Ketenes were first studied as a class by Hermann Staudinger
Pyrimidine - Wikipedia
WITTIG REACTION | MECHANISM | ADICHEMISTRY
The completion of the synthesis was now trivial. Acylation of 46 with 3-methyl-2-butenoyl chlorideand NaH in THF at 25 °C for 2 h gave 58, which was stirred in 9:1 CH2Cl2/TFA for 15 h to give (±)-NP25302 (12) in 88% yield from 46.
In an effort to illustrate the potential utility of our method in natural product synthesis, (Z)-trisubstituted allylic alcohol 18, which is an intermediate in the total synthesis of (−)-hennoxazole A and a fragment common to the natural products (+)-migrastatin and (+)-discodermolide, was synthesized., A modified Corey-Fuchs procedure, was employed to convert aldehyde 16 into enantioenriched 1-bromo-1-alkyne 17 in two steps. Subjecting bromoalkyne 17 to hydroboration, 1,2-metallate rearrangement/transmetallation, and addition to formaldehyde yielded the (Z)-trisubstituted allylic alcohol 18 in 73% yield without loss of ee ().
wittig reaction explained with mechanism in detail and illustrations
Another common method to generate (Z)-trisubstituted allylic alcohols involves addition of (Z)-vinylorganometallic reagents to aldehydes. The Nozaki-Hiyama-Kishi (NHK) reaction would appear to be one such example. Although it has been elegantly used in complex molecule syntheses, it suffers from several drawbacks. These include the toxicity of chromium, which is often used in catalytic amounts. Although conservation of the double bond geometry of the vinyl iodides or triflates is usually very good, (Z)-trisubstituted vinyl iodides and triflates readily isomerize to the (E)-isomer under NHK conditions ().– Metallation of (Z)-vinyliodides with n-BuLi or i-PrMgBr followed by addition to chiral aldehydes is also attractive, but usually proceeds with reduced diastereoselectivity due to the reactive nature of these organometallic reagents ()., Alternatively, softer nucleophiles based on Zn and Al, various additives, and Lewis acids are often employed to increase the selectivity.– These methods are dependent on availability of (Z)-vinyl iodides with high stereochemical purity.
We now turned to the synthesis of jenamidines A1/A2 (8), which required the development of new methods for the preparation of the novel N-acyl vinylogous urea in the right hand ring. A wide variety of approaches proved to be unsuccessful. For instance, we attempted to convert the known keto lactam 15 to enol triflate 14a, which should undergo Pdcatalyzed amidation as recently reported for related systems (see ). Unfortunately, reaction of 15 with NaH and Tf2O gave only the unstable pyrrole bis triflate 16. Use of excess NaH and Tf2O gave crude (90% pure) 16 in 91% yield, which was isolated in only 17% yield. Although we could cleanly couple 2-methyl-2-butenamide with the enol triflate prepared from dimedone, initial attempts at Pd-catalyzed couplings of amides with 16 were unsuccessful. Attempted preparation of vinylogous urea 14b by reaction of keto lactam 15 with NH3 gave complex mixtures that did not contain 14b.
ALDOL REACTION | ADDITION | CONDENSATION | …
The A-rings of calcitriol (1α,25-dihydroxyvitamin D3) and 1α-hydroxy-3-deoxyvitamin D3 were synthesized using the furan approach. The critical steps in the synthesis of the A-ring of calcitriol involved an asymmetric carbonyl-ene reaction of 3-methylene-2,3-dihydrofuran with 3-(-butyldimethylsiloxy)propanal, a diastereoselective Friedel−Crafts hydroxyalkylation, an oxidation of the 2,3-disubstituted furan to give a γ-hydroxybutenolide, and a Peterson olefination. The A-ring ()-dienol of calcitriol was synthesized in 12 steps from 3-(-butyldimethylsiloxy)propanal in 17% yield.
To this end, we recently reported an effective synthesis of the EF fragment of (+)-spongistatin 1 (1) via (+)-7 () exploiting the Petasis-Ferrier union/rearrangement, a synthetic tactic employed extensively in our laboratories to access cis-2,6-disubstituted tetrahydropyrans. This approach successfully provided more than 700 mg of the EF Wittig salt, which eventually led to 80 mg of spongistatin 1 (from 450 mg of the EF Wittig salt). Shortly thereafter, the MacMillan group reported an elegant two-step synthesis of carbohydrates, combining a highly enantioselective proline-catalyzed cross-aldol reaction of oxyaldehydes with a Mukaiyama aldol reaction. This approach to carbohydrates via the intermediacy of a lactone held the promise of an even more concise approach to (+)-7 possessing the requisite cis-tetrahydropyran F-ring of (+)-spongistatin 1. The potential benefits of this strategy would include: (1) a shorter reaction sequence, (2) excellent cost of goods, (3) stable intermediates, (4) simple operations, including purifications, (5) high reproducibility and efficiency, and most important, (6) scalability.
gamma-valerolactone, 108-29-2 - …
A ketene is an organic compound of the form R′R″C=C=O
Ketene - Wikipedia
Ketene also refers to CH 2 =C=O, occasionally called ethenone
How to make propanal from propene?
05/07/2010 · How to make propanal from propene
These expectations were confirmed by the synthesis of tricycle 6, which is a good model for the piperidinone moiety of the proposed structure of jenamidine A (see ). Reaction of 2,3-dihydro-4-pyridinone (4) with isatoic anhydride (5) and Et3N in THF for 8 h in a sealed tube at 80 °C provided 29% (65% based on recovered 4) of the surprisingly unstable tricyclic piperidinone 6. Analysis of the NMR spectral data of 6 confirmed our doubts regarding the structure proposed for jenamidine A. H9a of 6, which is adjacent to two nitrogens, absorbs at δ 5.12 (dd, J = 3.7, 9.2 Hz). The methylene groups adjacent to the ketone absorb between δ 2.4 and 2.6. The three CH2 carbons absorb at δ 47.8, 40.9 and 39.7. These data are consistent with those expected for this structure. Treatment of 6 with dilute acid resulted in a facile retro-Mannich reaction to give 7 quantitatively. Partial conversion of 6 to 7 occurred during flash chromatography on silica gel suggesting that structure 1 would not survive the isolation protocol for jenamidine A.
of propionaldehyde is from synthesis …
Formal synthesis of SB-311009 analogues. We isolated 23 from an unsuccessful approach to jenamidines A1/A2. While looking for analogous compounds to help us confirm the structure of 23, we came across SB-253514 (70), which was isolated by Readshaw and coworkers from the culture broths of Pseudomonas fluorescens strain DSM11579 in 2000. The glycosidic linkage was hydrolyzed enzymatically to give the alcohol SB-311009 (69) (see ). SB-253514 is a potent and selective inhibitor (IC50 = 51 nM) of lipoprotein-associated phospholipase A2 (LpPLA2), the enzyme responsible for the conversion of phosphatidylcholine to lysophosphatidylcholine and oxidized fatty acids during the conversion of low density lipoprotein to its oxidized form. Pinto prepared 74, in which R is a variety of long alkyl chains, and found that these analogues were 2−4 times more biologically active than 69 or 70. A five-step sequence converted N-Boc-proline (71) to the unsaturated 2-trimethylsilylethyl ester 72 in 7% overall yield. Deprotection of the 2-trimethylsilylethyl ester with TBAF gave acid 73 in 100% yield, which was coupled with an amine using EDCI to give 74.
Thieme E-Journals - Synthesis / Volltext
The proposed structures of jenamidines A, B, and C (1−3) were revised to jenamidines A1/A2, B1/B2, and C (8-10). Jenamidines A1/A2 (8) were synthesized from activated proline derivative 43 by conversion to 26 in two steps and 50% overall yield. Acylation of 26 with acid chloride 38d gave 39d, which was deprotected with TFA and then mild base to give 8 in 45% yield from 26. (−)-trans-2,5-Dimethylproline ethyl ester (49) was prepared by the enantioselective Michael reaction of ethyl 2-nitropropionate (51) and methyl vinyl ketone (50) using modified dihydroquinine 60 as the catalyst. Further elaboration converted 49 to natural (+)-NP25302 (12). A Wittig reaction of proline NCA (76) with ylide 79 gave 72 as a 9/1 E/Z mixture in 27% yield completing a one step formal synthesis of SB-311009 analogues.
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