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Cyclopropyl building blocks for organic synthesis part 64 - Facile preparation of hexahydropyrrolo[3,2-e][1,4]diazepine-2,5-diones and tetrahydrofuro[1H][3,2-e][1,4]diazepine-2,5-diones by rearrangements of cyclopropylketimines and cyclopropylketones
No full text[GRAPHICS] Chlorolactames 2a-f reacted with sodium azide to give the cyclopropylketimines 3a-f (75-89%), and acid hydrolysis of 3c,d yielded the cyclopropylketones 6c,d (61-67%), Compounds 3a-f and 6c,d were transformed by heating (170-240 degreesC, sublimation) to the air-sensitive dihydropyrroles 4a-f (51-71%) and dihydrofurans 7c,d (85-91%), Oxidation of the dihydro derivatives 4a-f and 7c,d with DDQ led to novel types of pyrrolo[3,2-e][1,4]diazepinedione derivatives 5a-f (75-84%) and furo[H-1][3,2-e][1,4]diazepinediones 8c,d (91-93%)
Synthesis of Spirocyclopropanated Analogues of Iprodione
No full textMethyl 1(tert-butoxycarbonylamino)cyclopropanecarboxylate (9) was converted into the spirocyclopropanated fivemembered ring analogue 7a of Iprodione (1) in five steps with an overall yield of 28 %. The spirocyclopropanated fivemembered ring analogue 8a was prepared from tert-butyl N[1-(hydroxymethyl)cyclopropyl]carbamate (10) in five steps with an overall yield of 19 %. En route to the spirocyclopropanated six-membered ring analogues of Iprodione (1), the oxalic acid diamides 5b and 6b could be obtained starting from 9 or 10 in 33 or 19 % yield, respectively. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Preparation of Cyclopropane Analogues of the Natural AntibioticTAN 1057 A/B
No full textThe two new analogues 2 and 3 of the natural dipeptide antibiotic TAN 1057 A/B (1), both with cyclopropyl containing Pamino acid side chains, were prepared. The synthesis of the corresponding beta-amino acids in appropriately protected form (4-Z(3) and 5-Z(2), respectively) from the correspondingly protected (hydroxyethyl)- (7a) and (hydroxymethyl)-substituted cyclopropylidene acetate (7b), prepared in two steps each from homoallyl and allyl benzyl ether, respectively, was achieved in nine and seven steps, respectively, with overall yields of 17 (4-Z(3)) and 9.3% (5-Z(2)), respectively. Coupling with the N-methyldihydropyrimidinone 22 and deprotection gave the compounds 2 and 3, which turned out to be active against methicillin resistant strains of Staphylococcus aureus, albeit to a lesser extent than TAN 1057 itself. (c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005
A new and efficient access to thiazoline-4-carboxylates and cysteine derivatives incorporating cyclopropyl groups
No full textUnder basic conditions (NaHCO3, MeCN), thiocarboxamides 2, including NN-thioureas, cleanly undergo Michael addition onto 2-chloro-2-cyclopropylideneacetates 1, attacking through the sulfur, and this is followed by an intramolecular substitution to afford 5-spirocyclopropane-annelated thiazoline-4-carboxylates 4 in 37-92% yields. The thiazolines 4 are cysteine derivatives that possess a cyclopropyl or substituted cyclopropyl group in place of the gem-dimethyl-substituted beta -carbon atom of penicillamine; they can be hydrolyzed to the hydrochloride salt of the amino acid 5 by heating in acid. Under acidic conditions (CH2Cl2, HCl), the Michael adducts 7 of thioamides 2 onto 1 are formed in high to virtually quantitative yields. When treated with NaHCO3 in MeCN, the adducts 7 cyclize to thiazolinecarboxylates 4 (51-82%), but in the presence of Ti(OiPr)(4) they form spirocyclopropane-annelated thiazinones 8 (19-88%)
New highly efficient three-component domino Heck-Diels-Alder reaction with bicyclopropylidene: Rapid access to spiro[2.5]oct-4-ene derivatives
No full textBicyclopropylidene (1) was found to surpass even methyl acrylate (17a) in its rate of undergoing carbopalladation with aryl- or alkenylpalladium species. leading to substituted allylidenecyclopropanes 5, 7 and 10, mostly in high yields (37 - 78%). These dienes and cross-conjugated trienes react in a Diels-Alder mode with dienophiles to give spiro[2.5]octenes 18a-Ph, 18b-Ph and 18a-Vin, respectively, in good yields (89, 69 and 65%). The overall transformation can be achieved as a one-pot three-component reaction with a variety of dienophiles to furnish the domino Heck-Diels-Alder products 18 regioselectively in most cases in good to very high yields (49-100%). The reaction of I with iodobenzene (2-Ph) and 17a gave 18a-Ph in virtually quantitative yield-also on a gram scale-using, only 1 mol% of catalyst, and even bromobenzene (22) gave 18a-Ph in 59% yield. Bicyclopropylidene (1). in the presence of palladium acetate/triphenylphosphane underwent rearrangement to allylidenecyclopropane (5-H), which in turn dimerized (73%) in the absence of other reaction partners, or could be trapped by diethyl fumarate (17c) to give the Diels-Alder adduct 18c-H in 45% yield. The coupling of oligoiodobenzenes with I and subsequent cycloaddition could he extended to a multicomponent reaction. In this way, 1.4-diiodobenzene (37). 1 and an alkyl acrylate gave the products 38 of a twofold Heck-Diels-Alder reaction in up to 87% yield, 1,3,5-triiodobenzene (39) reacted in up to 72% yield and ultimately 1,2,4,5-tetraiodobenzene (41) gave the fourfold domino Heck-Diels-Alder product 42 in 47% isolated yield, in a single operation in which 12 new carbon-carbon bonds were formed
3-azabicyclo[3.1.0]hex-1-ylamines by Ti-mediated intramolecular reductive cyclopropanation of alpha-(N-allylamino)-substituted N,N-dialkylcarboxamides and carbonitriles
No full textA variety of tris- and monoprotected derivatives with the 1-amino-3-azabicyclo[4.1.0]hexane and 1-amino-3-azabicyclo[4.1.0]heptane skeleton 10 have been synthesized by intramolecular reductive cyclopropanation of alpha-(N-allylamino)substituted N,N-dialkylcarboxamides 6, 8, and 9. Starting from derivatives of the naturally occurring amino acid serine (4a, 4b), the enantiomerically pure compounds 10a and 10b were obtained with endo/exo ratios of 2.5:1 (a) and 2:1 (b), in 26 and 30% overall yields, respectively. The unprotected bicyclic amines 11aa, 11ab, 11ba, and 11ad have been prepared by palladium-catalyzed hydrogenative deprotection of 10aa, 10ab, 10ba and 10ad, respectively, under acidic conditions, in 91, 95, 96, and 99% yields, respectively. X-ray crystal structure analyses of 10aa and 10ad in each case found an equatorial position of the N-benzyl group on the heterocycle and a common boat conformation for the 3-azabicyclo[3.1.0]hexane and 3-azabicyclo[4.1.0]heptane skeletons as a whole. One-step preparations of the bicyclic diamines I lac (41% yield) and 14a (48% yield) have been performed by application of the Kulinkovich-de Meijere procedure to the nitriles 12a and 12b
A new and efficient access to oxazoline-5-carboxylates and amino acid derivatives with cyclopropyl groups
No full textSynthesis of Spirocyclopropanated Analogues of Imidacloprid and Thiacloprid
No full texttert-Butyl N-[1-(hydroxymethyl)cyclopropyl]carbamate (8) was converted into spirocyclopropanated analogues 14-CP and 14-CT of the insecticide Thiacloprid (2) in six simple steps with overall yields of 24% each, along with their regioisomers 13-CP and 13-CT in overall yields of 17 and 15%, respectively. The spirocyclopropanated analogues 27-CP and 27-CT of the insecticide Imidacloprid (1) were prepared from 8 in five steps in an overall yield of 10% each, along with their regioisomers 20-CP and 20-CT in an overall yield of 8 and 7%, respectively. The key step in all preparations was a cocyclization of an appropiately protected (1-aminocyclopropyl)methyl derivative with S,S-dimethyl cyanodithioirninocarbonate (11) or nitroguanidine (22). The structures of several final products and by-products were verified by X-ray crystal structure analyses
Cyclopropyl building blocks for organic synthesis. Part 85. Facile preparation and chemical transformations of spirocyclopropane-annelated heterocycles
No full textA productive approach has been developed to spirocyclopropane-annelated 1,4-benzoxathiane 17 (85%), 1,4-benzothiazines 20-22 (56-88%) and 1,4-benzoxazines 25, 26 (55-71%), through Michael additions of binucleophilic o-hydroxythiophenol 15, o-aminothiophenols 8 and o-hydroxysulfanilides 23 onto methyl and tert-butyl 2-chloro-2-cyclopropylideneacetates (1-Me, 1-tBu), followed by ring closure in the intermediate of type 3 through nucleophilic substitution of the chlorine atom and, in the case of the intermediates 20, 21 and 25, elimination of benzenesulfinic acid. Reduction of 20a with LiAlH4 led to the hydroxymethyl derivative 28 (88%) with retention of the N-phenylsulfonyl group, while that of the oxazinecarboxylate 26a-Me gave the beta-amino alcohol 27 (87%). Selective reduction of the C=N double bond in 26a-Me was achieved with NaBH4 in methanol. Halogen-substituted benzoxazines 26b,c were modified further by Heck coupling with various alkenes. In the presence of a catalytic amount of triphenylphosphane, only the 6-bromobenzoxazine underwent Heck coupling accompanied by ring opening of the spirocyclopropane moiety. The best yields of cross-coupling products 30d-i (60-89%) retaining the spirocyclopropane ring were achieved for 6-iodobenzoxazine 26c-Me reacting with methyl acrylate, acrolein, and methyl vinyl ketone, respectively. By treatment with morpholine in DMF, the heterocyclic esters 26b,c undergo demethoxycarbonylation to form spirocyclopropane-annelated 1,4-benzoxazines 36b,c in high yields (83-98%). The 1,4-benzoxazine 36b readily adds nucleophiles such as p-thiocresol and hydrogen cyanide across its C=N double bond to yield compounds 37 (76%) and 38 (95%), respectively
Cyclopropyl building blocks for organic synthesis. Part 85. Facile preparation and chemical transformations of spirocyclopropane-annelated heterocycles
No full textA productive approach has been developed to spirocyclopropane-annelated 1,4-benzoxathiane 17 (85%), 1,4-benzothiazines 20-22 (56-88%) and 1,4-benzoxazines 25, 26 (55-71%), through Michael additions of binucleophilic o-hydroxythiophenol 15, o-aminothiophenols 8 and o-hydroxysulfanilides 23 onto methyl and tert-butyl 2-chloro-2-cyclopropylideneacetates (1-Me, 1-tBu), followed by ring closure in the intermediate of type 3 through nucleophilic substitution of the chlorine atom and, in the case of the intermediates 20, 21 and 25, elimination of benzenesulfinic acid. Reduction of 20a with LiAlH4 led to the hydroxymethyl derivative 28 (88%) with retention of the N-phenylsulfonyl group, while that of the oxazinecarboxylate 26a-Me gave the beta-amino alcohol 27 (87%). Selective reduction of the C=N double bond in 26a-Me was achieved with NaBH4 in methanol. Halogen-substituted benzoxazines 26b,c were modified further by Heck coupling with various alkenes. In the presence of a catalytic amount of triphenylphosphane, only the 6-bromobenzoxazine underwent Heck coupling accompanied by ring opening of the spirocyclopropane moiety. The best yields of cross-coupling products 30d-i (60-89%) retaining the spirocyclopropane ring were achieved for 6-iodobenzoxazine 26c-Me reacting with methyl acrylate, acrolein, and methyl vinyl ketone, respectively. By treatment with morpholine in DMF, the heterocyclic esters 26b,c undergo demethoxycarbonylation to form spirocyclopropane-annelated 1,4-benzoxazines 36b,c in high yields (83-98%). The 1,4-benzoxazine 36b readily adds nucleophiles such as p-thiocresol and hydrogen cyanide across its C=N double bond to yield compounds 37 (76%) and 38 (95%), respectively
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