)- 13 .

(x unspecified) [54287-50-2] C4H8O5S (MW 168.19) (x = 1) [20769-58-8; 35346-47-5] C4H8O8S2 (MW 248.26) InChI = 1S/C4H8O2.O3S/c1-2-6-4-3-5-1;1-4(2)3/h1-4H2; InChIKey = HGBGABMSTHQFNJ-UHFFFAOYSA-N (x = 2) [52922-31-3] C4H8O11S3 (MW 328.33) InChI = 1S/C4H8O2.2O3S/c1-2-6-4-3-5-1;2*1-4(2)3/h1-4H2;; InChIKey = NTHGLQVCZIRQNS-UHFFFAOYSA-N (x = 3) [52922-32-4] InChI = 1S/C4H8O2.3O3S/c1-2-6-4-3-5-1;3*1-4(2)3/h1-4H2;;; InChIKey = VZBNWRDNLDRWOZ-UHFFFAOYSA-N (useful for effecting Beckmann rearrangements;8 sulfonation of alkenes11 and arenes16) Physical Data: mp 75 °C,2 but almost never isolated. Solubility: generated as a solution in dioxane, with or without other solvents. Preparative Methods: the Organic Synthesis procedure2 involves reaction of Sulfur Trioxide (as Sulfan B) with dioxane in 1,2-dichloroethane. The complex precipitates and is used immediately. An alternate procedure involves treatment of dioxane with ClSO3TMS,3 itself prepared by reaction of Chlorotrimethylsilane and Chlorosulfonic Acid.4 Handling, Storage, and Precautions: reacts vigorously with water, alcohols, etc. It has been reported to decompose violently upon standing at rt2 or upon heating to 75 °C.5 The chemistry is essentially that of SO3 with some attenuation in reactivity. Safety precautions in the handling of SO3, which can be an unexpectedly strong oxidant, should be followed.1c

The preparation of S-(−)-6-methyl-2-piperidinone from S-alanine and R-(−)-5-methyl-2-pyrrolidinone from S-glutamic acid and their conversion into S-2-methyl-1-azoniatricyclo[4.4.4.01,6]tetradecane (2a) and R-2-methyl-1-azoniatricyclo-[4.4.3.01,6]tridecane (2b) with enantiomeric excesses of 95 and 92% respectively are described. The use of these compounds as phase-transfer catalysts did not lead to significant asymmetric induction.

Oxidation of 1,3-oxathiolan-5-ones (1) gives acceptable yields of sulfoxides only when C4 is unsubstituted. Sulfoxides derived from 1,3-thiazolidine-4-ones (8) are easily prepared. Acid-catalyzed rearrangement in the presence of 1-alkenes or benzene leads to alkylation (arylation) at C5. Alkylation of 8c may be generally more effective than that of 1. An aldol condensation of 8c shows little stereoselectivity.

Alkylation of the D-camphor imine of tert -butyl glycinate with secondary allylic and benzylic halides affords products which have high stereochemical purity, particularly at the halogen displacement site.

The preparation of a series of vinyltriphenylphosphonium salts, all of which bear a substituent on the carbon attached to phosphorus, is described. Yields are generally poor unless a symmetrical secondary allylic halide can be used. The use of these salts in the preparation of substituted 2,5-dihydrothiophenes has been examined. In general, reaction times are increased and product yields decreased relative to the reactions of the unsubstituted salts previously reported. This result is ascribed to steric inhibition of the intramolecular Wittig reaction.

La trimethyl-2,2,4 oxathiolanne-1,3one-2 (A) est alkylee en 4 par des halogenures d'alkyle en presence de LDA/HMPT; la dimethyl-2,2,4 oxathiolanne-1,3one-2 (B) ne donne pas de produit d'alkylation. Les deux composes A et B donnent des produits d'aldolisation diastereoisomeres avec des aldehydes et cetones et des produits d'addition 1,2 ou 1,4 avec la cyclohexene-2one ou la butene-3one-2

Distillation of ω-carboxyalkyl lactams from soda-lime leads to the formation of bicyclic enamines or imines with concomitant loss of carbon dioxide and water. Monoamides of dicarboxylic acids afford cyclic ketones. A mechanistic rationale is presented and it is concluded that the reaction is a variant of the classical Ruzicka cyclization of dicarboxylic acids. The method allows the regiospecific formation of iminium salts of bicyclic nitrogen heterocycles.

The use of 3-carboxylated 2,5-dihydrothiophenes as the dienophilic component of the Diels–Alder reaction has been investigated. The yields are generally quite low. The formation of conjugated dienes that are aminated at an interior position of the conjugated chain by formation and thermal decomposition of 3-acetamido-2,5-dihydrothiophenes appears to be a viable route to these useful compounds. One example of the Diels–Alder reaction of 2-carboxylated diethyl vinylphosphonates is reported.

The rationale for considering 1-azoniapropellane salts as potential chiral phase-transfer catalysts is presented. The synthesis of two examples of these types of molecules is outlined and their efficacy in phase-transfer catalyzed reactions is established.

Vinylphosphonates 11, readily prepared from diethyl carbomethoxymethyl phosphonate (10) react with α-mercaptocarbonyl compounds to afford substituted 3-carbomethoxy-2,5-dihydrothiophenes in excellent yields. The scope of this synthesis is indicated and the use of the products in the synthesis of substituted 2-carboxy-1,3-butadienes is illustrated.

Regiospecific formation of 10-allyl-1-ketoquinolizidine (7) is achieved in high yield by a [2.3] sigmatropic rearrangement of N-allyl-1-ketoquinolizidinium bromide (6). Wolff–Kischner reduction of 7 affords 10-allylquinolizidine (8) contaminated by the 10-propyl and 10-ethynyl analogs in amounts which depend on the reaction conditions. The carbon-13 spectrum of 8 indicates a trans-fused ring system with an axial substituent at C-10.

The reaction of α-mercaptoaldehydes and ketones with 1,3-butadien-1-yltriphenylphosphonium salts (4) unexpectedly leads to 3-vinylthiophenes and triphenylphosphine. This result is attributed to the retardation of the usual Wittig cyclization reaction which allows the competing reaction to occur.

The complete carbon-13 nmr spectra of 16 alkylated 2,5-dihydrothiophenes and 10 sulfones derived from them are reported. No significant interactions between C-2 substituents and C-5 are noted and stereochemical determinations based on this γ effect are not possible. On oxidation to the sulfones, C-2 and C-5 are dramatically deshielded but C-3 and C-4 are shielded. A possible explanation for this effect is presented.

L'exces diastereoisomere est relie a la densite d'electrons π et aux effets steriques dans l'electrophile

The alkylation of the sodium, potassium, zinc, and zirconium enolates of the R-camphor imine of tert-butyl glycinate have been examined and the stereochemical results compared with those obtained with the lithium enolate. No difference was noted for the sodium enolate but inferior chemical yields and stereoselectivities were obtained with the potassium enolate, perhaps due to its increased ionic character. Substituting TMEDA for HMPA in these reactions led in all but one case to reduced stereoselectivities. The results support and are interpreted in terms of the π–metal association model previously proposed.

The preparation of 2-carboxylated-1,3-dienes from carbomethoxy vinylphosphonates and 2-mercaptocarbonyl compounds has been shown to give stereoisomeric mixtures. This may be due to the formation of stereoisomers of the intermediate 2,5-dihydrothiophenes and (or) to the occurrence of both modes of disrotatory sulfur dioxide elimination.

An improved synthesis of 1-azoniatricyclo[4.4.3.0 1,6 ]tridecane ( 2 ) and the preparation of the remaining member of the series, 1-azoniatricyclo[4.3.3.0 1,6 ]dodecane salts ( 3 ) have been achieved. Using a combination of 1 H (at 400 MHz) and 13 C NMR spectra has allowed the assignment of the signals in the well-resolved 1 H spectra. The results indicate that 1 exists in the all-chair form which undergoes racemization by ring inversion with a rate constant of 0.7 sec − and further that the counterion in these salts is restricted to associating with only one face of the tetrahedral N atom.

Alkylation of the (R)-camphor imine of tert-butyl glycinate with a variety of alkylating agents gave diastereoselectivities ranging from 0–100%. Simple alkyl halides larger than methyl give de's (diastereomeric excesses) of ca. 50% whereas those derived from allylic type systems afford de's of 75–100%. The results are best explained by invoking a transition state interaction between the π system of the alkylating agent and the imine which, for steric reasons, requires alkylation to occur from the pro-R face.

The crystal structures of 1-azoniatricyclo[4.4.4.01,6]tetradecane bromide (1) and 1-azoniatricyclo[4.4.3.01,6]tridecane bromide (2) are reported. Compound 1, C13H24NBr, crystallizes in space group P63/mmc with a = 8.383(2) Å, c = 10.092 Å, γ = 120°, Z = 2. Compound 2, C12H22NBr, crystallizes in space group P63/mmc with a = 8.283(2) Å, c = 10.046(2) Å, γ = 120°, Z = 2. The crystal structures of 1 and 2 are statistically disordered with both enantiomers occurring in the unit cell. Compound 2 is further disordered with the one five-membered ring and the two six-membered rings of the cation being averaged over the same site in the unit cell.The structures confirm the previously reported conclusions based on the 400 MHz nmr spectra of 1.

Attempted imine formation between 3-hydroxycamphor and tert. butyl glycinate led to 8 the substitution product at the 3-position. Zinc-acetic acid treatment of 8 afforded 3-acetoxycamphor. Alkylation of the imine from from norcamphor and tert. butyl glycinate gave no stereoselection. Alkylation of the imine from from 10-hytdroxymethylcamphor and tert. butyl glycinate gave stereoselectivities inferior to those obtained from the imine of camphor itself ( 1 ) but aldol condensation with benzaldehyde, a reaction not possible with 1, was affected in 71% yield.

In the presence of an allylic bromide, aldehydes, but not ketones, react with cyanide ion under phase-transfer catalysis to give cyanohydrin allyl ethers which can be converted to ketones. Other alkylating agents and nucleophiles give different results. Replacing the allylic bromide with acetic anhydride leads to cyanohydrin acetates.

Formolysis of 1,5-cyclooctadiene monoepoxide (1) has been shown to give only ca. 25% of products of transannular reactions. The difference between this result and those from the solvolyses of cyclooctene oxide and 4-cyclooctenyl brosylate is attributed to conformational and ring-strain effects.

Dipole moments are reported for trimethylene sulfite and 11 alkyl derivatives in a variety of solvents (C6H12, CCl4, C6H6, dioxan). The variation of dipole moment with solvent for one of the 5-t-butyltrimethylene sulfite isomers is confirmed, but this behavior is not shown by the other compounds. This latter fact is used to rule out rapid chair–chair interconversion for these compounds. Recent ultrasonic absorption experiments are reinterpreted in the context of vicinal electron pair interactions and their effect on conformational analysis of sulfites and similar six-membered compounds. The result is a general scheme which is consistent with available information and which we believe is preferable to analysis of these compounds by analogy with cyclohexane.

Reinvestigation of the acetolysis of 5,5-diphenylcyclononyl tosylate (1) has confirmed the absence of any transannular processes and deamination of the corresponding amine 16 gave a similar resuit. Trifluoroacetolysis of 1 caused extensive transannular hydride migration but no phenyl migration. The former may be due to secondary acid-catalyzed rearrangements.

Using the reaction between four representative vinylphosphonium salts and three α-mercaptoaldehydes, 12 3,4-unsubstituted 2,5-dihydrothiophenes(1) were prepared. The reaction proceeds in excellent yields under mild conditions. The use of these compounds in the synthesis of dienes is indicated.