Intramolecular Schmidt Reaction Research Articles

Domino Reactions that Combine an Azido‐Schmidt Ring Expansion with the Diels—Alder Reaction.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Domino Reactions That Combine an Azido-Schmidt Ring Expansion with the Diels−Alder Reaction

[reaction: see text] The combination of the intramolecular Schmidt reaction with the Diels-Alder reaction provides expedient access to a variety of heterocycles. Two different modes of reaction planning are presented. In one, the azide and ketone moieties necessary for the intramolecular Schmidt reaction originate on different molecules that are reacted and subsequently undergo a ring-adjustment step. Alternatively, an azido ketone can be used provided the ketone is deactivated by its presence in an enone.

Asymmetric total synthesis of dendrobatid alkaloids: preparation of indolizidine 251F and its 3-desmethyl analogue using an intramolecular Schmidt reaction strategy.

Total syntheses of alkaloid 251F (1), a natural product detected from the skin extracts of the dendrobatid frog species Minyobates bombetes, and its racemic 3-desmethyl derivative (2) are reported. A Diels-Alder reaction initiated both syntheses and established four consecutive stereogenic centers. Important to the synthesis of 2 was a first-generation ozonolysis/olefination/aldol strategy to convert a [2.2.1] bicyclic acid to the [3.3.0]bicyclooctane diquinane 4b. Further elaboration to an appropriate keto azide allowed for a key intramolecular Schmidt reaction to deliver the tricyclic core of the target molecule. In a second-generation approach, a tandem ring-opening/ring-closing metathesis reaction effected an overall [2.2.1] --> [3.3.0] skeletal rearrangement to deliver diquinane 4a. In similar fashion, 4a was manipulated to an appropriate keto azide, and an intramolecular Schmidt reaction generated the core cyclic architecture of 251F.

Asymmetric Total Synthesis of Dendrobatid Alkaloid 251F.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A combined intramolecular Diels-Alder/intramolecular schmidt reaction: formal synthesis of (+/-)-stenine.

Four stereocenters and three rings are established in one step in a new formal synthesis of (±)-stenine (see scheme). This key reaction cascade consists of an intramolecular Diels–Alder reaction followed by an intramolecular Schmidt reaction. The resulting tricyclic intermediate was readily transformed into a known intermediate en route to stenine, thus completing the formal synthesis.

Asymmetric total synthesis of dendrobatid alkaloid 251F.

The dendrobatid alkaloid (-)-251F was synthesized. The key steps of the synthesis were (1) an asymmetric Diels-Alder reaction to establish four of the necessary stereocenters in the target, (2) a ring-opening/ring-closing metathesis reaction to establish a key [3.3.0] bicyclic intermediate, and (3) an intramolecular Schmidt reaction.

First Asymmetric Total Synthesis of (+)-Sparteine

[reaction: see text] The total synthesis of (+)-sparteine was accomplished from 2,5-norbornadione in 15 steps and 15.7% overall yield. The key steps were two ring-expansion reactions, one involving an intramolecular Schmidt reaction and one using a novel variant of the photo-Beckmann rearrangement.

A Schmidt route to 1-azabicyclo[x.y.0]alkanes: a comparison of carbocation stabilizing groups

Abstract The intramolecular Schmidt reactions of tertiary alkyl, tertiary benzylic, tertiary propargylic, and tertiary allylic carbocations with tethered azides are reported. Using product analysis and deuterium labeling studies, the role of cation rearrangement prior to Schmidt reaction is reported.

Intramolecular reactions of benzylic azides with ketones: competition between Schmidt and Mannich pathways.

The Lewis acid-promoted reactions of benzylic azides with ketones can proceed by two major pathways. The azido-Schmidt reaction involves simple addition of azide to the ketone followed by rearrangement and ring expansion. In addition, benzylic azides can undergo prior rearrangement to afford iminium ions that can subsequently participate in a Mannich reaction. A series of ketones containing an alpha CH2(CH2)nCH(N3)Ph substituent (n = 1-3) was prepared to investigate the dependence of products on ketone ring size and tether length. For all ketones examined, good yields of bicyclic lactams arising from intramolecular Schmidt reaction were obtained when a four-carbon linker was used (n = 1 in the above formulation), but Mannich products predominated for the longer tethers examined (n = 2, 3).

Azidomercurations of alkenes: mercury-promoted Schmidt reactions.

Azides bearing a suitably disposed alkene, when treated with either mercuric perchlorate or mercuric trifluoromethanesulfonate, produce bicyclic iminium ions. This new version of the Schmidt reaction proceeds by capture of the mercuronium ion intermediate by the azide to produce an aminodiazonium ion, which suffers a 1,2-shift to give an iminium ion (e.g., 10 --> 16 --> 17 --> 18). Reduction of the iminium ion may then be carried out to produce an amine. Compared to earlier work on the protic acid-promoted intramolecular Schmidt reaction of azido-alkenes, the mercury-promoted Schmidt reaction has several advantages. First, the acid-promoted Schmidt reaction of azido-alkenes requires that the intermediate carbocations be tertiary, allylic, benzylic, or propargylic. The mercury-promoted method has no such limitation; thus even 1,2-disubstituted alkenes may be used. Second, the mercury-promoted method is milder, allowing the presence of acid-sensitive functionality. The protic version, typically employing trifluoromethanesulfonic acid, is limited in its functional group tolerance. Third, whereas carbocation rearrangement is often observed prior to cyclization/rearrangement in the acid-promoted Schmidt reaction, the mercury-promoted method avoids this problem. Fourth, the presence of the mercurio group during the rearrangment may alter the regioselectivity of the 1,2-migration. Finally, the mercury-bearing iminium ions that are the result of the Schmidt reaction were found to be sensitive to protodemercuration, precluding their use in other transformations.

ChemInform Abstract: Regiocontrol in an Intramolecular Schmidt Reaction: Total Synthesis of (+)-Aspidospermidine.

A total synthesis of (+)-aspidospermidine (1) is described, featuring an intramolecular Schmidt reaction as the key step. The effects of stereochemistry and protecting group status on the regio- an...

Regiocontrol in an intramolecular Schmidt reaction: total synthesis of (+)-aspidospermidine.

[reaction--see text] A total synthesis of (+)-aspidospermidine (1) is described, featuring an intramolecular Schmidt reaction as the key step. The effects of stereochemistry and protecting group status on the regio- and chemoselectivity of this reaction were examined.

ChemInform Abstract: The Intramolecular Schmidt Reaction of Azides with Tertiary Alkohols: Synthesis of 5‐(α‐Naphthyl)‐ and 5‐(β‐Naphthyl) indolizidines as Potential Dopamine Analogues and Non‐Opiate Antinociceptive Agents.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The intramolecular Schmidt reaction of azides with tertiary alcohols: Synthesis of 5-(α-naphthyl)- and 5-(β-naphthyl)indolizidines as potential dopamine analogs and non-opiate antinociceptive agents

Intramolecular Schmidt reaction of the azido alcohols 9, 11, and 12 afforded the 5-naphthylindolizidines 10, 13, and 14, respectively. The naphthylmethylamine subunit present in each has an amine and a π-system oriented in a fashion similar to the β-phenethylamine subunit of dopamine and many of its agonists and antagonists. These analogs also closely resemble the bicyclic tertiary amines 8, which have recently been found to exhibit non-opiate analgesic activity. Testing of 10, 13, and 14 for dopaminergic activity is described.

Toward the synthesis of sparteine: Intramolecular Schmidt reactions on a norbornanone platform

The intramolecular Schmidt reaction was applied to the norbornane skeleton to examine an approach to sparteine. In so doing, the stereospecificity of intramolecular Schmidt reactions of ε-azido ketones was demonstrated. The intramolecular Schmidt reaction was found to fail in a ketone containing a lactam moiety.

Intramolecular Schmidt reactions of alkyl azides with ketals and enol ethers

The ketals or enol ethers of 1,5-azidoketones were converted into lactams using a two-stage process. Treatment of the ketals and enol ethers with acid (trifluoroacetic acid, triflic acid, or trimethylsilyl triflate) afforded an oxonium ion which reacted with the tethered azide to give a 1,1-azido-alkoxy intermediate. Bond reorganization led to an iminium ether that was reacted with sodium iodide in acetone to expose the amide products. Seven intramolecular examples proceeding in yields of 68 to ≥95% are reported using dimethyl or diethyl ketals. Attempts using 1,3-dioxolanes and an intermolecular example are also described.

Preparation of 2-Substituted Pyrrolines by an Intramolecular Schmidt Reaction of 4-Substituted 3-Butenyl Azides

Preparation of 2-Substituted Pyrrolines by an Intramolecular Schmidt Reaction of 4-Substituted 3-Butenyl Azides

ChemInform Abstract: Intramolecular Schmidt Reactions of Azides with Carbocations: Synthesis of Bridged‐Bicyclic and Fused‐Bicyclic Tertiary Amines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Application of the Intramolecular Schmidt Reaction to the Asymmetric Synthesis of (‐)‐Indolizidine 209B from Pulegone.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Intramolecular Schmidt reactions of azides with carbocations: synthesis of bridged-bicyclic and fused-bicyclic tertiary amines

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntramolecular Schmidt reactions of azides with carbocations: synthesis of bridged-bicyclic and fused-bicyclic tertiary aminesWilliam H. Pearson, Rajesh Walavalkar, Jeffrey M. Schkeryantz, Wen Kui Fang, and James D. BlickensdorfCite this: J. Am. Chem. Soc. 1993, 115, 22, 10183–10194Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://doi.org/10.1021/ja00075a038RIGHTS & PERMISSIONSArticle Views1213Altmetric-Citations86LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (2 MB) Get e-Alerts Get e-Alerts