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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.Key words: enolate conformation, pi-stacking, 2-phenylcyclohexanol, chiral auxiliary.

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.

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.

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.

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.

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.

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.

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.

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.

Reaction of tributyltin hydride with a variety of organic sulfides gives results which depend on the structure of the starting material. Acyclic sulfides undergo desulfurization leading to hydrocarbons in varying yields. However, 2,5-dihydrothiophenes give dienes and 3,6-dihydro-2H-thiopyrans are inert.

2,5-Dihydrothiophenes are dehydrogenated to thiophenes in high yield using chloranil in tert-butanol or pyridine. The presence of a fully substituted carbon atom blocks the reaction. The method allows a flexible regiospecific synthesis of thiophenes in high yield from readily available starting materials.

The addition of iodine azide to 2-cyclopentenone led to the formation of 2-iodo-2-cyclopentenone. A similar reaction with 2-cyclohexenone afforded the expected addition products in addition to 2-iodo-2-cyclohexenone.