- A One-Pot Iodo-Cyclization/Transition Metal-Catalyzed Cross-Coupling Sequence: Synthesis of Substituted Oxazolidin-2-ones from N-Boc-allylamines
-
A one-pot iodo-cyclization/transition metal-catalyzed cross-coupling sequence is reported to access various C5-functionalized oxazolidin-2-ones from unsaturated N-Boc-allylamines. Depending on the Grignard reagents used for the cross-coupling, e.g., aryl- or cyclopropylmagnesium bromide, a cobalt or copper catalyst has to be used to obtain the functionalized oxazolidin-2-ones in good yields.
- Chaumont-Olive, Pauline,Cossy, Janine
-
-
- A fit for purpose synthesis of Bruton's tyrosine kinase inhibitor GDC-0852
-
The development of an expedient synthesis to GDC-0852 (1), a reversible BTK inhibitor drug candidate, is described. The key starting material tricyclic lactam 5 was prepared by an annulation reaction of unprotected piperidine-2-carbaldehyde HCl salt (20) and N-Boc piperidine-2,4-dione 21 in a safe and scalable manner. A highly selective Pd-catalyzed C[sbnd]N coupling of lactam 5 and linker 2a, followed by Suzuki?Miyaura coupling to fragment 8 subsequently provided a direct and convergent access to the penultimate 17. A simple NaBH4 aldehyde reduction completed the synthesis to GDC-0852 (1) in high yield (54% over 3 steps from 5) and purity (99.0 A% HPLC).
- Lim, Ngiap-Kie,Zhang, Haiming,Sowell, C. Gregory,Gosselin, Francis
-
-
- SUBSTITUTED AMINO TRIAZOLES USEFUL AS HUMAN CHITINASE INHIBITORS
-
Disclosed are amino triazole compounds substituted with a piperidinyl ring that is itself substituted with a heterocyclic ring. These compounds are inhibitors of acidic mammalian chitinase and chitotriosidase. Also disclosed are methods of using the compounds to treat asthma reactions caused by allergens, as well as acute and chronic inflammatory diseases, autoimmune diseases, dental diseases, neurologic diseases, metabolic diseases, liver diseases, polycystic ovary syndrome, endometriosis, and cancer.
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-
-
- PROCESS FOR MAKING TRICYCLIC LACTAM COMPOUNDS
-
Processes are described for the preparation of tricyclic lactam compound of Formula (I), having the structure and intermediates useful for the preparation of (I).
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- Benzimidazole-2-piperazine compound, its pharmaceutical composition and its preparation and use
-
The invention relates to a benzimidazole-2-piperazine derivative and a preparing method and application of the benzimidazole-2-piperazine derivative in medicine, in particular to a novel benzimidazole-2-piperazine derivative shown in the general formula (I), a preparing method of the derivative, a pharmaceutical composition containing the derivative and application of the derivative serving as a therapeutic agent, especially serving as a poly (ADP-ribose) polymerase (PARP) inhibitor. In the general formula (I), R refers to hydrogen or halogen, G refers to carbonyl or methylene, m is 1-2, n is 1-3, and Q refers to hydrogen or C1-C4 alkyl. When X is methylene and Y is NR1 or methylene, X is NR1; R1 refers to hydrogen, C1-C6 alkyl, benzyl, COR2 or SO2R2; R2 refers to the following groups which are not substituted or groups substituted by 1-3 substituent groups, including C1-C6 alkyl, C3-C8 naphthenic base, phenyl, benzyl, naphthyl and C5-C10 aromatic heterocycle base, heterocycle in the C5-C10 aromatic heterocycle base comprises 1-3 heteroatoms selected from N, O and S, and the substituent groups are selected from the following atoms or groups of C1-C6 alkyl, C1-C6 alkoxy, halogen, amidogen, nitryl, sulfydryl, hydroxyl, cyanogroup and trifluoromethyl. The general formula (I) is shown in the specification.
- -
-
Paragraph 0209; 0363; 0366; 0367
(2016/10/20)
-
- One-Pot Three-Component Synthesis of Vicinal Diamines via In Situ Aminal Formation and Carboamination
-
A synthesis of vicinal diamines via in situ aminal formation and carboamination of allyl amines is reported. Employing highly electron-poor trifluoromethyl aldimines in their stable hemiaminal form was key to enable both a fast and complete aminal formation as well as the palladium-catalyzed carboamination step. The conditions developed allow the introduction of a wide variety of alkynyl, vinyl, aryl, and hetereoaryl groups with complete regioselectivity and high diastereoselectivity. The reaction exhibits a high functional-group tolerance. Importantly, either nitrogen atom of the imidazolidine products can be selectively deprotected, while removal of the aminal tether can be achieved in a single step under mild conditions to reveal the free diamine. We expect that this work will promote the further use of mixed aminal tethers in organic synthesis.
- Orcel, Ugo,Waser, Jerome
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supporting information
p. 12881 - 12885
(2016/10/04)
-
- PYRIDINE- AND PYRIMIDINECARBOXAMIDES AS CXCR2 MODULATORS
-
There is disclosed pyridine-and pyrimidinecarboxamide compounds useful as pharmaceutical agents, synthesis processes, and pharmaceutical compositions which include pyridine-and pyrimidinecarboxamides compounds. More specifically, there is disclosed a genus of CXCR2 inhibitor compounds that are useful for treating a variety of inflammatory and neoplastic disorders.
- -
-
Paragraph 0173
(2015/11/27)
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- Hit-to-lead optimization of disubstituted oxadiazoles and tetrazoles as mGluR5 NAMs
-
Here we report the discovery and early SAR of a series of mGluR5 negative allosteric modulators (NAMs). Starting from a moderately active HTS hit we synthesized 3,5-disubstituted-oxadiazoles and tetrazoles as mGluR5 NAMs. Based on the analysis of ligand e
- Wágner, Gábor,Wéber, Csaba,Nyéki, Olga,Nógrádi, Katalin,Bielik, Attila,Molnár, László,Bobok, Amrita,Horváth, Attila,Kiss, Béla,Kolok, Sándor,Nagy, József,Kurkó, Dalma,Gál, Krisztina,Greiner, István,Szombathelyi, Zsolt,Keser, Gy?rgy M.,Domány, Gy?rgy
-
scheme or table
p. 3737 - 3741
(2010/08/20)
-
- Pyridine- and Pyrimidinecarboxamides as CXCR2 Modulators
-
There is disclosed pyridine- and pyrimidinecarboxamide compounds useful as pharmaceutical agents, synthesis processes, and pharmaceutical compositions which include pyridine- and pyrimidinecarboxamides compounds. More specifically, there is disclosed a genus of CXCR2 inhibitor compounds that are useful for treating a variety of inflammatory and neoplastic disorders.
- -
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Page/Page column 48
(2010/08/22)
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- Synthesis of 6- and 7-membered cyclic enaminones: Scope and mechanism
-
Six- and seven-membered cyclic enaminones can be prepared using common, environmentally benign reagents. Amino acids are used as synthetic precursors allowing diversification and the incorporation of chirality. The key reaction in this multistep process involves deprotection of Boc-amino ynones and subsequent treatment with methanolic K2CO3 to induce cyclization. A β-amino elimination side reaction was identified in a few labile substrates that led to either loss of stereochemical purity or degradation. This process can be mitigated in specific cases using mild deprotection conditions. NMR and deuterium-labeling experiments provided valuable insight into the workings and limitations of this reaction. Although disguised as a 6-endo-dig cyclization, the reagents employed in the transformation play a direct role in bond-making and bond-breaking, thus changing the mode of addition to a 6-endo-trig cyclization. This method can be used to construct an array of monocyclic and bicyclic scaffolds, many of which are found in well-known natural products (e.g., indolizidine, quinolizidine, and Stemona alkaloids).
- Niphakis, Micah J.,Turunen, Brandon J.,Georg, Gunda I.
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supporting information; scheme or table
p. 6793 - 6805
(2010/12/20)
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- Synthesis of a model compound of corydendramine a via a julia coupling
-
The synthesis of the tetraenylpiperidine 12, which has the same core structure as the natural product corydendramine A, has been completed in eight steps starting from 2-piperidinemethanol 3 and trans,trans-2,6-nonadienal 6. The key step of the synthesis was a Julia coupling of sulfone (10) with aldehyde (5) to form a conjugated triene.
- McCrea-Hendrick, Maddy,Nichols, Christopher J.
-
experimental part
p. 3611 - 3620
(2009/12/09)
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- TETRAZOLE DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
-
The present invention relates to new compounds of formula (I) wherein Y1 and Y2 selected from the group consisting of hydrogen, halogen atom, C1-4 alkyl, C1-4 alkoxy or cyano group, X is oxygen or two hydrogen a
- -
-
Page/Page column 24
(2008/06/13)
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- MGLUR5 MODULATORS II
-
The present invention is directed to novel compounds, to a process for their preparation, their use in therapy and pharmaceutical compositions comprising the novel compounds.
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Page/Page column 10
(2008/06/13)
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- MGluR5 modulators I
-
The present invention is directed to novel compounds, to a process for their preparation, their use in therapy and pharmaceutical compositions comprising the novel compounds.
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Page/Page column 11
(2008/06/13)
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- FUSED THIOPHENE DERIVATIVES AS KINASE INHIBITORS
-
A series of 5,6-dihydro-1-benzothiophen-7(4H)-one derivatives, and analogues thereof, which are substituted in the 2-position by an optionally substituted morpholin-4-yl moiety, being selective inhibitors of PI3 kinase enzymes, are accordingly of benefit in medicine, for example in the treatment of inflammatory, autoimmune, cardiovascular, neurodegenerative, metabolic, oncological, nociceptive or ophthalmic conditions.
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-
Page/Page column 57-58
(2008/06/13)
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- ACYCLIC 1,4-DIAMINES AND USES THEREOF
-
This invention relates to novel compounds useful in the treatment of diseases associated with TRPV4 channel receptor. More specifically, this invention relates to certain acyclic diamines, which are agonists of TRPV4 channel receptors.
- -
-
Page/Page column 49; 144-145
(2008/06/13)
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- AZOLE-BASED PHOSPHODIESTERASE INHIBITORS
-
The present invention relates to phosphodiesterase (PDE) type IV selective inhibitors. Processes for the preparation of disclosed compounds of Formula (I), pharmaceutical compositions containing the compounds described herein and their use as PDE type IV selective inhibitors are provided.
- -
-
-
- Novel gamma-lactams as beta-secretase inhibitors
-
There is provided a series of novel substituted gamma-lactams of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R1, R2, R4, R5 and R6 as defined herein, their ph
- -
-
Page/Page column 23
(2010/10/20)
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- TRICYCLIC COMPOUND, PROCESS FOR PRODUCING THE SAME, AND USE
-
A compound of the formula: wherein R1 is a 5- or 6-membered ring; ???Z1 is a 5- or 6-membered aromatic ring; ???Z2 is a group of -Z2a-W2-Z2b-, wherein Z2a and Z2b are each O, S(O)q (wherein q is 0, 1 or 2), an imino group, or a bond; and W2 is an alkylene chain; ???W is a group represented by wherein R3 and R3' are each a hydrogen atom, a lower alkyl group, or a lower alkoxy group; X is CH or N; n and n' are each an integer of 0 or 1 to 4; m and m' are each 1 or 2; Y is O, S(O)p (wherein p is 0, 1 or 2), CH2 or NR4 (wherein R4 is a hydrogen atom, a lower alkyl group, or a lower acyl group); and ???R2 is (1) an amino group, in which the nitrogen atom may be converted to a quaternary ammonium or an oxide, or (2) a nitrogen-containing heterocyclic group which may contain a sulfur atom or an oxygen atom as the ring-constituting atom, in which the nitrogen atommay be converted to a quaternary ammonium or an oxide; or a salt thereof. The compound exhibits excellent CCR antagonist activity against CCR5, and is useful as a prophylactic and/or therapeutic agent for HIV infection in human peripheral blood mononuclear cells, especially for AIDS.
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-
Page/Page column 43-44
(2010/02/14)
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- NITROGENOUS HETEROCYCLIC DERIVATIVE HAVING 2,6-DISUBSTITUTED STYRYL
-
The invention provides a novel nitrogen-containing heterocyclic derivative having 2,6-disubstituted styryl and a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the nitrogen-containing heterocyclic derivative and a pharmaceutically acceptable salt thereof, in particular, a pharmaceutical composition effective as a sodium channel inhibitor, having an excellent analgesic action especially on neuropathic pain with minimized side effects.
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-
Page/Page column 48
(2010/02/14)
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- Investigations concerning the organolanthanide and group 3 metallocene-catalyzed cyclization-functionalization of nitrogen-containing dienes
-
Organolanthanide catalyzed cyclization-silylation of nitrogen-containing polyunsaturated systems allows access to core structures commonly found in naturally occurring alkaloids. Nitrogen-containing dienes with various substitution patterns were investigated. The method was most successful for substrates with terminal alkenes. Cyclization upon pendant 1,1-disubstituted olefins was not realized under various conditions. Interestingly, sterically hindered sulfonamides, which were previously believed to render the catalyst inactive, were actually compatible with the catalyst, thus affording the cyclized products after prolonged reaction times. Variations using fused ring systems were also investigated.
- Molander, Gary A.,Romero, Jan Antoinette C.
-
p. 2631 - 2643
(2007/10/03)
-
- POLYHETEROCYCLIC COMPOUNDS AND THEIR USE AS METABOTROPIC GLUTAMATE RECEPTOR ANTAGONISTS
-
The present invention relates to new compounds of formula (I), wherein P, Q, X1, X2, X3, X4, X5, X6, R1, R2, R3, m, n, and p are as defined as in formula (I), or salts, or hydrates thereof, processes for their preparation and new intermediates used in the preparation thereof, pharmaceutical compositions containing said compounds and to the use of said compounds in therapy.
- -
-
Page/Page column 41
(2010/02/13)
-
- Synthesis and structure-activity relationships of novel IKK-β inhibitors. Part 2: Improvement of in vitro activity
-
A series of 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl)pyridine derivatives was synthesized and evaluated as IκB kinase β (IKK-β) inhibitors. Substitution of an aminoalkyl group for the aromatic group at the 4-position on the core pyridine ring resulted i
- Murata, Toshiki,Shimada, Mitsuyuki,Kadono, Hiroshi,Sakakibara, Sachiko,Yoshino, Takashi,Masuda, Tsutomu,Shimazaki, Makoto,Shintani, Takuya,Fuchikami, Kinji,Bacon, Kevin B.,Ziegelbauer, Karl B.,Lowinger, Timothy B.
-
p. 4013 - 4017
(2007/10/03)
-
- Design and synthesis of conformationally constrained 3-(N-alkylamino) propylphosphonic acids as potent agonists of sphingosine-1-phosphate (S1P) receptors
-
A series of conformationally constrained analogs of 3 were synthesized and evaluated as S1P receptor agonists. Several novel scaffolds were identified as suitable for further investigation. A series of conformationally constrained 3-(N-alkylamino)propylphosphonic acids were systematically synthesized and their activities as S1P receptor agonists were evaluated. Several pyrrolidine and cyclohexane analogs had S1P receptor profiles comparable to the acyclic lead compound, 3-(N-tetradecylamino)propylphosphonic acid (3), lowered circulating lymphocytes in mice after iv administration and were thus identified as being suitable for further investigations.
- Yan, Lin,Hale, Jeffrey J.,Lynch, Christopher L.,Budhu, Richard,Gentry, Amy,Mills, Sander G.,Hajdu, Richard,Keohane, Carol Ann,Rosenbach, Mark J.,Milligan, James A.,Shei, Gan-Ju,Chrebet, Gary,Bergstrom, James,Card, Deborah,Rosen, Hugh,Mandala, Suzanne M.
-
p. 4861 - 4866
(2007/10/03)
-
- Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase
-
Syntheses and evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2- imines as inhibitors of nitric oxide synthase (NOS) are discussed. An extensive SAR was established for pyrrolidin-2-imines class of compounds. The amidines came out as the most potent inhibitors in addition to displaying selectivity.
- Shankaran,Donnelly, Karla L.,Shah, Shrenik K.,Guthikonda, Ravindra N.,MacCoss, Malcolm,Humes, John L.,Pacholok, Stephen G.,Grant, Stephan K.,Kelly,Wong
-
p. 4539 - 4544
(2007/10/03)
-
- Chemokine receptor binding heterocyclic compounds with enhanced efficacy
-
The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
- -
-
Page/Page column 12-13
(2010/02/03)
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- Rigidified acetylcholine mimics: Conformational requirements for binding to neuronal nicotinic receptors
-
Rigidified derivatives have been designed and synthesized assuming the g+t conformer of acetylcholine (N-C-C-O=+60°, C-C-O-C=180°) as active conformation for binding to cytisine sensitive neuronal nicotinic receptors. The SAR of the compounds evaluated, along with those of more flexible analogues, support the g+t conformer hypothesis and highlight the stringent steric limitation of this nicotinic receptor sub-type. Compound 3e has low μM affinity for cytisine sensitive nicotinic receptor binding sites while being selective with regard to the α-bungarotoxin sensitive subclass. We also report few compounds with μM affinity for the α-bungarotoxin sensitive subclass.
- Villeneuve, Gerald,Cecyre, Danielle,Lejeune, Helene,Drouin, Marc,Lan, Ruoxi,Quirion, Remi
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p. 3847 - 3851
(2007/10/03)
-
- Solenopsin derivatives and analogues as fire ant suppressants
-
The present invention relates to solenopsin alkaloid derivatives which are trans-2,6-disubstituted piperidines according to the structure: wherein R1and R2are selected from a C1to C20saturated or unsaturated linear, cyclic or branch-chained substituted or unsubstituted hydrocarbon group or a substituted or unsubstituted aromatic group, or an ester group. In certain preferred embodiments, where R1or R2contains an unsaturated group, such as an alkenyl group, the double bond in the alkenyl group preferably is found in the hydrocarbon chain between the carbon atom bonded to the piperidine ring and the adjacent carbon atom (α and β carbons).
- -
-
-
- Pyrrolidinic and piperidinic ring fission by conjugate elimination
-
Treating N-substituted pyrrolidines and piperidines bearing an allylic chain α to the nitrogen with strong bases leads to the opening of the heterocycle and provides 1,3-dienes disubstituted with an alkoxy and an aminoalkyl chain. The effects of the base and the solvent have been studied, as well as the influence of the ring size and the nitrogen substituent. The results obtained suggest a possible pre-chelation of the base cation before the deprotonation.
- Acquadro, Francesco,Oulyadi, Hassan,Venturello, Paolo,Maddaluno, Jacques
-
p. 8759 - 8763
(2007/10/03)
-
- CCR3 antagonists: a potential new therapy for the treatment of asthma. Discovery and structure-activity relationships.
-
CCR3 antagonist leads with IC(50) values in the microM range were converted into low nM binding compounds that displayed in vitro inhibition of human eosinophil chemotaxis induced by human eotaxin. In particular, 4-benzylpiperidin-1-yl-n-propylureas and erythro-3-(4-benzyl-2-(alpha-hydroxyalkyl)piperidin-1-yl)-n-propylureas (obtained via Beak reaction of N-BOC-4-benzylpiperidine) exhibited single digit nanomolar IC(50) values for CCR3.
- Wacker, Dean A,Santella 3rd., Joseph B,Gardner, Daniel S,Varnes, Jeffrey G,Estrella, Melissa,DeLucca, George V,Ko, Soo S,Tanabe, Keiichi,Watson, Paul S,Welch, Patricia K,Covington, Maryanne,Stowell, Nicole C,Wadman, Eric A,Davies, Paul,Solomon, Kimberly A,Newton, Robert C,Trainor, George L,Friedman, Steven M,Decicco, Carl P,Duncia, John V
-
p. 1785 - 1789
(2007/10/03)
-
- A new entry to 9-azabicyclo[3.3.1]nonanes using radical translocation/cyclisation reactions of 2-(but-3-ynyl)-1-(o-iodobenzoyl)piperidines
-
The 2-[4-(trimethylsilyl) but-3-ynyl]piperidines 16a-c, upon treatment with tributyltin hydride in the presence of azoisobutyronitrile in refluxing toluene, gave the 9-azabicyclo[3.3.1]nonanes 17a-c in high yields, respectively. Compound 17c was subjected to desilylation, ozonolysis, and subsequent 1,2-transposition of the resulting carbonyl group to give 9-benzoyl-1-methyl-9-azabicyclo[3.3.1]nonan-3-one, a potential precursor for the synthesis of (±)-euphococcinine.
- Sato, Tatsunori,Yamazaki, Taro,Nakanishi, Yumi,Uenishi, Jun-ichi,Ikeda, Masazumi
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p. 1438 - 1443
(2007/10/03)
-
- New entry to alicyclic amines via alkylative fragmentation of cyclic aminoaldehyde tosylhydrazones
-
Tosylhydrazones of cyclic aminoaldehydes when exposed to aromatic and aliphatic Grignard reagents produce ring-opened acyclic unsaturated primary carbamates and carbamate alcohols in good yields. (C) 2000 Elsevier Science Ltd.
- Chandrasekhar,Reddy,Rajaiah
-
p. 10131 - 10134
(2007/10/03)
-
- Total synthesis of (+)-aloperine. Use of a nitrogen-bound silicon tether in an intramolecular diels-alder reaction
-
Enantioselective total syntheses of aloperine (1), N-methylaloperine (2), and N-allylaloperine (3) are reported. The central element of the synthetic strategy is an intramolecular Diels-Alder reaction in which the cycloaddends are tethered by a N-silylamine linkage. The total synthesis of 1 proceeds from commercially available 3-hydroxypiperidine hydrochloride (54) and (R)-pipecolinic acid (35) by way of nine isolated and purified intermediates. The synthesis is sufficiently efficient that gram quantities of (+)-aloperine (1) can be readily prepared. Early exploratory studies also introduced a convenient method for tethering cycloaddition partners with a sulfonamide unit to realize the intramolecular Diels-Alder cycloaddition of a vinylsulfonamide: 45 → 46.
- Brosius, Arthur D.,Overman, Larry E.,Schwink, Lothar
-
p. 700 - 709
(2007/10/03)
-
- Intramolecular aziridination: Decomposition of diazoamides with tethered imino bonds
-
(Matrix presented) Of three possible mechanistic pathways, tethered oximino ethers react intramolecularly with diazoamides to produce a diazabicyclo[5.1.0]-hexane aziridine containing skeleton. Several acyclic and cyclic templates were synthesized and reacted with rhodium catalysts to prepare their corresponding annulated aziridines. Anomalous behavior was discovered with the piperidine template, resulting in an aziridination occurring during the attempted diazo-transfer reaction, rather than the catalyzed carbenoid reaction.
- Wright, Dennis L.,McMills, Mark C.
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p. 667 - 670
(2008/02/14)
-
- PEPTIDYL HETEROCYCLES USEFUL IN THE TREATMENT OF THROMBIN RELATED DISORDERS
-
Compounds of the Formula I: STR1 useful in the treatment of thrombin and trypsin related disorders.
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-
-
- A metallocarbenoid approach to the formation of spirocyclic ammonium ylides leading to the preparation of medium-sized azacane rings
-
A novel approach to azacyclooctene and azacyclononene containing substrates has been achieved via the intermediacy of a spirocyclic ammonium ylide derived from the diazodecomposition of a tethered α-diazoester moiety.
- Wright, Dennis L.,Weekly, R. Matt,Groff, Royce,McMills, Mark C.
-
p. 2165 - 2168
(2007/10/03)
-
- α-Lithioamine Synthetic Equivalents: Synthesis of Diastereoisomers from Boc Derivatives of Cyclic Amines
-
Sequences of α'-lithiations and electrophilic substitutions of Boc-pyrrolidines, Boc-piperidines, and Boc-hexahydroazepines that provide compounds which are substituted adjacent to nitrigen are reported, and the pathways of the reactions are discussed.By this methodology monosubstituted 2 and disubstituted 2,4, 2,6, and 2,5 Boc-piperidines are obtained as single or separable diastereoisomers consistent with equatorial lithiations and retentive electrophilic substitution in chair conformations.Both cis and trans 2,6-disubstituted diastereoisomers can be prepared, and control of diastereoselectivity is demonstrated by syntheses of solenopsin A, a 2,6-trans-disubstituted piperidine, and of Boc-dihydropinidine, a 2,6-cis-disubstituted piperidine.In the case of 3-methoxy-Boc-piperidine elimination of methoxide occurs upon lithiation, and with cis-2,4-disubstituted Boc-piperidines the electrophile is introduced with trans stereochemistry at C-6.These reactions are suggested to involve twist boat conformations consistent with an X-ray crystal structure of 2-methyl-6-(trimethylstannyl)-4-phenyl-N-Boc-piperidine.Boc-pyrrolidine lithiates more rapidly than Boc-piperidine, provides 2-substituted products with electrophiles, and on further lithiation-substitution gives 2,5-cis- and -trans substituted products.Boc-perhydroazepine provides 2-substituted products by the sequence and on further lithiation-substitution gives 2,7-trans-disubstituted products.
- Beak, Peter,Lee, Won Koo
-
p. 1109 - 1117
(2007/10/02)
-
- Thermally Induced Intramolecular Oxime Olefin Cycloadditions (IOOC) Leading to N-Bridgehead Systems. Stereochemistry and Molecular Mechanics Calculations
-
The intramolecular oxime olefin cycloaddition (IOOC) of proline and pipecolinic acid derivatives proceeds thermally with a high degree of stereoselectivity to provide a new route to functionalized pyrrolizidines, indolizidines, or quinolizidines.The ring closure proceeds with simultaneous stereoselective introduction of three or four stereocenters.Molecular mechanics calculations have been refined to accurately predict not only which stereoisomer is preferred but also the syn and anti coupling constants in these tricyclic molecules.
- Hassner, Alfred,Maurya, Rakesh,Padwa, Albert,Bullock, William H.
-
p. 2775 - 2781
(2007/10/02)
-
