Preparation of Weinreb Amides Using 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium Chloride (DMT-MM)

Hioki, Kazuhito; Kobayashi, Hiroko; Ohkihara, Rumi; Tani, Shohei; Kunishima, Munetaka

doi:10.1248/cpb.52.470

Cited by 22 publications

(11 citation statements)

References 18 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Products 8a, [29] 8b, [30] 8c, [30] 8d, [30] 8e, [30] 8f, [31] 8g, [32] 8h, [33] 8i, [34] 8j, [35] 8k, [29] 8l, [29,36] 10a, [37] 10b, [38] 10c, [39] 10d, [40] 10e, [38] 10f, [41] 10g, [42] 10h, [43] 10i, [43] and 10j [43] have been described previously and gave satisfactory spectroscopic and physical data. Products 8a, 10a and 10d are also commercially available.…”

Section: Methodsmentioning

confidence: 99%

3,5‐Bis(trifluoromethyl)phenyl Sulfones for the Highly Stereoselective Julia–Kocienski Synthesis of α,β‐Unsaturated Esters and Weinreb Amides

et al. 2008

View full text Add to dashboard Cite

The 3,5-bis(trifluoromethyl)phenyl (BTFP) sulfones tert-butyl α-(BTFPsulfonyl)acetate (4) and Weinreb α-(BTFPsulfonyl)-acetamide (5) have successfully been employed in the JuliaKocienski olefination of aldehydes with K 2 CO 3 as the base at 120°C in DMF under solid/liquid phase-transfer catalysis conditions to afford α,β-unsaturated esters and Weinreb amides, respectively. The corresponding products were obtained in good yields and with high E stereoselectivities (E/Z up to Ͼ99:1), especially in the case of the amides. A detailed computational study of the Julia-Kocienski olefination with BTFP sulfone 4 was carried out and confirmed the existence of an equilibrium in the initial addition of the sulfone enolate

show abstract

Section: Methodsmentioning

confidence: 99%

3,5‐Bis(trifluoromethyl)phenyl Sulfones for the Highly Stereoselective Julia–Kocienski Synthesis of α,β‐Unsaturated Esters and Weinreb Amides

et al. 2008

View full text Add to dashboard Cite

show abstract

“…This was achieved through ring opening of the lactone in 4 under basic conditions using aqueous KOHintert-butanol to afford ahydroxy acid, which was selectively oxidized using aqueous sodium ruthenate [18] to afford hemiacetal 10.T his was difficult to isolate cleanly,and in practice was trapped without delay using dimethyl(diazomethyl)phosphonate in methanol in the presence of potassium carbonate to install the requisite C-14 alkyne.T his carboxylic acid intermediate was also challenging to isolate effectively and hence we employed 4-(4,6-dimethoxy-1,3,5triazin-2-yl)-4-methylmorpholinium chloride to generate an activated ester in situ that was intercepted by N,O-dimethylhydroxylamine in the presence of N-methylmorpholine to afford Weinreb amide 11 in 73 %y ield over two steps from 4. [19] Addition of vinylmagnesium bromide in THF at 0 8 8C proceeded smoothly to afford ketone 3 in 87 %y ield. This heavily functionalized benzofuran is the key intermediate for our cascade approach to the morphine skeleton.…”

mentioning

confidence: 99%

A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine

et al. 2016

View full text Add to dashboard Cite

Morphine has been at arget for synthetic chemists since Robinson proposed its correct structure in 1925, resulting in al arge number of total syntheses of morphine alkaloids. Here we report atotal synthesis of (AE)-morphine that employs two key strategic cyclizations:1 )ad iastereoselective lightmediated cyclization of an O-arylated butyrolactone to form atricyclic cis-fused benzofuran and 2) acascade ene-yne-ene ring closing metathesis to forge the tetracyclic morphine core. This approach enables as hort and stereoselective synthesis of morphine in an overall yield of 6.6 %.Morphine (1), named by Sertürner for its tendency to induce sleep,isthe most abundant alkaloid isolated from the opium poppy Papaver somniferum.[1] As the main constituent of opium, morphinesp ain relieving properties have been exploited for thousands of years,a nd in modern times have resulted in its place on the World Health Organizationslist of essential medicines.[2] Its correct structure was proposed by Robinson in 1925, [3] and was confirmed by Gates (through total synthesis,1 952) [4] and Hodgkin (using X-ray crystallography,1955).[5] Currently,all medicinal (and illicit) morphine is derived from natural sources;t here is no synthetic route that competes on scale and cost with isolation from natural sources.This problem has been elegantly outlined in arecent perspective from Hudlicky,w hich focuses on his groups chemoenzymatic approaches to the morphine skeleton, [6] and in other reviews which focus on the range of strategies employed in total syntheses of morphine alkaloids.[7] Nonetheless,t he combination of potent biological effects and ac omplex pentacyclic structure bearing five contiguous stereocentres has made morphine and its associated alkaloids an enduring challenge for synthetic chemistry,r esulting in more than 30 total or formal syntheses of morphine alkaloids. [8,9] Our proposed strategy for the total synthesis of morphine is outlined below (Scheme 1). It has been demonstrated by Fuchs that the piperidine ring in morphine (1)can be made by an intramolecular 1,6-addition of an amine analogous to that in 2.[10] This requires an a,b,g,d-unsaturated ketone,which we envisaged could be constructed via acascade ene-yne-ene ring closing metathesis from the heavily functionalized benzofuran 3. [11,12] Ametathesis cascade cyclization offers the potential for anew end-game to the total synthesis of morphine in which the requisite functional groups are installed prior to the formation of the Band Crings.This has the advantage of minimizing late-stage functional group interconversions once the ABCD tetracycle is complete. Theb enzofuran 3 could be synthesized from the tricyclic butyrolactone 4 by as eries of functional group interconversions to install the vinyl ketone and alkyne functional groups. We recognized that the cis-fused butyrolactone 4,bearing an all-carbon quaternary stereocentre,c ould be generated via ap hotocyclization from substituted butenolide 5,w ith the relative stereochemistry ac onsequence of the 5,5-c...

show abstract

“…The latter was purchased from Aldrich. The known products 7a ,17a 7b ,17b 7c ,17c 7d ,17d 7e ,17d and 7k 15 gave satisfactory analytical and spectroscopic data.…”

Section: Methodsmentioning

confidence: 82%

New Reagent for Convenient Access to the α,β‐UnsaturatedN‐Methoxy‐N‐methyl‐amide Functionality by a Synthesis Based on the Julia Olefination Protocol

Manjunath¹,

Sane²,

Aidhen³

2006

Eur J Org Chem

View full text Add to dashboard Cite

A new reagent for the synthesis of the α,β-unsaturated Nmethoxy-N-methyl-amide structural unit has been developed. 2-(Benzo [d]thiazol-2-ylsulfonyl)-N-methoxy-N-methylacetamide, a crystalline solid with an indefinite shelf life that can be easily prepared in two convenient steps from 2-In contrast to the α,β-unsaturated ester structural unit which boasts a rich chemistry and has often been a common target in organic synthesis, the interest in the α,β-unsaturated N-methoxy-N-methyl-amide structural unit has found a significant surge only in recent times. This unit has served as a valuable functionality in many synthetic endeavours [1] because of the presence of a versatile N-methoxy-N-methyl-amide functionality, popularly known as Weinreb amide (WA).[2] WA has been an excellent carbonyl equivalent with large applications in organic synthesis exclusively because of its ease of preparation and its versatile reactivity, for example, in nucleophilic addition and selective reduction reactions to form aldehydes.[3] Among the many applications of the α,β-unsaturated N-methoxy-N-methylamide functionality, this structural unit has shown unique distinction on two occasions. In the light of the fact that α,β-unsaturated aldehydes and ketones have been poor substrates for the asymmetric dihydroxylation (AD) process, the facile and convenient AD process at the α,β-unsaturated Weinreb amide has brought to the surface their importance for indirect access to these functionalities.[4] A similar advantage has been observed during cyclopropanation of α,β-unsaturated N-methoxy-N-methyl-amide for indirect access to α,β-cyclopropyl ketones, particularly when well-documented direct cyclopropanation of α,β-unsaturated ketones failed. Currently, two approaches are available in the literature to obtain the α,β-unsaturated N-methoxy-N-methyl-amide structural unit. The first approach, based on Wittig carbonyl olefination, uses N-methoxy-N-methyl-2-(triphenylphosphoranylidene)acetamide [6] or its Horner-WadsworthEmmons (HWE) variant, [7] whereas the second approach makes use of N-methoxy-N-methyl-2-(phenylsulfinyl)acetamide [8] as a reagent for reaction with alkyl halides to furnish the same target. Although the former approach shows significant potential for general use, the latter has been severely restricted to nonfunctionalized and simple substrates. None of the approaches have been used to extend the chain on aldehydes from the carbohydrate domain. Our own Figure 1. Reaction of reagent 2 with various aldehydes to give α,β-unsaturated Weinreb amides.

show abstract

Preparation of Weinreb Amides Using 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium Chloride (DMT-MM)

Cited by 22 publications

References 18 publications

3,5‐Bis(trifluoromethyl)phenyl Sulfones for the Highly Stereoselective Julia–Kocienski Synthesis of α,β‐Unsaturated Esters and Weinreb Amides

3,5‐Bis(trifluoromethyl)phenyl Sulfones for the Highly Stereoselective Julia–Kocienski Synthesis of α,β‐Unsaturated Esters and Weinreb Amides

A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine

New Reagent for Convenient Access to the α,β‐UnsaturatedN‐Methoxy‐N‐methyl‐amide Functionality by a Synthesis Based on the Julia Olefination Protocol

Contact Info

Product

Resources

About