Electrocyclic reactions : Stereochemistry of the triene electrocyclization

Four trienes of known stereochemistry have been prepared and their thermal cyclization studied to ascertain the general stereochemistry of thermal triene electrocyclic reactions. A mixture containing (Z)-1,2-dicyclohexenylethylene was obtained by semihydrogenation. Spectra evidence for thermal cyclization of the triene was obtained, but inability to isolate pure materials canceled plans for stereochemical study.A stereoselective synthesis for (E,Z,E)-2,4,6-octatriene was devised and a pure sample was cyclized thermally to give a 5,6-dimethylcyclohexadiene. Oxidative cleavage of this diene gave meso-2,3-dimethylsuccinic acid. Pure samples of (Z,Z,E)- and (Z,Z,Z)-2,4,6-octatrienes were prepared and found to interconvert thermally at 110°. Cyclization of the equilibrium mixture occurred at 178° to give a 5,6-dimethylcyclohexadiene which gave rac-2,3-dimethylsuccinic acid upon oxidative cleavage. Evidence is presented to suggest that the (E,Z,Z) isomer is the actual reactant undergoing cyclization. Both cyclohexadienes were shown to undergo a 1,5-hydrogen shift to form 1,6-dimethyl-1,3-cyclohexadiene.Rates of the electrocyclic reactions were measured in pentane solution, and thermodynamic activation parameters were ascertained. The results are: (E,Z,E) k(132°) = 4·45 × 10^?5 sec^?1, ΔH

= 28·6 kcal/mole and ΔS

= ?7 eu; (E,Z,Z)+(Z,Z,Z) k(178°)= 1·53 × 10^?5 sec^?1 or (E,Z,Z) k(178°) = 2·13 × 10^?5 sec^?1, ΔH

= 32 kcal/mole, ΔS

= ?9 eu; cis-5,6-dimethyl-1,3-cyclohexadiene (1,5-H shift), k(178°) = 1·77 × 10^?5 sec^?1, ΔH

= 33 kcal/mole, ΔS

= ?7 eu; trans-5,6-dimethyl-1,3-cyclohexadiene (1,5-H shift), k(178°) = 7·7 × 10^?6 sec^?1, ΔH

= 36 kcal/mole, ΔS

= ?3 eu.     

Hochdruckversuche—IX: Die thermische isomerisierung von 1,2-diphenyl-3-methyl-cyclobuten-(1)-cis-3,4-dicarbonsäuredimethylester und 3,4-dimethyl-1,2-diphenyl-cyclobuten-(1)-cis-3,4-dicarbonsäuredimethylester

Dimethyl-1,2-diphenyl-3-methyl-cyclobutene-(1)-cis-3,4-dicarboxylate 2 leads in a thermal reaction to an equilibrium with (E, Z)-dimethyl-3,4-diphenyl-5-methyl-muconate (4). The equilibrium is shifted to the cyclic compound by pressure. Dimethyl-3,4-diphenyl-cyclobutene-(1,2-diphenyl-cyclobutene-(1)-cis-3,4-dicarboxylate (3) isomerizes thermally to (E, Z)-dimethyl-2,5-dimethyl-3,4-diphenylmuconate (6). Both reactions are accelerated by pressure. The activation volumes ΔV₀⁺ are given for each ringopening reaction.     

Synthesis and Chiroptical Properties of Dimethyl 8,12-Diphenylbenzo[d]heptalene-6,7-dicarboxylate

6,10-Diphenylbenz[a]azulene ( 3 ) was reacted with dimethyl acetylenedicarboxylate (ADM) in the presence of 2 mol-% of [RuH₂(PPh₃)₄] in MeCN at 100° to yield a 7:1 mixture of dimethyl 2,6-diphenyl-9,10-benzotricyclo[6.2.2.0^1,7]dodeca-2,4,6,9,11-pentaene-11,12-dicarboxylate ( 4 ) and dimethyl 8,12-diphenylbenzo[d]heptalene-6,7-dicarboxylate ( 5 ; Scheme 2). The tricycle 4 , when heated in DMF at 150° for 1 h led to the formation of 81.5% of the heptalene-6,7-dicarboxylate 5 and 15% of the starting azulene 3 . No rearrangement of tricycle 4 was observed, when it was heated at temperatures up to 180° in pseudocumene. The heptalene-6,7-dicarboxylate 5 was easily separated into its antipodes (PM)-and (MP)- 5 on a Chiracel column (cf. Fig. 2). On heating at 150° for 1 h, (MP)- 5 showed no racemization at all. The Ru-catalyzed reaction of benz[a]azulene ( 6 ) with ADM led to the formation of dimethyl 9,10-benzotricyclo[6.2.2.0^1,7]dodeca-2,4,6,9,11-pentaene-11,12-dicarboxylate ( 7 ; Scheme 3). However, the formation of the corresponding heptalene-6,7-dicarboxylate could not be observed.     

Relative reactivities of 1,2-cyclohexadiene with conjugated dienes and styrene

Generation of 1,2-cyclohexadiene in the presence of conjugated dienes leads to (2 + 2) and/or (2 + 4) cycloaddition products. Methods used to generate 1,2-cyclohexadiene were: (1) treatment of 6,6-dibromobicyclo[3.1.0]hexane with methyllithium in tetrahydrofuran-ether at 0° and 60°; (2) treatment of 1,6-dichlorocyclohexene with magnesium in tetrahydrofuran at 60°; and (3) treatment of 1-bromocyclohexene with t-BuOK in THF at 60° or dimethyl sulfoxide at 40°. Comparison of relative reactivities with various dienes and styrene in ether solvents at 60° confirmed that the same intermediate, uncomplexed 1,2-cyclohexadiene, was involved in these reactions. Relative reactivities at 0° and 60° were found to be: 2-methylfuran (0·12, 0·14); furan (0·17, 0·16); 2,4-hexadiene (0·17,—); cis-pentadiene (0·53, 0·53); 2,3-dimethylbutadiene (2·35, 1·9); 1,3-cyclohexadiene (1·85,—); styrene (2·35, 1·9); and 1,3-cyclopentadiene (47, 14).     

The reactive states of ions: Octatrienes and dimethyl substituted cyclohexadienes

The principal decomposition routes of molecular ions of cis, cis, cis-2,4,6-octatriene, cis, cis, trans-2,4,6-octatriene, trans, cis, trans-2,4,6-octatriene, trans-5,6-dimethyl-1,3-cyclohexadiene and cis-5,6-dimethyl-1,3-cyclohexadiene were studied using ion kinetic spectroscopy. The loss of radicals from [M]⁺· appears to proceed via a ground state, while loss of a neutral molecule appears to involve either complete equilibration of structure within the system or both ground state and excited state pathways.     

A systematic study of stereochemical effects in homologous poly(alkenamer)s: Dewar benzene versus norbornene

Two diastereomeric derivatives of norbornene, dimethyl (1R,2R,3S,4S)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate and dimethyl (1R,2S,3S,4S)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate, were synthesized and polymerized using ring-opening metathesis polymerization (ROMP). For comparative purposes, diastereomeric derivatives of Dewar benzene, dimethyl (1R,2S,3R,4S)-bicyclo[2.2.0]hex-5-ene-2,3-dicarboxylate and dimethyl (1R,2S,3S,4S)-bicyclo[2.2.0]hex-5-ene-2,3-dicarboxylate, were also synthesized and polymerized using ROMP. The polymerization reactions proceeded in a controlled manner as evidenced in part by linear relationships between the monomer-to-catalyst feed ratios and the molecular weights of the polymer products. Chain extension experiments were also conducted which facilitated the formation of block copolymers. Although the poly(norbornene) derivatives exhibited glass transition temperatures that were dependent on their monomer stereochemistry (cis: 115°C vs. trans: 125°C), more pronounced differences were observed upon analysis of the polymers derived from Dewar benzene (cis: 70°C vs. trans: 95°C). Likewise, microphase separation was observed in block copolymers that were prepared using the diastereomeric monomers derived from Dewar benzene but not in block copolymers of the norbornene-based diastereomers. The differential thermal properties were attributed to the relative monomer sizes as reducing the distances between the polymer backbones and the pendant stereocenters appeared to enhance the thermal effects.     

Reactions of triphenylbenzylphosphonium and tetraphenylstibonium chlorides with potassium tetrachloroplatinates in dimethylsulfoxide

Platinum complexes [Ph₃PhCH₂P]⁺[(Me₂S=O)PtCl₃]^? I and cis-Cl₂(Ph₃Sb)(Me₂S=O)Pt II were synthesized by reaction of triphenylbenzylphosphonium and tetraphenylstibonium chlorides with potassium tetrachloroplatinate in DMSO. Crystal I is formed by triphenylbenzylphosphonium tetrahedral cations [P-C_Ph 1.791(4)-1.795(4) Å, P-C_Alk 1.811(4) Å; CPC 107.57(18)°-111.46(17)°] and by square anions [(Me₂S=O)PtCl₃]^? [Pt-Cl 2.3236(11), 2.2981(12), 2.2977(11) Å; Pt-S 2.1950(10) Å; trans-angles SPtCl 177.51(4)°, ClPtCl 178.74(4)°]. In a square-planar complex II [trans-angles SPtCl 178.01(6)°, ClPtSb 177.96(4)°] with central platinum atom the chlorine atoms [Pt-Cl 2.308(1), 2.350(1) Å], triphenylstibine [Pt-Sb 2.5118(4) Å] and dimethyl sulfoxide [Pt-S 2.195(1) Å] molecules are coordinated. Compound II is a first example of mixed ligand complex of platinum(II), where in the coordination sphere of central atom the tertiary stibine is present along with DMSO ligand.     

Organometallic compound with Lewis base—IV : Dimerization of methyl crotonate by aluminum alkyl-tertiary amine complex

Aluminum alkyl-tertiary amine complex was found to induce the catalytic dimerization of methyl crotonate (MCr) to dimethyl 2-methylpent-4-ene-1,3-dicarboxylate (1) and dimethyl 2-methylpent-cis-3-ene-1,3-dicarboxylate (2). The of the γ-hydrogen of the MCr molecule. Dimer 2 is formed through the isomerization of dimer 1. The complex of AlR₃ with a bidentate ligand, sparteine, produces dimer 1, selectively. The complex of AlR₃ with monodentate ligand NEt₃, on the other hand, induces the isomerization of dimer 1 to the cis-form of dimer 2. The coordination number of aluminum alkyl-tertiary amine complex seems to control the dimerization mechanism of MCr.     

Synthesis and structure of platinum complexes [Ph4P]+[PtCl3(DMSO)]− and [Ph4P]+[PtCl5(DMSO)]−

The reaction of tetraphenylphosphonium chloride with an equimolar amount of potassium tetrachloroplatinate or hexachloroplatinic acid in dimethyl sulfoxide gave the complexes [Ph₄P]⁺[PtCl₃(DMSO)]^? (I) and [Ph₄P]⁺[PtCl₅(DMSO)]^? (II), respectively. The phosphorus atoms in the cations have tetrahedral environment, the CPC angles and P-C distances 105.63(13)°–112.13(14)°, 1.795(3)–1.797(3) Å I) and 105.7(3)°–112.9(3)°, 1.783(7)–1.791(6) Å II). The platinum coordination polyhedra in the anions [PtCl₃(DMSO)]^? and [PtCl₅(DMSO)]^? are distorted square (Pt-S, 2.1937(8); Pt-Cl, 2.2894(10)–2.3024(10) Å; trans-angles: SPtCl, 177.38(4)°; ClPtCl, 175.40(4)°) and octahedron (Pt-S 2.291(2) Å; Pt-Cl, 2.312(2)–2.334(2) Å, trans-angles: SPtCl, 178.28(9)°; ClPtCl, 178.80(9)° and 178.88(8)°).     

Compounds with bridgehead nitrogen. 44—the conformational analysis of perhydropyrido[1,2-c] [1,3]thiazine

The 270 MHz NMR data on trans- and cis-(H-4a, H-7)-7-ethylperhydropyrido[1,2-c][1,3]thiazine show heavy conformational bias to the trans- and S-inside cis-fused conformations, respectively. Comparison of the ¹³C NMR spectra of these anancomeric systems with the ¹³C NMR spectrum of perhydropyrido[1,2-c][1,3]thiazine indicates a trans-?S-inside cis-conformational equilibrium for the latter compound in CDCl₃ at 25°C, containing ca 75% trans-fused conformer. The ¹³C NMR spectrum of perhydropyrido[1,2-c][1,3]-thiazine at ?75°C showed 64% trans-fused conformer and 36% S-inside cis-conformer.     

Thermal Reaction of Azulenes with Dimethyl Acetylenedicarboxylate in Supercritical Carbon Dioxide

1,3,4,6,8-Pentamethylazulene ( 9 ), when heated at 100° in supercritical CO₂ at 150 bar in the presence of 4 equiv. of dimethyl acetylenedicarboxylate (ADM), led to the formation of 16% of a 1:1 mixture of dimethyl 3,5,6,8,10-pentamethylheptalene-1,2-dicarboxylate 12a ) and its double-bond-shifted isomer 12b as well as 4% of the corresponding azulene-1,2-dicarboxylate 13 (Scheme 4). The formation of the [1 + 2] adduct 11 (cf. Scheme 2) was not observed. Similarly, benz[a]azulene ( 25 ) yielded in supercritical CO₂ (150°/170 bar) in the presence of 4 equiv. of ADM dimethyl benzo[d]heptalene-6,7-dicarboxylate ( 29 ; 30%) and dimethyl benzo[a]cyclopent[cd]azulene-1,2-dicarboxylate ( 28 ; 22%; Scheme 5). The reaction of 5,9-diphenylbenz[a]azulene ( 26 ) and ADM in supercritical CO₂ (100°/150 bar) gave the corresponding benzo[d]heptalene-6,7-dicarboxylate 31 (22%) and dimethyl 5,9-diphenyl-4b,10-etheno-10H-benz[a]azulene-11,12-dicarboxylate( 30 ; 25%; Scheme 5).     

Dinuclear rhenium(I) carbonyl complexes based on π-conjugated polypyridyl ligands with tetrathiafulvalenes: Syntheses, crystal structures, properties and DFT calculations

A series of tetrathiafulvalene-substituted 2,3-di(2-pyridyl)quinoxaline (dpq) ligands, 2-(4,5-bis(methylthio)-1,3-dithiol-2-ylidene)-6,7-di(pyridin-2-yl)- [1,3]dithiolo[4,5-g]quinoxaline (L₁), dimethyl-2-(6,7-di(pyridin-2-yl)-[1,3]dithiolo[4,5-g]quinoxalin-2-ylidene)-1,3-dithiole-4,5-dicarboxylate (L₂), and 2-(5,6-dihydro-[1,3]dithiolo[4,5-b] [1,4]dithiin-2-ylidene)-6,7-di(pyridin-2-yl)-[1,3]dithiolo[4,5-g]quinoxaline (L₃), have been prepared. Reactions of these ligands with Re(CO)₅Cl afford the corresponding dinuclear rhenium(I) carbonyl complexes, Re₂(L)(CO)₆Cl₂ (L = L₁, 5a; L = L₂, 5b; L = L₃, 5c). All new compounds are fully characterized by ¹H NMR, IR and mass spectroscopies. The crystal structures of 5a and 5b have been studied. Optimized conformations and molecular orbital diagrams of 5a−5c have been calculated with density functional theory (DFT). The spin-allowed singlet−singlet electronic transitions of all complexes have been calculated with time-dependent DFT (TDDFT), and the UV-Vis−NIR spectra are discussed based on the theoretical calculations.     

Study of thermal decomposition of poly-(vinyl chloride)-type polymers with the use of model substances-V: Pyrolysis of cis-5-chloro-3-heptene and cis- and trans-5-acetoxy-3-heptene in the phase

The gas phase pyrolyses of cis-5-chloro-3-heptene (in the range 267–337°) and cis- and trans-5-acetoxy-3-heptene (300–378°) are homogeneous unimolecular first-order reactions with rate constants given respectively by: log k = (12·03 = 0·13) - (36·2 ± 0·4)/2·303 RT and (12·80 ± 0·11) - (43·0 ± 0·3)/2·303 RT. (Frequency factors in sec^?1 units, activation energies in kcal mol^?1.) No significant differences were found between the rates of decomposition of cis and trans isomers of 5-acetoxy-3-heptene. From the decomposition of these models of poly(vinyl chloride) and poly(vinyl acetate), some conclusions about the role of internal unsaturated groups in the thermal decomposition of both polymers were drawn. The possibility that groups with cis internal double bonds are the most labile structures in a poly(vinyl) chloride macromolecule is discussed.     

Synthesis and pharmacological activity of silyl isoxazolines 2

Silyl isoxazolines have been synthesized by [2+3] cycloaddition reaction of nitrile oxides to vinyl- and allylsilanes. The addition of 3-pyridylnitrile oxide to 1,3-divinyl-1,1,3,3-tetraphenyldisiloxane affords 1,3-bis{5-[3-(3-pyridyl)isoxazolin-2-yl]}-1,1,3,3-tetraphenyldisiloxane; the latter exists as a mixture of trans- and cis-isomers.The bond angle of the Si–O–Si fragment in thetrans-isomer equals 180(3)° and in the cis-isomer it is 162(3)°.The pharmacological properties of 4-[3-(5-trimethylsilylisoxazolin-2-yl)]pyridinium-chloride have been studied.     

Cross-conjugated biradicals: Kinetics and kinetic isotope effects in the thermal isomerizations of cis- and trans-2,3-dimethylemethylnecyclopropane,cis- and trans-3,4-dimethyl-1,2-dimethylenecyclobutane,and of 1,2,8,9-decatetraene

cis- and trans - 2,3 - Dimethylenemethylenecyclopropane ($\text{C}$ and $\text{T}$) interconvert at 160.0° with a small normal kinetic isotope effect (KIE) when the exo-methylene is deuterated, but the 1,3-shift products, 2-methylethylidenecyclopropane, show a large normal KIE, 1.35 and 1.31, when formed from $\text{C}$ and $\text{T}$, respectively. This data can be interpreted in terms of either parallel reactions or a common trimethylenemethane diradical intermediate formed with a normal KIE of 1.11 and closing to 1,3-shift product with a normal KIE of 1.29 due to the effect of deuterium in the required 90° rotation of the exo-methylene carbon.The kinetics of the thermal 1,3- and 3,3-shifts of cis- and rans-3,4-dimethyl-1,2-dimethylenecyclobutane ($\text{CB}$ and $\text{TB}$) were determined in a flow reactor. The first order rate constants are log k_CB (sec^?1) = 13.7 ? 42,200/2.3 RT and log k_TB (sec^?1) = 13.6 ? 41,900/2.3 RT (E_a in kcal/m) which compare favorably to that from the parent hydrocarbon. 1,2-dimethylenecyclobutane, after reasonable correction for dimethyl substitution.Rearrangement of $\text{TB}$ and its bis(dideuteriomethylene) derivative at 230.0° revealed a normal KIE of 1.08. This KIE could be interpreted in terms of either a methylene rotational isotope effect in a concerted reaction or formation of a bisallyl diradical with the expected normal rotational IE on closure to the 1,3-shift product of 1.12 with no IE in the ring opening when the result is corrected for return of the biradical to starting material.The kinetics of intramolecular 2 + 2 cycloaddition of 1,2,8,9-decatetraene were determined in a flow reactor. The first order rate constant is log k(sec^?1) = 9.4 ? 30,800/2.3 RT (E_a in kcal/m). These energetics are compared with those of other 2 + 2 cycloadditions. The major product is 3,4-dimethylenecyclooctene ($\text{DC}$) which is also found from the minor product, cis-7,8-dimethylenebicvyclo[4.2.0]octane ($\text{CO}$), at higher temperatures. The trans isomer, $\text{TO}$, also gives $\text{DC}$ at about the same rate as $\text{CO}$.     

Methyl 1,3-Diphenylbicyclo[1.1.0]butane-2-exo-carboxylate. new example of the thermal inversion of bicyclobutane system

A fact of a reversible thermal inversion of exo- and endo-isomers of methyl 1,3-diphenylbicyclo[1.1.0] butane-2-carboxylate was established experimentally. The equilibrium constant of the process at 126°C is 14.2 with endo-isomer prevailing. Using DFT/PBE/L22 method the geometry of the isomers was optimized and also the geometry of the previously studied related exo,exo- and endo,endo-isomers of dimethyl 1,3-diphenylbicyclo[1.1.0] butane-2,4-dicarboxylate. The energy barrier of these mutual conversions was estimated.     

Kinetics of the reactions of O3 and OH radicals with a series of dialkenes and trialkenes at 294 ± 2 K

Rate constants for the gas phase reactions of O₃ and OH radicals with 1,3-cycloheptadiene, 1,3,5-cycloheptatriene, and cis- and trans-1,3,5-hexatriene and also of O₃ with cis-2,trans-4-hexadiene and trans -2,trans -4-hexadiene have been determined at 294 ± 2 K. The rate constants determined for reaction with O₃ were (in cm³ molecule^-1s^?1 units): 1,3-cycloheptadiene, (1.56 ± 0.21) × 10^-16; 1,3,5-cycloheptatriene, (5.39 ± 0.78) × 10^?17; 1,3,5-hexatriene, (2.62 ± 0.34) × 10^?17; cis?2,trans-4-hexadiene, (3.14 ± 0.34) × 10^?16; and trans ?2, trans -4-hexadiene, (3.74 ± 0.61) × 10^?16; with the cis- and trans-1,3,5-hexatriene isomers reacting with essentially identical rate constants. The rate constants determined for reaction with OH radicals were (in cm³ molecule^?1 s^?1 units): 1,3-cycloheptadiene, (1.31 ± 0.04) × 10^?10; 1,3,5-cycloheptatriene, (9.12 × 0.23) × 10^?11; cis-1,3,5-hexatriene, (1.04 ± 0.07) × 10^?10; and trans 1,3,5-hexatriene, (1.04 ± 0.17) × 10^?10. These data, which are the first reported values for these di- and tri-alkenes, are discussed in the context of previously determined O₃ and OH radical rate constants for alkenes and cycloalkenes.     

Stereochemical studies-XXXIII. Saturated heterocycles-IX: Synthesis and conformations of stereoisomeric cis- and troans-tetramethylene- and pentamethylenedihydro-1,3-oxazines

By the reaction of cis- and trans-2-aminomethylcyclohexanol (1, 2), cis- and trans-2-hydroxymethyl-cyclohexylamine (3,4) and the homologous cycloheptane derivatives (5-8) with ethyl p-chlorobenzimidate (11), cis- and trans-5,6-tetramethylene- and pentamethylene-2,3,5,6-tetrahydro-4H-1,3-oxazines (12,13,16,17) and cis- and trans-4,5-tetramethylene- and pentaimethylene-4,5-dihydro-6H-1,3-oxazines (14, 15, 18, 19) were prepared. The amidine intermediate of the ring-closure reaction was isolated, and the mechanism of the acid-catalysed reaction is discussed. It follows from the ¹H NMR data that in the preferred conformations of the cis-tetramethylene-tetrahydrooxazines the methylene group of the hetero ring is equatorial and the hetero atom (O or N) axial. In contrast, the conformation equilibria of the cis pentamethylene derivatives, in accordance with earlier X-ray analysis, are shifted towards the conformer containing the methylene group in isoclinal and the hetero atom in equatorial position. The preferred conformations 12a and 14a of the tetramethylene derivatives 12 and 14 were also determined by X-ray crystal analysis.     

Reactions of dispiro[2.0.2.2]oct-7-ene. Electrophilic and free radical additions

Dispiro[2.0.2.2]oct-7-ene 1 was synthesized by debrominatioa of cis- and trans-7,8-dibromodispiro[2.0.2.2]octane 3a with LAH and by dechlorination of cis- and trans-7,8-dichlorodispiro[2.0.2.2]octane 3b with magnesium. Stepwise electrophilic additions to 1 of HBr, HI, Br₂ and Cl₂ were studied. The major products (and yields) from these reactions were: 7-bromodispiro[2.0.2.2]octane 2a (43%), 4-iodo-4,5-ethanospiro[2,3]hexane 4b (ca. 50%); trans-3a (40%); and cis-3b (20%). Free-radical addition of hydrogen bromide to 1 gave an 80% yield of 7-bromodispiro[2.0.2.2]octane 2a. At ?10°, hydroboration-oxidation of 1 was found to give mainly 7-hydroxydispiro[2.0.2.2]octane 2a in ca. 90% yield; at 25°, near equal amounts of 2c and 4-(2-hydroxyethyl) spiro[2.3]hex-4-ene 14 were obtained.     

δ-lactones from grignard reactions : Their isolation and structure characterization

Grignard reactions on methyl 4-methyl, 5-oxo, 5-phenyl (pX substituted) pentanoates 1-6 (X = H, Me, F, Cl, Br, OMe) produced mixtures of cis-(7-11) and trans-(12-16) tetrahydro 5,6 dimethyl-6-phenyl -2H-pyran-2-ones. They were isolated by HPLC and characterized by ¹H and ¹³C techniques. The stereochemistry of Grignard reactions in THF with CH₃MgCl was determined at 0° and 60°.