Tosylhydrazones and alkyllithium reagents: More on the regiospecificity of the reaction and the trapping of three intermediates

Shapiro, Robert H.; Lipton, M. F.; Kolonko, K. J.; Buswell, R.L.; Capuano, Lilly

doi:10.1016/s0040-4039(00)75263-4

Cited by 86 publications

(35 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both the 1 H and 13 C NMR spectra indicated the presence of a single product, providing evidence that the double bond had formed regiospecifically. From the literature data, [32] this result was predictable and may arise from the syn-dianion effect. Several studies have shown that in ether solvents the geometry of the tosylhydrazone directs the regioselectivity of alkene formation.…”

Section: Synthesis Of Aminonitrile 15mentioning

confidence: 71%

Total Synthesis of (±)‐Pumiliotoxin C: An Electrochemical Approach

et al. 2005

View full text Add to dashboard Cite

The total stereoselective synthesis of the decahydroquinoline alkaloid (±)‐pumiliotoxin C (cis‐195A, 1) is described. The compound was prepared in 15 steps from the commercially available 4‐piperidone ethylene ketal 2, in an overall 5 % yield. New C–C bonds in the α position relative to the nitrogen atom were formed by the metalation of aminonitriles 4 and 15, which were themselves prepared electrochemically. The ease of this synthesis shows that the N‐aryl group is an efficient nitrogen‐protecting group that can be removed in the last step through a Birch dearomatization. In addition, the aryl substituent serves as an efficient activator of the nitrogen atom during the elaboration of aminonitriles 4 and 15. The oxygen atom of the keto carbonyl group in octahydroquinolinone 10 was removed by an unprecedented two‐step method involving a Shapiro reaction and a palladium‐catalyzed reduction of the intermediate alkene 13. Finally, the expected stereospecific alkylation–hydride reduction process of the cis‐fused aminonitrile 15 established the trans relationship between the propyl group at C‐2 and the methyl substituent at C‐5. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

show abstract

Section: Synthesis Of Aminonitrile 15mentioning

confidence: 71%

Total Synthesis of (±)‐Pumiliotoxin C: An Electrochemical Approach

et al. 2005

View full text Add to dashboard Cite

show abstract

Section: )mentioning

confidence: 99%

“…[21][22][23] To the best of our knowledge, this selective epoxide rearrangement has never been reported earlier for bicyclo[2,2,2]heterocycles containing epoxides. [24][25][26][27][28][29] While three type of products could be obtained, allyl alcohols, aldehyde and saturated alcohols, arising most likely by carbenoid insertion processes, 24-26) the transformation was highly selective and afforded the desired crucial allyl alcohol 6 exclusively, in 96% of isolated yield (see Experimental).Alternatively, we have also discovered that 6 could be efficiently generated via the Shapiro reaction, [30][31][32] by the known trisylhydrazone 7 with excess n-BuLi followed by quenching the nucleophilic vinyllithium reagent with paraformaldehyde.33) After acetylation of the alcohol 6 under standard conditions affording the allylic acetate 8, 34) the critical allylic alkylation step was studied and optimized. Palladium-catalyzed allylic amination is a well-established method for the synthesis of allyl amines.…”

mentioning

confidence: 99%

“…Alternatively, we have also discovered that 6 could be efficiently generated via the Shapiro reaction, [30][31][32] by the known trisylhydrazone 7 with excess n-BuLi followed by quenching the nucleophilic vinyllithium reagent with paraformaldehyde. 33) After acetylation of the alcohol 6 under standard conditions affording the allylic acetate 8, 34) the critical allylic alkylation step was studied and optimized.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Expedient Synthesis of Mequitazine an Antihistaminic Drug by Palladium Catalyzed Allylic Alkylation of Sodium Phenothiazinate

Gonnot

Nicolas

Mioskowski

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

The synthesis of therapeutically important drugs remains a major focus of attention among organic chemists in the academic world as well as in pharmaceutical companies. Particularly appealing is the notion of using green, short and scalable mild processes that rely on atom economy transformations.2-4) Importantly, a large number of synthetic bioactive molecules possess the 3-substituted quinuclidine moiety that exhibits a broad pharmacological profile (Fig. 1). [5][6][7][8][9][10] Mequitazine 1, is a potent H 1 -receptors selective antihistaminic drug widely studied and used for allergic disorders such as hay fever and urticaria. This molecule is also one of the earliest second-generation antihistamines on the market, sold as the trade name Primalan ® , which is beneficial in the symptomatic treatment of allergic rhinitis.11) Recent studies have demonstrated its potential use for the treatment of allergic conjunctivitis, and for its possible sedative properties. 12)As a consequence the development of efficient synthesis of 1 is of prime importance for clinical evaluations, and more importantly for the elucidation of the mechanism of action with different biological targets and receptors. The existing strategies for the preparation of mequitazine 1, most of which have been patented, rely mainly on the construction of the C9-N bond, either by alkylation or acylation of phenothiazine using appropriate 3-substituted quinuclidine electrophiles. [13][14][15][16][17][18] However, these approaches are plagued by severe drawbacks such as, the rapid formation of large amount of the elimination product arising from 3-halomethyl-quinuclidine electrophiles, or the degradation of the sensitive 3-acyl-quinuclidine halide derivative. As part of our ongoing program on medicinal chemistry, 16) we wish to describe a new strategic approach that circumvents these limitations in developing a reliable synthetic route for an expedient synthesis of racmequitazine. The key step of our approach is based on the palladium catalyzed allylic alkylation of sodium phenothiazinate. As shown in Chart 1, we first started with the preparation of the key allyl acetate 8. The treatment of the known epoxide 19,20) 5 with lithium diethylamide in ether under reflux conditions, resulted in a remarkably clean conversion to the corresponding allyl alcohol 6. [21][22][23] To the best of our knowledge, this selective epoxide rearrangement has never been reported earlier for bicyclo[2,2,2]heterocycles containing epoxides. [24][25][26][27][28][29] While three type of products could be obtained, allyl alcohols, aldehyde and saturated alcohols, arising most likely by carbenoid insertion processes, 24-26) the transformation was highly selective and afforded the desired crucial allyl alcohol 6 exclusively, in 96% of isolated yield (see Experimental).Alternatively, we have also discovered that 6 could be efficiently generated via the Shapiro reaction, [30][31][32] by the known trisylhydrazone 7 with excess n-BuLi followed by quenching the nucleophilic vinyllithium ...

show abstract

“…730s, 690s. - (25), 175 (8), 149 (14), 135 (26), 123 (38). 109 (36), 95 (25), 77 (38), 41 (21), 28 (23).…”

Section: )mentioning

confidence: 99%

Synthese von Carotinoiden mit hydroxylierter Methylgruppe an der Polyenkette mit Hilfe von Vinyl‐Anionen (Shapiro‐Reaktion)

Bütikofer

Eugster

1983

Helvetica Chimica Acta

View full text Add to dashboard Cite

Syntheses of Hydroxymethyl‐carotenoids Using Vinyl‐Anions Generated by the Shapiro‐Reaction A versatile synthesis of hydroxymethyl‐carotenoids with β‐ or ϵ‐end groups is presented. It makes use of the reactive vinyl anions prepared by the Shapiro‐reaction from (phenylsulfonyl)hydrazones of polyenones and their smooth 1,2‐addition to polyenals. Thus, e.g. (3R,6′R)‐β, ϵ‐carotene‐3, 19‐diol (72), an optically active model compound structurally very close to loroxanthin (1), has been synthesized.

show abstract

Tosylhydrazones and alkyllithium reagents: More on the regiospecificity of the reaction and the trapping of three intermediates

Cited by 86 publications

References 5 publications

Total Synthesis of (±)‐Pumiliotoxin C: An Electrochemical Approach

Total Synthesis of (±)‐Pumiliotoxin C: An Electrochemical Approach

Expedient Synthesis of Mequitazine an Antihistaminic Drug by Palladium Catalyzed Allylic Alkylation of Sodium Phenothiazinate

Synthese von Carotinoiden mit hydroxylierter Methylgruppe an der Polyenkette mit Hilfe von Vinyl‐Anionen (Shapiro‐Reaktion)

Contact Info

Product

Resources

About