N-Sulfinyl imine

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Sulfinimine Sulfinimine.png
Sulfinimine

N-Sulfinyl imines (N-sulfinylimines, sulfinimines, thiooxime S-oxides) are a class of imines bearing a sulfinyl group attached to nitrogen. [1] [2] [3] [4] [5] [6] [7] [8] These imines display usefully stereoselectivity reactivity and due to the presence of the chiral electron withdrawing N-sulfinyl group. They allow 1,2-addition of organometallic reagents to imines. The N-sulfinyl group exerts powerful and predictable stereodirecting effects resulting in high levels of asymmetric induction. Racemization of the newly created carbon-nitrogen stereo center is prevented because anions are stabilized at nitrogen (i.e., the sulfinyl group is a versatile amine protection group). The sulfinyl chiral auxiliary is readily removed by simple acid hydrolysis. The addition of organometallic reagents to N-sulfinyl imines is the most reliable and versatile method for the asymmetric synthesis of amine derivatives. These building blocks have been employed in the asymmetric synthesis of numerous biologically active compounds. [1] [2] [3] [4] [5] [6] [7] [8]

Contents

Synthesis

The first N-sulfinyl imines in racemic form were formed by oxidation of p-toluene-sulfenyl imines with m-CPBA. [9] Enantiopure p-toluene-sulfinyl imines arise by the reaction of the commercially available Andersen reagent (menthyl p-toluenesulfinate) [10] with metallo-ketimines but is limited to ketone derived N-sulfinyl imines. [11] A more general method for the preparation of N-sulfinyl imines is the asymmetric oxidation of achiral sulfenyl imines with a chiral oxaziridine. [12] The utility of this method is limited by the availability of the N-sulfonyloxaziridine, which is difficult to prepare. [13] More practical is the one-pot procedure from the Andersen reagent making a variety of p-toluene-sulfinyl imines available from both aromatic and aliphatic aldehydes. [14]

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A widely used method for the asymmetric synthesis of N-sulfinyl imines is the condensation of enantiopure primary sulfinamides with aldehyde or ketones. [1] [2] [3] [4] [5] [6] [7] A mild Lewis acid dehydrating reagents such as titanium ethoxide facilitate the condensation. [15] [16] Many sulfinamides are commercially available in both (R)- and (S)-forms. The two most commonly used are the Davis p-toluene-sulfinamide and the Ellman tert-butanesulfinamide [8] [15] [16]

Chiral Imine Synthesis.png

Applications

Structure of 4-ClC6H4CH=NS(O)Bu-t. Selected distances: dS=O = 147.5, dN=C = 127.5, dS-N = 170.4 pm. Color scheme: red = O, blue = N, green = Cl, gray = C, white = H, yellow = S. ClC6H4CH=NS(O)Bu-t (WICPOP).png
Structure of 4-ClC6H4CH=NS(O)Bu-t. Selected distances: dS=O = 147.5, dN=C = 127.5, dS-N = 170.4 pm. Color scheme: red = O, blue = N, green = Cl, gray = C, white = H, yellow = S.

The p-toluene-sulfinyl imines have been used for the highly diastereoselective asymmetric synthesis of α-amino acids, [18] [19] β-amino acids, [20] [21] syn- and anti-2,3-diamino esters, [22] α-amino aldehydes and ketones, [23] [24] β-amino ketones, [25] [26] α-amino phosphonates, [27] [28] aziridine 2-carboxylates, [29] [30] and aziridine 2-phosphonates. [31] Many of these same transformations can be carried out with tert-butylsulfinyl imines. [8] For the asymmetric synthesis of amines, tert-butylsulfinyl imines are required as lithium and Grignard reagents react at the sulfinyl sulfur in p-toluene-sulfinyl imines. [8] Mild acid treatment readily removes the N-sulfinyl group in the sulfinamide products affording the free amine derivatives. An advantage of tert-butylsulfinyl imines is that acid treatment of the corresponding sulfinamides leads to easily removal by-products [8]

Sulfinimine Applications.png

Related Research Articles

Enamine

An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine. Enamines are versatile intermediates.

Imine Chemical compound

An imine is a functional group or organic compound containing a carbon–nitrogen double bond. The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bonds. Imines are common in synthetic and naturally occurring compounds and they participate in many reactions.

The Mannich reaction is a three-component organic reaction that involves the amino alkylation of an acidic proton next to a carbonyl functional group by formaldehyde and a primary or secondary amine or ammonia. The final product is a β-amino-carbonyl compound also known as a Mannich base. Reactions between aldimines and α-methylene carbonyls are also considered Mannich reactions because these imines form between amines and aldehydes. The reaction is named after Carl Mannich.

The Pictet–Spengler reaction is a chemical reaction in which a β-arylethylamine undergoes condensation with an aldehyde or ketone followed by ring closure. The reaction was first discovered in 1911 by Amé Pictet and Theodor Spengler. Traditionally an acidic catalyst in protic solvent was employed with heating, however the reaction has been shown to work in aprotic media in superior yields and sometimes without acid catalysis. The Pictet–Spengler reaction can be considered a special case of the Mannich reaction, which follows a similar reaction pathway. The driving force for this reaction is the electrophilicity of the iminium ion generated from the condensation of the aldehyde and amine under acid conditions. This explains the need for an acid catalyst in most cases, as the imine is not electrophilic enough for ring closure but the iminium ion is capable of undergoing the reaction.

The Reformatsky reaction is an organic reaction which condenses aldehydes or ketones with α-halo esters using metallic zinc to form β-hydroxy-esters:

Chiral auxiliary

A chiral auxiliary is a stereogenic group or unit that is temporarily incorporated into an organic compound in order to control the stereochemical outcome of the synthesis. The chirality present in the auxiliary can bias the stereoselectivity of one or more subsequent reactions. The auxiliary can then be typically recovered for future use.

In organic chemistry, the Arndt–Eistert reaction is the conversion of a carboxylic acid to its homologue. Named for the German chemists Fritz Arndt (1885–1969) and Bernd Eistert (1902–1978), the method entails treating an acid chlorides with diazomethane. It is a popular method of producing β-amino acids from α-amino acids.

The Strecker amino acid synthesis, also known simply as the Strecker synthesis, is a method for the synthesis of amino acids by the reaction of an aldehyde with ammonia in the presence of potassium cyanide. The condensation reaction yields an α-aminonitrile, which is subsequently hydrolyzed to give the desired amino acid. The method is used commercially for the production of racemic methionine from methional.

Weinreb ketone synthesis Chemical reaction

The Weinreb–Nahm ketone synthesis is a chemical reaction used in organic chemistry to make carbon–carbon bonds. It was discovered in 1981 by Steven M. Weinreb and Steven Nahm as a method to synthesize ketones. The original reaction involved two subsequent nucleophilic acyl substitutions: the conversion of an acid chloride with N,O-Dimethylhydroxylamine, to form a Weinreb–Nahm amide, and subsequent treatment of this species with an organometallic reagent such as a Grignard reagent or organolithium reagent. Nahm and Weinreb also reported the synthesis of aldehydes by reduction of the amide with an excess of lithium aluminum hydride.

In organophosphorus chemistry, the Kabachnik–Fields reaction is a three-component organic reaction forming α-aminomethylphosphonates from an amine, a carbonyl compound, and a dialkyl phosphonate, (RO)2P(O)H (that are also called dialkylphosphites). Aminophosphonates are synthetic targets of some importance as phosphorus analogues of α-amino acids (a bioisostere). This multicomponent reaction was independently discovered by Martin Izrailevich Kabachnik and Ellis K. Fields in 1952. The reaction is very similar to the two-component Pudovik reaction, which involves condensation of the phosphite and a preformed imine.

The Abramov reaction is the related conversions of trialkyl to α-hydroxy phosphonates by the addition to carbonyl compounds. In terms of mechanism, the reaction involves attack of the nucleophilic phosphorus atom on the carbonyl carbon. It was named after the Russian chemist Vasilii Semenovich Abramov (1904–1968) in 1957.

Electrophilic amination is a chemical process involving the formation of a carbon–nitrogen bond through the reaction of a nucleophilic carbanion with an electrophilic source of nitrogen.

<i>tert</i>-Butanesulfinamide Chemical compound

tert-Butanesulfinamide is an organosulfur compound and a member of the class of sulfinamides. Both enantiomeric forms are commercially available and are used in asymmetric synthesis as chiral auxiliaries, often as chiral ammonia equivalents for the synthesis of amines. tert-Butanesulfinamide and the associated synthetic methodology was introduced in 1997 by Jonathan A. Ellman et al.

Sulfinamide

Sulfinamide is a functional group in organosulfur chemistry with the structural formula RS(O)NR'2. This functionality is composed of a sulfur-carbon (S-C) and sulfur-nitrogen (S-N) single bonds, as well as a sulfur-oxygen double bond (S=O), resulting in a tetravalent sulfur centre. As a non-bonding electron pair is also present on the sulfur, these compounds are also chiral. They are sometimes referred to as S-chiral sulfinamides. Sulfinamides are amides of sulfinic acid.

Oxaziridine Chemical compound

An oxaziridine is an organic molecule that features a three-membered heterocycle containing oxygen, nitrogen, and carbon. In their largest application, oxaziridines are intermediates in the industrial production of hydrazine. Oxaziridine derivatives are also used as specialized reagents in organic chemistry for a variety of oxidations, including alpha hydroxylation of enolates, epoxidation and aziridination of olefins, and other heteroatom transfer reactions. Oxaziridines also serve as precursors to amides and participate in [3+2] cycloadditions with various heterocumulenes to form substituted five-membered heterocycles. Chiral oxaziridine derivatives effect asymmetric oxygen transfer to prochiral enolates as well as other substrates. Some oxaziridines also have the property of a high barrier to inversion of the nitrogen, allowing for the possibility of chirality at the nitrogen center.

Enders SAMP/RAMP hydrazone-alkylation reaction

The Enders SAMP/RAMP hydrazone alkylation reaction is an asymmetric carbon-carbon bond formation reaction facilitated by pyrrolidine chiral auxiliaries. It was pioneered by E. J. Corey and D. Enders in 1976, and was further developed by D. Enders and his group. This method is usually a three-step sequence. The first step is to form the hydrazone between (S)-1-amino-2-methoxymethylpyrrolidine (SAMP) or (R)-1-amino-2-methoxymethylpyrrolidine (RAMP) and a ketone or aldehyde. Afterwards, the hydrazone is deprotonated by lithium diisopropylamide (LDA) to form an azaenolate, which reacts with alkyl halides or other suitable electrophiles to give alkylated hydrazone species with the simultaneous generation of a new chiral center. Finally, the alkylated ketone or aldehyde can be regenerated by ozonolysis or hydrolysis.

Franklin Arnold Davis is the Laura H. Carnell Professor of Chemistry at Temple University in Philadelphia, Pennsylvania. He is most notable for his development of sulfur-nitrogen reagents including N-sulfonyloxaziridine for oxidations and asymmetric hydroxylations and N-sulfinyl imines for the asymmetric synthesis of chiral amine derivatives. The reagents are commonly called Davis oxaziridines and Davis sulfinamides, respectively. Davis oxidation and Davis' reagent are both named after him.

In organic chemistry, the Davis oxidation or Davis' oxaziridine oxidation refers to oxidations involving the use of the Davis reagent or other similar oxaziridine reagents. This reaction mainly refers to the generation of α-hydroxy carbonyl compounds (acyloins) from ketones or esters. The reaction is carried out in a basic environment to generate the corresponding enolate from the ketone or ester. This reaction has been shown to work for amides.

The De Kimpe azirdine synthesis is a name reaction of organic chemistry, for the generation of aziridines by the reaction of α-chloroimines with nucleophiles such as hydride, cyanide, or Grignard reagents.

The ketimine Mannich reaction is an asymmetric synthetic technique using differences in starting material to push a Mannich reaction to create an enantiomeric product with steric and electronic effects, through the creation of a ketimine group. Typically, this is done with a reaction with proline or another nitrogen-containing heterocycle, which control chirality with that of the catalyst. This has been theorized to be caused by the restriction of undesired (E)-isomer by preventing the ketone from accessing non-reactive tautomers. Generally, a Mannich reaction is the combination of an amine, a ketone with a β-acidic proton and aldehyde to create a condensed product in a β-addition to the ketone. This occurs through an attack on the ketone with a suitable catalytic-amine unto its electron-starved carbon, from which an imine is created. This then undergoes electrophilic addition with a compound containing an acidic proton. It is theoretically possible for either of the carbonyl-containing molecules to create diastereomers, but with the addition of catalysts which restrict addition as of the enamine creation, it is possible to extract a single product with limited purification steps and in some cases as reported by List et al.; practical one-pot syntheses are possible. The process of selecting a carbonyl-group gives the reaction a direct versus indirect distinction, wherein the latter case represents pre-formed products restricting the reaction's pathway and the other does not. Ketimines selects a reaction group, and circumvent a requirement for indirect pathways.

References

  1. 1 2 3 Davis, Franklin A; Zhou, Ping; Chen, Bang-Chi (1998). "Asymmetric synthesis of amino acids using sulfinimines (thiooxime S-oxides)". Chemical Society Reviews. 27: 13. doi:10.1039/A827013Z.
  2. 1 2 3 Davis, Franklin A; Zhou, Ping; Chen, Bang-Chi (2004). "Recent advances in asymmetric reactions using sulfinimines (N-sulfinyl imines)". Tetrahedron. 60 (37): 8003–8030. doi:10.1016/j.tet.2004.06.071.
  3. 1 2 3 Senanayake, Chris H; Krishnamurthy, Dhileepkumar; Luy, Zhi-Hui; Gallou, I (2005). "Enantiopure sulfoxides and sulfinamides: recent developments in their stereoselective synthesis and applications to asymmetric synthesis". Aldrichimica Acta. 38 (40): 93. doi:10.1002/chin.200640264.
  4. 1 2 3 Morton, Daniel; Stockman, Robert A (2006). "Chiral non-racemic sulfinimines: versatile reagents for asymmetric synthesis". Tetrahedron. 62 (38): 8869–8905. doi:10.1016/j.tet.2006.06.107.
  5. 1 2 3 Davis, Franklin A (2006). "Adventures in sulfur-nitrogen chemistry". Journal of Organic Chemistry. 71 (24): 8993–9003. doi:10.1021/jo061027p. PMID   17109522.
  6. 1 2 3 Edupuganti, Ramakrishna; Davis, Franklin A (2012). "Synthesis and Applications of Masked Oxo-Sulfinamides in Asymmetric Synthesis". Organic and Biomolecular Chemistry. 10 (26): 5021–31. doi:10.1039/c2ob25345c. PMID   22576951.
  7. 1 2 3 Davis, Franklin A; Friedman, Arthur J.; Kluger, Edward W (1974). "Chemistry of the sulfur-Nitrogen Bond. VIII. N-Alkylidenesulfinamides". Journal of the American Chemical Society. 96 (15): 5000–5001. doi:10.1021/ja00822a055.
  8. 1 2 3 4 5 6 Ellman, Jonathan; Robak, Maryann T.; Herbage, Melissa A. (2010). "Synthesis and applications of tert-Butanesulfinamide". Chemical Reviews. 110 (6): 3600–740. doi:10.1021/cr900382t. PMID   20420386.
  9. ↑ Hulce, Martin; Mallomo, John P.; Frye, Leah L.; Kogan, Timothy P.; Posner Gary H (1990). Organic Syntheses, Collected Volume. 7: 495.{{cite journal}}: Missing or empty |title= (help)
  10. ↑ Cinquini, Mauro; Cozzi, Franco (1977). "Synthesis of Optically active N-alkylidenesulphinamides". Journal of the Chemical Society, Chemical Communications (14): 502. doi:10.1039/c3977000502b.
  11. ↑ Davis, Franklin A.; Reddy, Thimma R.; Reddy, Rajaraathnam E. (1992). "Asymmetric Synthesis of Sulfinimines: Applications to the Synthesis of Nonracemic β-Amino acids and α-hydroxy-β-amino acids". Journal of Organic Chemistry. 57 (24): 6387–6389. doi:10.1021/jo00050a007.
  12. ↑ Davis, Franklin A; Reddy, Thimma R.; Han, Wei; Carroll, P. J (1992). "Chemistry of Oxaziridines. 17. N-(Phenylsulfonyl)(3,3-dichlorocamphoryl)oxaziridine: A Highly Efficient Reagent for the Asymmetric Oxidation of Sulfide to Sulfoxides". Journal of the American Chemical Society. 114 (4): 1428–1437. doi:10.1021/ja00030a045.
  13. ↑ Davis, Franklin A.; Reddy, Rajharathnam E.; Szewczyk, Joanna M.; Reddy, G. Venkat; Portonovo, Padma S.; Zhang, Huiming; Fanelli, Dean; Reddy, R. Thimma; Zhou, Ping; Carroll, Patrick J. (1997). "Asymmetric Synthesis and Properties of Sulfinimines (Thiooxime S-Oxides)". Journal of Organic Chemistry. 62 (8): 2555–2563. doi:10.1021/jo970077e. PMID   11671597.
  14. ↑ Liu, Guangcheng; Cogan, Derek. A.; Owens, Timothy D.; Tang, Tony P.; Ellman, Jonathan A. (1999). "Synthesis of Enantiomerically Pure N-tert-Butanesulfinyl Imines (tert-Butanesulfinimines) by the Direct Condensation of tert-Butanesulfinamide with aldehydes and ketones". Journal of Organic Chemistry. 64 (4): 1278–1284. doi:10.1021/jo982059i.
  15. 1 2 Davis, Franklin A.; Zhang Yulian; Andemichael, Yemane; Fang, Tianan; Fanelli, Dean L.; Zhang, Huiming (1999). "Improved Synthesis of Enantiopure Sulfinimines (Thiooxime S-Oxides) from p-Toluenesulfinamides and Aldehydes and Ketones". Journal of Organic Chemistry. 64 (4): 1403–1406. doi:10.1021/jo9820622.
  16. 1 2 Davis, Franklin A.; Portonovo, Padma S.; Reddy, Rajarathnam E.; Chiu, Yu-hung (1996). "Asymmetric Strecker Synthesis using Enantiopure Sulfinimines and Diethylaluminum Cyanide: The Alcohol Effect". Journal of Organic Chemistry. 61 (2): 440–441. doi:10.1021/jo9519928. PMID   11666956.
  17. ↑ Guo, Tao; Song, Ran; Yuan, Bin-Hua; Chen, Xiao-Yang; Sun, Xing-Wen; Lin, Guo-Qiang (2013). "Highly efficient asymmetric construction of quaternary carbon-containing homoallylic and homopropargylic amines". Chemical Communications. 49 (47): 5402–5404. doi:10.1039/C3CC42481B. PMID   23657470.
  18. ↑ Davis, Franklin A; Srirajan, Vaidyanathan; Titus, Donald D. (1999). "Efficient Asymmetric Synthesis of β-Fluoro α-Amino Acids". Journal of Organic Chemistry. 64 (18): 6931–6934. doi:10.1021/jo990947n. PMID   11674714.
  19. ↑ Davis, Franklin A; Reddy, Rajarathnam E.; Szewczyk, Joanna M. (1995). "Asymmetric Synthesis of (R)-(+)-β-Phenylalanine from (S)-(+)-Benzylidene-p-toluenesulfinamide. Regeneration of the Sulfinimine Precursor". Journal of Organic Chemistry. 60 (21): 7037–7039. doi:10.1021/jo00126a070.
  20. ↑ Davis, Franklin A; Szewczyk, Joanna M.; Reddy, Rajarathnam E (1996). "An Efficient Synthesis of (+)-(S)-Ethyl-β-Amino-3-pyridinepropanoate Using Enantiopure Sulfinimines". Journal of Organic Chemistry. 61 (6): 2222–2225. doi:10.1021/jo951917x.
  21. ↑ Davis, Franklin A; Zhang, Yanfeng; Qiu, Hui (2007). "Asymmetric Synthesis of anti- and syn-2,3-Diamino Esters using Sulfinimines. Water and Concentration Effects". Organic Letters. 9 (5): 833–836. doi:10.1021/ol063058c. PMC   2533706 . PMID   17261004.
  22. ↑ Davis, Franklin A.; Ramachandar, Tokala; Liu Hu (2004). "Asymmetric Synthesis of α-Amino 1,3-Dithioketals from Sulfinimines (N-Sulfinyl Imines). Synthesis of (2S,3R)-(-)-3-Hydroxy-3-methylproline". Organic Letters. 6 (19): 3393–5. doi:10.1021/ol0485971. PMID   15355060.
  23. ↑ Davis, Franklin A; Ramachandar, Tokala; Chai, Jing; Skucas, Eduardas (2006). "Asymmetric Synthesis of α-Amino Aldehydes from Sulfinimine (N-Sulfinyl Imine)-Derived α-Amino 1,3-Dithianes. Formal Synthesis of (-)-2,3-trans-3,4-cis-Dihydroxy Proline". Tetrahedron Letters. 47: 2743. doi:10.1016/j.tetlet.2006.02.092.
  24. ↑ Davis, Franklin A; Nolt, M. Brad; Wu, Yongzhong; Prasad, Kavirayani R.; Li, Danyang; Yang, Bin; Bowen, Kerisha; Lee, Seung H.; Eardley, John H. (2005). "Asymmetric Synthesis of β-Amino Carbonyl Compounds with N-Sulfinyl β-Amino Weinreb Amides". Journal of Organic Chemistry. 70 (6): 2184–2190. doi:10.1021/jo0402780. PMID   15760203.
  25. ↑ Davis, Franklin A; Song Minsoo (2007). "Asymmetric Synthesis of syn-α-Substituted β-Amino Ketones using Sulfinimines and Prochiral Weinreb Amide Enolates". Organic Letters. 9 (12): 2413–2416. doi:10.1021/ol0708166. PMID   17497798.
  26. ↑ Davis, Franklin A; Lee, Seung; Yan, Hongxing; Titus, Donald D. (2001). "Asymmetric Synthesis of Quaternary α-Amino Phosphonates using Sulfinimines". Organic Letters. 3 (11): 1757–1760. doi:10.1021/ol015945f. PMID   11405704.
  27. ↑ Davis, Franklin A.; Lee, Seung; Xu, He (2004). "Asymmetric Synthesis of Cyclic α-Amino Phosphonates using Masked Oxo Sulfinimines (N-Sulfinyl Imines)". Journal of Organic Chemistry. 69 (11): 3777. doi:10.1021/jo040127x. PMID   15153008.
  28. ↑ Davis, Franklin A.; Zhou, Ping; Reddy, G. Venkat (1994). "Asymmetric Synthesis and Reactions of cis-N-(p-Toluenesulfinyl)aziridine-2-carboxylic Acids". Journal of Organic Chemistry. 59 (12): 3243–3245. doi:10.1021/jo00091a001.
  29. ↑ Davis, Franklin A.; Liu, Hu; Zhou, Ping; Fang, Tianan; Reddy, G. Venkat; Zhang, Yulian (1999). "Aza-Darzens Asymmetric Synthesis of N-p-(Toluenesulfinyl)aziridine 2-Carboxylate Esters from Sulfinimines (N-Sulfinyl Imines)". Journal of Organic Chemistry. 64 (20): 7559–7567. doi:10.1021/jo990907j.
  30. ↑ Davis, Franklin A; McCoull, William; Titus, Donald D. (1999). "Asymmetric Synthesis of α-Methylphosphophenylalanine Derivatives using Sulfinimine Derived Chiral Enantiopure Aziridinyl-2-phosphonates". Organic Letters. 1 (7): 1053–5. doi:10.1021/ol990855k. PMID   10825956.
  31. ↑ Davis, Franklin A.; Wu, Yongzhong; Yan, Hongxing; McCoull, William; Prasad, Kavirayani R. (2003). "Asymmetric Synthesis of Aziridine 2-Phosphonates from Enantiopure Sulfinimines (N-Sulfinyl Imines). Synthesis of α-Amino Phosphonates". Journal of Organic Chemistry. 68 (6): 2410–2419. doi:10.1021/jo020707z. PMID   12636410.
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