Thermal reactions of anti- and syn-dispiro[5.0.5.2]tetradeca-1,8-dienes: stereomutation and fragmentation to 3-methylcyclohexenes. Entropy-dictated product ratios from diradical intermediates?

A series of cyclobutanes substituted 1,2- by polyenes of increasing radical-stabilizing power has been investigated to test the proposition that stabilization energies obtained independently from apposite, cis,trans geometric isomerizations can be successfully transferred to another system, in this paper, cyclobutanes. The first member of the series, 3-methylenecyclohexene (1), is photodimerized to anti- and syn-dispiro[5.0.5.2]tetradeca-1,8-dienes (anti-2 and syn-2), which undergo stereomutation (stereochemical interconversion) and cycloreversion (fragmentation) to 1 when heated in the range 72.1-118.2 degrees C: anti-2 --> syn-2, DeltaH() = 30.3 kcal mol(-)(1), DeltaS() = 0.2 cal mol(-)(1) K(-)(1); anti-2 --> 1, DeltaH() = 32.8 kcal mol(-)(1), DeltaS() = +8.0 cal mol(-)(1) K(-)(1). Agreement with an enthalpy of activation predicted by assuming full allylic stabilization in a hypothetical diradical intermediate is good. An example of further activation by a radical-stabilizing group is manifested by the approximately 20 000-fold acceleration in rate shown by the system 1-phenyl-3-methylenecyclohexene (3) and anti- and syn-2,9-diphenyldispiro[5.0.5.2]tetradeca-1,8-dienes (anti-4 and syn-4), measured, however, only at 43.6 degrees C. In both systems 2 and 4, volumes of activation for stereochemical interconversion and cycloreversion have been determined and found to be essentially identical within experimental uncertainties, DeltaV() = +10.2 +/- 1.0 and +12.6 +/- 1.4 cm(3) mol(-)(1), respectively (weighted means). These strongly positive values are consistent with the rate-determining step being the first bond-breaking, while the near identity of the volumes of activation argues against the indispensable second bond-breaking being a determining factor in fragmentation. These results are consistent with the theoretically based construct of Charles Doubleday for the paradigm, cyclobutane, in which the ratio between two channels of exit from a "generalized common biradical" is not controlled by enthalpy and entropy, as in the transition state model, but by entropy alone.     

Inherently chiral molecular clips: synthesis, chiroptical properties, and application to chiral discrimination

Inherently chiral molecular clips (MCs), pseudoenantiomeric anti-1 and anti-2, as well as mesoid syn-3, were synthesized by diastereodifferentiating repetitive Diels-Alder reactions of the achiral bisdienophile 6 with chiral diene 5 generated in situ from (-)-menthyl 3,4-bis(dibromomethyl)benzoate 4. These MCs were successfully separated by chiral HPLC to give optically active anti-1 and anti-2 and almost optically inactive syn-3. The structures of anti-1, anti-2, and syn-3 were assigned by high-resolution NMR and the absolute configurations of anti-1 and anti-2 were determined by the exciton-chirality method. Optically active anti-2 can serve as a chiral host. It binds the HCl adduct of D-tryptophan methyl ester (D-TrpOMeHCl) 3.5 times stronger than the L-enantiomer (KD/KL=3.5).     

Crucial dependence of chemiluminescence efficiency on the syn/anti conformation for intramolecular charge-transfer-induced decomposition of bicyclic dioxetanes bearing an oxidoaryl group

Thermally stable rotamers of bicyclic dioxetanes bearing 6-hydroxynaphthalen-1-yl (anti-5a and syn-5a), 3-hydroxynaphthalen-1-yl (anti-5b and syn-5b), and 5-hydroxy-2-methylphenyl groups (anti-5c and syn-5c) were synthesized. These dioxetanes underwent TBAF (tetrabutylammonium fluoride)-induced decomposition accompanied by the emission of light in DMSO and in acetonitrile at 25 °C. For all three pairs of rotamers, the chemiluminescence efficiency Φ(CL) for anti-5 was 8-19 times higher than that for syn-5, and the rate of CTID (charge-transfer-induced decomposition) for anti-5 was faster than that for syn-5. The chemiluminescence spectra of the rotamers for 5a and 5c, respectively, were different. This discrepancy in the chemiluminescence spectra between rotamers can presumably be attributed to the difference in the structures of de novo keto imide anti-14 and syn-14 in an excited state, which inherit the structures of the corresponding intermediary anionic dioxetanes anti-13 and syn-13. The important difference in chemiluminescence efficiency between anti-5 and syn-5 is discussed from the viewpoint of a chemiexcitation mechanism for CTID of oxidophenyl-substituted dioxetane.     

Quasi-octahedral complexes of pentamethylcyclopentadienyliridium(III) bearing bis(diphenylphosphinomethyl)phenylphosphine (dpmp)

Reaction of [Cp*IrCl2]2 (1) with dpmp in the presence of KPF6 afforded a binuclear complex [Cp*IrCl(dpmp-P1,P2;P3)IrCl2Cp*](PF6) (2) (dpmp =(Ph2PCH2)2PPh). The mononuclear complex [Cp*IrCl(dpmp-P1,P2)](PF6) (4) was generated by the reaction of [Cp*IrCl2(BDMPP)](BDMPP =PPh[2,6-(MeO)2C6H3]2) with dpmp in the presence of KPF6. These mono- and binuclear complexes have four-membered ring structures with a terminal and a central P atom of the dpmp ligand coordinated to an iridium atom as a bidentate ligand. Since there are two chiral centers at the Ir atom and a central P2 atom, there are two diastereomers that were characterized by spectrometry. Complexes anti-4 and syn-4 reacted with [Cp*RhCl2]2 or [(C6Me6)RuCl2]2, giving the corresponding mixed-metal complexes, anti- and syn- [Cp*IrCl(dppm-P1,P2;P3)MCl2L](PF6) (6: M = Rh, L = Cp*; 7: M = Ru, L = C6Me6). Treatment with AuCl(SC4H8) gave tetranuclear complexes, anti- and syn-8 [[Cp*IrCl(dppm-P1,P2;P3)AuCl]2](PF6)2 bearing an Au-Au bond. Reaction of anti- with PtCl2(cod) generated the trinuclear complex anti-9, anti-[[Cp*IrCl(dppm-P1,P2;P3)]2PtCl2](PF6)2. These reactions proceeded stereospecifically. The P,O-chelated complex syn-[Cp*IrCl(BDMPP-P,O)] (syn-10)(BDMPP-P,O = PPh[2,6-(MeO)2C6H3][2-O-6-(MeO)C6H3]2) reacted with dpmp in the presence of KPF6, generating the corresponding anti-complex as a main product as well as a small amount of syn-complex, [Cp*Ir(BDMPP-P,O)(dppm-P1)](PF6) (11). The reaction proceeded preferentially with inversion. The reaction processes were investigated by PM3 calculation. anti- was treated with MCl2(cod), giving anti-[Cp*Ir(BDMPP-P,O)(dppm-P1;P2,P3)MCl2](PF6)(14: M = Pt; 15: M = Pd), in which the MCl2 moiety coordinated to the two free P atoms of anti-11. The X-ray analyses of syn-2, anti-2, anti-4, anti-8 and anti-11 were performed.     

Asymmetric synthesis of 3,4-anti- and 3,4-syn-substituted aminopyrrolidines via lithium amide conjugate addition

The diastereoselective conjugate addition of homochiral lithium amides to methyl 4-(N-allyl-N-benzylamino)but-2-enoate has been used as the key step in a simple and efficient protocol for the preparation of 3,4-substituted aminopyrrolidines. This protocol provides a complementary and stereoselective route to both anti- and syn-3-amino-4-alkylpyrrolidines as well as anti- and syn-3-hydroxy-4-aminopyrrolidines, in high de and ee viabeta-amino enolate functionalisation. This methodology has been applied to the synthesis of anti-(3S,4S)- and syn-(3R,4S)-3-methoxy-4-(N-methylamino)pyrrolidine.     

A Catalytic Asymmetric Synthesis ofN-Boc-beta-Methylphenylalanines

An efficient, stereodivergent, and enantioselective synthesis of the syn and anti diastereomers of N-Boc-beta-methylphenylalanine has been developed. Starting from enantiomerically pure (2S,3S)-2,3-epoxy-3-phenyl-1-propanol, a three-step sequence, consisting of the oxidation of the primary alcohol up to the carboxyl stage, ring opening of the epoxy acid with Me(2)CuCNLi(2), and esterification of the resulting hydroxy acid with methyl iodide, leads to the hydroxy ester anti-10, which has been converted in a stereodivergent manner into both the (2S,3R) and the (2R,3R) diastereomers of N-Boc-beta-methylphenylalanine, syn-1 and anti-1, respectively. Activation of the secondary hydroxy group in anti-10 as a mesylate, followed by nucleophilic displacement with sodium azide, hydrogenolysis with simultaneous protection of the amino group, and saponification with LiOH, affords syn-1. The same reaction sequence applied to syn-10, obtained in turn by Mitsunobu reaction of anti-10 with p-nitrobenzoic acid followed by the hydrolysis of the resulting p-nitrobenzoate, leads to anti-1. Both products have been obtained with >/=99% enantiomeric excess.     

Antimony(III) Halide-Assisted Stereospecific Coordination of Thione

The antimony halide-aided stereospecific coordination of a cyclic thiourea-type of ligand is observed for the first time. The antimony(III) imidazole thione complexes syn-[( L¹ )SbCl₃] ( syn- 1 ) and anti-[( L¹ )SbBr₃] ( anti- 2 ) have been synthesized in very good yield by the reaction between the spatially defined steric impact ligand [(IPaul)S] ( L¹ ) ([(IPaul)S]=1,3-bis(2,4-methyl-6-diphenyl phenyl)imidazole thione) and corresponding antimony halide. The stereoselective formation of complexes syn- 1 and anti- 2 has been confirmed by both NMR and single-crystal X-ray diffraction studies. Interestingly the stereospecific nature of syn- 1 and anti- 2 remains intact in solution. Furthermore, the thermal stability of antimony(III) imidazole thione complexes were examined by TGA analysis.     

Stereospecificity of the dehydratase domain of the erythromycin polyketide synthase

The dehydratase (DH) domain of module 4 of the 6-deoxyerythronolide B synthase (DEBS) has been shown to catalyze an exclusive syn elimination/syn addition of water. Incubation of recombinant DH4 with chemoenzymatically prepared anti-(2R,3R)-2-methyl-3-hydroxypentanoyl-ACP (2a-ACP) gave the dehydration product 3-ACP. Similarly, incubation of DH4 with synthetic 3-ACP resulted in the reverse enzyme-catalyzed hydration reaction, giving an ～3:1 equilbrium mixture of 2a-ACP and 3-ACP. Incubation of a mixture of propionyl-SNAC (4), methylmalonyl-CoA, and NADPH with the DEBS β-ketoacyl synthase-acyl transferase [KS6][AT6] didomain, DEBS ACP6, and the ketoreductase domain from tylactone synthase module 1 (TYLS KR1) generated in situ anti-2a-ACP that underwent DH4-catalyzed syn dehydration to give 3-ACP. DH4 did not dehydrate syn-(2S,3R)-2b-ACP, syn-(2R,3S)-2c-ACP, or anti-(2S,3S)-2d-ACP generated in situ by DEBS KR1, DEBS KR6, or the rifamycin synthase KR7 (RIFS KR7), respectively. Similarly, incubation of a mixture of (2S,3R)-2-methyl-3-hydroxypentanoyl-N-acetylcysteamine thioester (2b-SNAC), methylmalonyl-CoA, and NADPH with DEBS [KS6][AT6], DEBS ACP6, and TYLS KR1 gave anti-(2R,3R)-6-ACP that underwent syn dehydration catalyzed by DEBS DH4 to give (4R,5R)-(E)-2,4-dimethyl-5-hydroxy-hept-2-enoyl-ACP (7-ACP). The structure and stereochemistry of 7 were established by GC-MS and LC-MS comparison of the derived methyl ester 7-Me to a synthetic sample of 7-Me.     

Stereoselective sulfur extrusion reaction of syn- and anti-10,20-dibromo-2,3,12,13-tetrathia[4.4]metacyclophanes to the corresponding syn- and anti-dithia[3.3]metacyclophanes

A new cyclophane, 10,20-dibromo-2,3,12,13-tetrathia[4.4]metacyclophane (1) , has been synthesized by the oxidative coupling reaction of 2,6-bis(mercaptomethyl)-1-bromobenzene with I₂. Both syn and anti isomers of 1 can be isolated at room temperature. The thermal sulfur extrusion reaction of anti- 1 with (Et₂N)₃P afforded anti-9,18-dibromo-2,11-dithia[3.3]metacyclophane, while syn- 1 gave 9,19-dibromo-2,11,12-trithia[3.4]metacyclophane. syn-9,18-Dibromo-2,11-dithia[3.3]metacyclophane was produced from the photochemical sulfur extrusion of syn- 1 with (MeO)₃P.     

Nucleophilic addition to 2,3-disubstituted butanal derivatives and their application to natural product synthesis

The reaction of 2,3-anti-2-tert-butyldimethylsiloxy-3-substituted butanal derivative [anti-B, (±)-10 and (±)-16] derived from trans-(2,3)-epoxy butanoate (1) with carbon nucleophiles [α-furyl anion, acetate anion, and indium (In)-assisted allyl anion] has been investigated to give selectively the anti-, anti-adduct D. This anti-stereoselection could be explained by the Felkin-Anh transition state model. Thus obtained anti-, anti-adducts (±)-17 and (±)-38 were formally converted to natural products, (±)-asperlin (2) and (±)-olivose (4), respectively. The major anti-, anti-adduct (±)-26 was converted to (±)-digitoxose (3), while the minor anti-, syn-adduct (±)-27 was also converted to (±)-olivose (4). The reaction of (±)-10 with tert-butyl acetate anion gave predominantly afforded the anti-, anti-adduct (±)-23, which was converted to (±)-1,5-dideoxyhexitol (25). Alternately, the reaction of 2,3-syn-2-tert-butyldimethylsiloxy-3-p-methoxyphenoxy butanal derivative [syn-B, (±)-14] derived from trans-(2,3)-epoxy butanoate (1) with carbon nucleophile (In-assisted allyl anion) afforded a ca. 1 : 1 mixture of the syn-, anti-adduct E [(±)-32 or (±)-34] and syn-, syn-adduct F [(±)-33 or (±)-35]. After separation of this mixture, (±)-34 and (±)-35 were separately converted to (±)-oliose (5) and (±)-boivinose (6), respectively.     

Stereocontrolled route to vicinal diamines by [3.3] sigmatropic rearrangement of allyl cyanate: asymmetric synthesis of anti-(2R,3R)- and syn-(2R,3S)-2,3-diaminobutanoic acids

A stereocontrolled route via allyl 1,2-diols to vicinal diamines based on the [3.3] sigmatropic rearrangement of allyl cyanate has been developed. Our approach consists of two consecutive steps: stereoselective construction of allyl anti- and syn-1,2-diols followed by [1,3]-chirality transfer by sigmatropic rearrangement, which allow an access to anti-(2R,3R)- and syn-(2R,3S)-2,3-diaminobutanoic acids. [reaction: see text]     

Synthesis, conformational stability, and asymmetric transformation of atropisomeric 1,8-bisphenolnaphthalenes

Highly congested, axially chiral 1,8-bisphenolnaphthalenes have been synthesized in 75% overall yield by palladium-catalyzed Suzuki coupling of 1,8-diiodonaphthalene and 4-methoxy-2-methylphenylboronic acid followed by regioselective formylation and deprotection. The C(2)-symmetric anti-stereoisomers of 1,8-bis(2'-methyl-4'-hydroxy-5'-formylphenyl)naphthalene, 5, and its diimine analogues 9 and 10 were found to be significantly more stable than the corresponding syn-isomer. Crystallographic analysis revealed that this stereochemical preference results from a unique intramolecular hydrogen bonding motif and concomitant minimization of steric repulsion. Triaryl 5 proved stable to rotation about the chiral axes at room temperature and the enantiomers were isolated via formation of diastereomeric diimines with (R)-2-amino-1-propanol and (R)-2-amino-3-methyl-1-butanol, respectively, chromatographic separation, and mild hydrolysis. Slow syn/anti-interconversion of 5, 9, and 10 was observed at enhanced temperatures and the diastereomerization and enantiomerization processes were monitored by CD and NMR spectroscopy. The Gibbs activation energy, ΔG(?), for the isomerization of 5 was determined as 103.7 (102.4) kJ/mol for the conversion of the anti-(syn-) to the syn-(anti-)isomer at 45.0 °C. Condensation of 5 with two chiral amino alcohols generates diimines that undergo quantitative asymmetric transformation of the first kind toward the thermodynamically favored (P,P,R,R)- or (M,M,S,S)-atropisomer, respectively. The incorporation of two imino alcohol units controls the outcome of this unidirectional atropisomerization, i.e. the central chirality of the amino alcohol used induces a rigid, axially chiral triaryl scaffold with perfect stereocontrol. Accordingly, the rotational energy barrier for the conversion of (M,M,S,S)-9 to its syn-isomer is significantly increased and was determined as 115.7 kJ/mol at 58.0 °C.     

Facile η5-η3 hapticity interconversion in pentamethylcyclopentadienyl ruthenium(II) complexes containing a phenylmethallyl ("open indenyl") ligand

The indenyl effect has been introduced to pentadienyl ("open cyclopentadienyl") chemistry by preparation of the phenylmethallyl ("open indenyl") ligand oInd(Me). The reaction of its potassium salt K(oInd(Me)) with [(η(5)-C(5)Me(5))RuCl](4) afforded the sandwich complex [(η(5)-C(5)Me(5))Ru(η(5)-oInd(Me))] (1), which, upon treatment with PMe(3), CO, and 2,6-dimethylphenyl isocyanide (CN-o-Xy), easily underwent η(5)-η(3) hapticity interconversion and formed the complexes [(η(5)-C(5)Me(5))Ru(η(3)-oInd(Me))(L)] (2, L = PMe(3); 3, L = CO; 4, L = CN-o-Xy). In these complexes, the η(3)-bound phenylmethallyl ligand adopts an anti-conformation with regard to the relative positions of the phenyl and methyl substituents. For the PMe(3) complex anti-2, slow conversion to the syn-isomer was observed, and this equilibrium reaction was monitored by NMR spectroscopy at 50 °C to determine a first order rate constant of k(323 K) = 6.57 × 10(-6) (± 0.02 × 10(-6)) s(-1) and an activation barrier of ΔG° = 26.8 kcal mol(-1). DFT calculations afforded a stabilization of syn-2 and syn-3 by ΔG(298) = -1.54 and -1.74 kcal mol(-1) over the respective anti-isomer.     

Asymmetric synthesis of anti- and syn-2,3-diamino esters using sulfinimines. Water and concentration effects

[reaction: see text] In the absence of water, an excess of the lithium enolate of N-(diphenylmethylene)glycine ethyl ester (4) adds to sulfinimines to give syn-2,3-diamino esters 6, and in the presence of water, this enolate gives the anti-2,3-diamino esters 5. These unusual results are interpreted in terms of those factors that inhibit the retro-Mannich fragmentation in the diamino esters.     

Concerning the 1,5-stereocontrol in tin(iv) chloride promoted reactions of 4- and 5-alkoxyalk-2-enylstannanes: trapping intermediate allyltin trichlorides using phenyllithium

Transmetallation of the 5-benzyloxy-4-methylpent-2-en-1-yl(tributyl)- and -(triphenyl)stannanes 1 and 8 using tin(iv) chloride generates an allyltin trichloride that reacts with aldehydes to give (Z)-1,5-anti-6-benzyloxy-5-methylhex-3-en-1-ols 2. The allyltin trichloride believed to be the key intermediate in these reactions has been trapped by phenyllithium to give anti-5-benzyloxy-4-methylpent-1-en-3-yl(triphenyl)stannane 9. Transmetallation of this anti-5-benzyloxy-4-methylpent-1-en-3-yl(triphenyl)stannane 9 generated an allyltin trichloride that reacted with aldehydes to give the (Z)-1,5-syn-6-benzyloxy-5-methylhex-3-en-1-ols 23 and was trapped by phenyllithium to give syn-5-benzyloxy-4-methylpent-1-en-3-yl(triphenyl)stannane 24. Similar stereoselectivity was observed for tin(iv) chloride promoted reactions of this syn-5-benzyloxy-4-methylpent-1-en-3-yl(triphenyl)stannane 24 with aldehydes and with phenyllithium. The allyltin trichlorides generated by transmetallation of 4-hydroxy- and 4-benzyloxy-pent-2-enyl(triphenyl)stannanes 34 and 35 were similarly trapped by phenyllithium to give 4-hydroxy- and 4-benzyloxy-pent-1-en-3-ylstannanes 36 and 37 whose configurations were established by correlation with known compounds. This work confirmed the configurations of the intermediate allyltin trichlorides involved in tin(iv) chloride promoted reactions of 4- and 5-alkoxypent-2-enylstannanes with aldehydes and showed that the high levels of remote stereocontrol were due mainly to kinetically controlled transmetallation. A fuller mechanistic scheme is proposed for the reactions in the 5-benzyloxy-4-methylpent-2-enylstannane series together with relevant (119)Sn NMR data.     

Products from enzyme-catalyzed oxidations of norcarenes

Recent studies revealed that norcarane (bicyclo[4.1.0]heptane) is oxidized to 2-norcarene (bicyclo[4.1.0]-hept-2-ene) and 3-norcarene (bicyclo[4.1.0]hept-3-ene) by iron-containing enzymes and that secondary oxidation products from the norcarenes complicate mechanistic probe studies employing norcarane as the substrate (Newcomb, M.; Chandrasena, R. E. P.; Lansakara-P., D. S. P.; Kim, H.-Y.; Lippard, S. J.; Beauvais, L. G.; Murray, L. J.; Izzo, V.; Hollenberg, P. F.; Coon, M. J. J. Org. Chem. 2007, 72, 1121-1127). In the present work, the product profiles from the oxidations of 2-norcarene and 3-norcarene by several enzymes were determined. Most of the products were identified by GC and GC-mass spectral comparison to authentic samples produced independently; in some cases, stereochemical assignments were made or confirmed by 2D NMR analysis of the products. The enzymes studied in this work were four cytochrome P450 enzymes, CYP2B1, CYPDelta2E1, CYPDelta2E1 T303A, and CYPDelta2B4, and three diiron-containing enzymes, soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath), toluene monooxygenase (ToMO) from Pseudomonas stutzeri OX1, and phenol hydroxylase (PH) from Pseudomonas stutzeri OX1. The oxidation products from the norcarenes identified in this work are 2-norcaranone, 3-norcaranone, syn- and anti-2-norcarene oxide, syn- and anti-3-norcarene oxide, syn- and anti-4-hydroxy-2-norcarene, syn- and anti-2-hydroxy-3-norcarene, 2-oxo-3-norcarene, 4-oxo-2-norcarene, and cyclohepta-3,5-dienol. Two additional, unidentified oxidation products were observed in low yields in the oxidations. In matched oxidations, 3-norcarene was a better substrate than 2-norcarene in terms of turnover by factors of 1.5-15 for the enzymes studied here. The oxidation products found in enzyme-catalyzed oxidations of the norcarenes are useful for understanding the complex product mixtures obtained in norcarane oxidations.     

Influence of carrier ligand NH hydrogen bonding to the O6 and phosphate group of guanine nucleotides in platinum complexes with a single guanine ligand

Coordinated N,N',N"-trimethyldiethylenetriamine (Me3dien) has several possible configurations: two have mirror symmetry (R,S configurations at the terminal nitrogens) and the terminal N-Me's anti or syn with respect to the central N-Me (anti-(R,S) and syn-(R,S) isomers, respectively), and two are nonsymmetrical (R,R and S,S configurations at terminal nitrogens, rac denotes a 1:1 mixture of the two isomers). For each configuration, two Me3dienPtG atropisomers can be formed (anti or syn orientation of central N-Me and G 06, G = guanine derivative), and these can be observed since the terminal N-Me's decrease the rate of G rotation about the Pt-N7 bond. In symmetrical syn-(R,S)-Me3dienPtG derivatives with G = 9-EtG and 3'-GMP, the anti rotamer, which can form O6-NH H-bonds, was slightly favored over the syn rotamer but never more than 2:1. This anti rotamer is also favored by lower steric repulsion between the terminal N-Me's and G O6; thus, the contribution of O6-NH H-bonding to the stability of the anti rotamer could be rather small. With G = 5'-GMP, an O6-NH H-bond in the anti rotamer and a phosphate-NH H-bond in the syn rotamer can form. Only the syn rotamer was detected in solution, indicating that NH H-bonds to 5'-phosphate are far more important than to O6, particularly since steric factors favor the anti rotamer. Interconversion between rotamers was faster for syn-(R,S)- than for rac-Me3dien derivatives. This appears to be determined by a smaller steric impediment to G rotation of two "quasi equatorial" N-Me's, both on one side of the platinum coordination plane (syn-(R,S) isomer), than one "quasi equatorial" and one "quasi axial" N-Me on either side of the coordination plane (rac isomer).     

Diastereoselectivity in the McLafferty rearrangement of photoionized 3-methyl valeramide

The McLafferty rearrangement of photoionized 3-methyl valeramide proceeds quasi-barrierless and with high regioselectivity. The mass spectra of the stereospecifically labeled syn- and anti-[4-D(1)]-diastereomers reveal a strong preference for activation of the gamma-hydrogen/deuterium in anti-position relative to the methyl group at C(3), which serves as a steric marker. Quantitative analysis of the fragmentation patterns of other photoionized isotopomers permits the determination of primary and secondary kinetic isotope effects (KIEs), the branching ratios of competing McLafferty reactions, and the steric effect (SE) associated with transfer of the diastereotopic H(D) atoms at C(4). While the associated KIEs of the title reaction are negligible, the steric effect (SE = 2.9) is remarkably large for the otherwise flexible, monofunctional compound. The findings can be explained by a preferentially chairlike transition structure for the initial gamma-H atom transfer.     

Development and application of a new general method for the asymmetric synthesis of syn- and anti-1,3-amino alcohols

A general method is described for asymmetric synthesis of both syn- and anti-1,3-amino alcohols. The first application of metalloenamines derived from N-sulfinyl imines is reported for the highly diastereoselective addition to aldehydes. The reduction of the product beta-hydroxy N-sulfinyl imines 2 with catecholborane and LiBHEt(3) provides syn- and anti-1,3-amino alcohols with very high diastereomeric ratios. This method was found to be effective for a variety of substrates incorporating either aromatic or various aliphatic substituents. The convergent and efficient asymmetric syntheses of the two natural products, (-)-8-epihalosaline and (-)-halosaline, were also accomplished.     

Regio- and stereochemically controlled formation of hydroxamic acid containing anti- or syn-1,4-cycloalkenols from acylnitroso-derived Diels-Alder adducts

Treatment of acylnitroso hetero Diels-Alder cycloadducts 2 with iron(III) or copper(II) in an alcohol solvent induces ring opening to afford predominantly monocyclic anti-1,4-hydroxamic acids 3. However, treatment of cycloadducts 2 with copper(II) in toluene reverses the stereoselectivity of the ring opening to afford syn-1,4-hydroxamic acids 4. These regio- and stereoselective processes separately provide anti-1,4- and syn-1,4-disubstituted cyclopentenes while regenerating a hydroxamic acid moiety, thus enhancing the chemical versatility of the Diels-Alder cycloadducts.