Elimination with DBU

Treatment of MFA (1) with cyanogen bromide [6] opened ring G to yield the bromo derivative 3 [7]. Attempts to dehydrobrominate 3 in one step via a base-catalyzed elimination with DBU/CH3CN, KOH/MeOH, or terr-BuOK/DMSO were unsuccessful. However, the required methylene entity could be introduced by converting 3 first to a selenide, then oxidation with periodate, followed by thermolysis in benzene to provide compound 4. Hydrolysis of the cyano group with NaOH in ethylene glycol [8] produced 5 (50% yield). Osmium catalyzed oxidation of 5 in the presence of 4-methylmorpholine A-oxide (NMO) gave a diol, which was cleaved to an aldehyde upon treatment with periodate. Treatment of the aldehyde with sodium cyanoborohydride resulted in an intramolecular reductive animation to yield the desired product PHB (6). 

Napieralski cyclization by heating with POCl3 in xylene followed by methanolic workup and saponification of the acetate groups. After selective tosylation of the hydroxyl group at C-2 on 551 usingp-toluenesulfonyl chloride in pyridine, base-induced elimination with DBU in DMSO and hydrolysis of the A, O-acetal with 50% aqueous acetic acid then produced ( )-haemanthidine (382) (2/5). 

Model studies directed towards the installation of the phosphate monoester in Calyculin A [Scheme 7.34] established that -elimination with DBU alone led to loss of only one of the cyanoethyl groups because the initial anionic phosphate product resists attack by the base.70 However, use of DBU in the presence of chlorotrimethylsilane resulted in complete elimination. Presumably O-silyEation of the intermediate phosphate facilitates the second elimination ... 

From a preparative standpoint, protection of the weak acidic OH group by an acyl or silyl protecting group not only facilitated separation and isolation but also improved the base-mediated elimination with DBU. The whole sequence was thus applied to O-protected quinine and related QCI and QCD (Scheme 12.18). 

Though milder conditions (NaOH, Et20) gave 42 in 86% yield, this was of course racemic. The single enantiomer was made from tartaric acid 47 by conversion into the enone 48, conjugate addition of a lithium cuprate with excellent anti-selectivity 49 and elimination with DBU.14... 

The starting material is natural P-cyclocitral 76, converted to its methyl acetal 78. The extended enolate 77 is best realised as the silyl enol ether 79 and reaction with 78 followed by base gives the trienal 75. Repetition of the three steps gives all E retinal 74. The two extended aldol reactions go in excellent yield with total regioselectivity, only the base-catalysed eliminations with DBU are disappointing. 

Epoxide 109 is opened with Me3SiBr (Ph3P-catalysed) and another elimination with DBU gives the allylic alcohol 117. The epoxidation that follows is controlled in a couple of ways. Firstly, the axial alcohol can direct the reagent (the same peroxyacid used to make 109) to the bottom face of the six-membered ring which is also the less hindered side of the molecule (opposite the lactone bridge) 118. The synthesis is completed with basic methanolysis of the lactone 118 to give racemic methyl shikimate 116. 

This is not important as deacylation destroys that centre anyway 32. Epoxidation followed the best route was bromohydrin formation with NBS in water followed by elimination with DBU and gave an 8 1 selectivity for epoxidation on the opposite face to the substituent 33. 

Palladium(II)-promoted alkenylation involving a-bromo sulfonamide has been utilized to construct the bridgehead bicyclic sultam 193 <04OL1313>. Treatment of 192 with palladium acetate in DMF containing K2CO3, tri-2-furylphosphine and 4A molecular sieves at 100 C furnishes 193. Subsequent bromination with NBS and elimination with DBU give rise to conjugated diene 194. When irradiated at 350 nM, 194 is isomerized via a two-photon process to the structurally novel spiro heterocycle 198. 

Treatment of 51 with an excess of sodium benzoate in DMF resulted in substitution and elimination, to yield the cyclohexene derivative (228, 36%). The yield was low, but 228 was later shown to be a useful compound for synthesis of carba-oligosaccharides. <9-Deacylation of228 and successive benzylidenation and acetylation gave the alkene 229, which was oxidized with a peroxy acid to give a single epoxide (230) in 60% yield. Treatment of 230 with sodium azide and ammonium chloride in aqueous 2-methoxyeth-anol gave the azide (231,55%) as the major product this was converted into a hydroxyvalidamine derivative in the usual manner. On the other hand, an elimination reaction of the methanesulfonate of 231 with DBU in toluene gave the protected precursor (232, 87%) of 203. 

The synthesis of 2,3,5-trialkylpyrroles can be easily achieved by conjugate addition of nitroalkanes to 2-alken-l,4-dione (prepared by oxidative cleavage of 2,5-dialkylfuran) with DBU in acetonitrile, followed by chemoselective hydrogenation (10% Pd/C as catalyst) of the C-C- double bond of the enones obtained by elimination of HN02 from the Michael adduct. The Paal-Knorr reaction (Chapter 10) gives 2,3,5-trialkylpyrroles (Eq. 4.124).171... 

The dianion derived from methyl 3-nitropropanoate is formed on treatment with LDA, and it is alkylated by alkyl halides exclusively at the 2-position (Eq. 5.6). Elimination of HN02 with DBU in THF furnishes methyl a-methylenealkanoate (see Section 7.3, which discusses alkene formation).12... 

When treated with DBU at elevated temperature, l-[(benzotriazol-l-yl)methyl -2-aminopyridine salts 741 eliminate rather the N-H proton than the C-H one. Intermediates 742 can be trapped with aromatic aldehydes to create betaines 743. The consecutive cyclocondensation and elimination of benzotriazole results in formation of imidazolo[l,2-rz]pyridines 744 in good yields (Scheme 117) <2000JOC9201>. Aldehydes with enolizable a-protons fail to give bicyclic systems 744, producing corresponding enamines instead. 

Transformations of Methyl 5-0-Benzyl-2-0-methyl-/3-I)-glueofuranosidurono-6,3-lae-tone (86) to Dimethyl (Z,E)-2-Methoxy-5-(phenylmethoxy)-2,4-hexadienedioatevl (87). ( Elimination employing DBU b oxidation with silver oxide-sodium hydroxide followed by diazomethane esterification c acidic glycoside cleavage, oxidation by dimethyl sulfoxide-acetic anhydride with formation of 5-0-benzyl-2-0-methyI-D-glucaro-1,4 6,3-dilactone, elimination by using DBU, followed by short treatment with diazomethane d elimination by DBU with subsequent diazomethane esterification e sodium borohydride in hexamethylphosphoric triamide 1 catalytic oxidation followed by short treatment with diazomethane " dimethyl sulfoxide-sulfur trioxide-pyridine-triethylamine.150)... 

Elimination.1 The dehydroiodination of y-iodo ketones or y-iodo esters with DBU at 25° to form cyclopropanes occurs readily only when the proton and the iodo group can adopt a W-shaped geometry. Thus the cyclopropane 1 is formed... 

A two-step sequence to prepare di-O-acetyl-3-deoxy-D-arabino-l, 4-lactone from tri-O-acetyl-D-ribono-1,4-lactone has also been reported, but in a low yield of 46% because ol the difficulty of controlling the elimination of the 3-acetoxy group, since the 2,3-unsaturated lactone also undergoes further elimination.5 Furthermore, partial racemization of the enolizable 2,3-unsaturated lactone could occur during treatment with DBU.6... 

Reaction of the TMS-nitro compound 1496 and the indole carboxaldehyde 1497 with a catalytic amount of TBAF led to the desired alcohol 1498, which, on further treatment with TFAA, followed by elimination of the corresponding trifluoroacetate with DBU, afforded the frans-stilbene 1499. Reductive cyclization of 1499 under Cadogan-Sundberg conditions afforded the bisindole 1500. Finally, condensation of 1500 with (dimethylamino)acetaldehyde diethyl acetal led to tjipanazole D (359) in 71% yield (796) (Scheme 5.255). 

Synthesis of the polymer-bound allyl sulfoximine 60 was accomplished by the addition-elimination-isomerization route starting from the enantiomerically pure polymer-bound N-methyl-S-phenylsulfoximine 59, which was prepared as previously described from Merrifield resin and sulfoximine 12 with a loading of 84% (Scheme 1.3.23) [42]. The successive treatment of resin 59 with n-BuLi in THF and with isovaleraldehyde furnished the corresponding polymer-bound lithium alcoholate, which upon reaction with ClC02Me and DBU afforded the corresponding polymer-bound vinylic sulfoximine (not shown in Scheme 1.3.23), the isomerization of which with DBU in MeCN afforded sulfoximine 60. 

Treatment of 15 with l,5-diazabicyclo[5.4.0]undec-5-ene (DBU) in benzene resulted in /3-elimination, but under these conditions, the liberated 2,3,4,6-tetra-O-methyl-D-glucose was further degraded, probably with formation of 3-deoxy-2,4,6-tri-0-methyl-D-erc/fhro-hex-2-enopyranose. In order to prevent this degradation, the reaction of 15 with DBU was carried out in the presence of acetic anhydride. The reaction mixture gave, after chromatography on silica gel, methyl (methyl 4-deoxy-2,3-di-0-methyl-a-L-threo-hex-4-enopyranosid)uron-ate (65) and a mixture of the 1-acetates of 2,3,4,6-tetra-O-methyl-a- and -/3-D-glucose (66). 

Dehydrobromination. Dehydrobromination with AgF-pyridine was first reported some time ago.1 It has recently proved to be the method of choice in a total synthesis of thienamycin, a carbapenem broad-spectrum antibiotic. I- or example, attempted dehydrobromination of 1 with DBU in DMSO resulted in elimination of HBr and also carbonate to give a mixture (2) of two ene lactams. The desired reaction was effected in 70% yield with AgF in pyridine.2... 

A 3-Phosphorin derivatives of benzo annelated rings were intensively studied by Bickel-haupt and coworkers. One of his preferred methods consists in the introduction of the final P=C double bond from appropriate ring systems by basic elimination of HC1 with DBU or other bases. Many benzo-A 3- phosphorins have been reported. An example is the synthesis of 2-phosphanaphthalene (equation 26) (75T1097). Some other examples are shown in (32)-(35). 

Similar procedures can be used to prepare AAbu (both E- and Z-isomers) from Thr derivatives. Srinivasan et al/891 found that (3-elimination of the Thr derivative, Ac-(2R,35)-Thr-OMe 37 (threo type), gave only the stable Z-isomer 38 upon O-tosylation and subsequent elimination by DABCO as a base (Scheme 14). The underlying mechanism for this reaction may be a traits E2-elimination. (25,3R)-2-Acetamido-3-chlorobutanoic add methyl ester (erythro) 39, derived from the Thr threo form by chlorination with inversion of configuration at the (3-carbon, yields predominantly the E-isomer 38 by brief treatment with DBU as a base. However, a prolonged reaction time and use of DABCO as a base causes a significant amount of isomerization to the Z-isomer. 

Mixed bromides 33, 34 formed from either 1 -0-acetyl-2,3,5,6-tetra-O-benzoyl-/ -D-glucose or -galactose, also undergo preferential endo-elimina-tion on treatment with DBU, and give the alkene (170). As in the pyranose series, exo-elimination is favored with use of zinc - acetic acid, and geometric isomers (171) are the main products and are formed93 together with the 3-deoxy-3-ene (172). 

For example, the reaction of 3-chlorocyclohexanone with DBU in toluene gives a product which is seen to have two vinyl protons by NMR and thus is an elimination product, probably either A or B. Now while one might rationalize by both chemical intuition and by the splitting pattern that conjugated isomer A is the product, examination of the IR spectrum shows a carbonyl group (at 1680 cm-1) and an olefin band (at 1630 cm-1). A typical cyclohexanone comes at 1710 cm-1 and cyclohexene comes at 1643 cm-1. 

Elimination reactions of ( )- and (Z)-benzaldehyde Opivaloyloximes (19a) and (19b) with DBU in MeCN have been found to occur by a nitrile-forming E2 mechanism which is ca 2000-fold faster for the latter isomer in each case.15 The corresponding Hammett substituent constants, activation parameters, and primary deuterium isotope effects, suggest that the anti elimination from (19b) (for which p = 2.4 0.1, H/ D = 2.7 0.3, A/H = 12.5 0.2 kcal mol-1, and A= —31.0 0.6eu) proceeds to (20) via a more symmetrical transition state with a smaller degree of proton transfer, less charge development at the jS-carbon and greater extent of triple bond formation than for syn elimination from (19a) (for which p = 1.4 0.1, kn/kn = 7.8 0.3, AH = 8.8 0.1 kcal mol 1 and A= -23.6 0.4 eu). 

Bromo-enamides have been reported to give radical cyclization in excellent yields (82-99%) to p-lactams using catalytic amounts (30%) of tripyridylamine (TPA) copper halide complex [184]. The p-lactam developed under mild conditions via 4-exo bromine atom transfer and subsequent elimination of the tertiary bromide that could be readily achieved by reaction with DBU (Scheme 83). 

Further, medium-sized lactones have been prepared by a thermal elimination-Claisen rearrangement sequence, of unsaturated selenoxide cyclic acetals (equation 198)710. The reaction affords reasonable yields of these useful lactones upon treatment with DBU and a siloxy species at 185 °C. The reaction has been used as the key step in the synthesis of (-l-)-laurencin, which contains an 8-membered cyclic ether moiety711. 

PhosphorylationThis reagent can be used for 3 -and/or 5 -phosphorylation of nucleosides in the phosphotriester approach to oligonucleotides. Deblocking by / -elimination proceeds cleanly with DBU in pyridine at 25" in 24 hours. 

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