Sulfoxide imination

Again, sulfoxide imination is stereospecific and free NH-sulfoximines such as 9 may be obtained with retention of stereochemistry by cleavage of the nosyl protecting group (Scheme 2.1.1.5) [23]. 

Scheme 6.5. Sulfoxide imination using silver-terpyridine catalyst.

When compared to aziridination or sulfoxide imination, efficient amidation of C-H bonds is a more formidable task since it involves the activation of relatively inert C-H bonds. With an increase in the difficulty of the reaction comes an increase in the value of products, as many are derived from cheap simple hydrocarbons. In addition to making more valuable materials in fewer steps, a better mechanistic understanding of nitrene transfer can also be gleaned, leading to the development of efficient catalysts. 

C-Methylation. Methyl iodide is an active alkylating agent employed in the C-methylation of carbanions derived from ketones, esters, carboxylic acids, amides, nitriles, nitroalkanes, sulfones, sulfoxides, imines, and hydrazones. The quantity of methyl iodide utilized in methylations varies from a slight (1.1 equiv) to a large excess (used as solvent). 

Addition of Methyl Sulfoxides Reactions with Imines... 

To a solution of 1 equiv of( + )-(R)-methyl 4-tolyl sulfoxide (1) inTHF is added a solution of 1 equiv of LDA at 0°C and, after cooling to —78 C, a solution of 1 equiv of an appropriate imine 2. Addition is usually complete within 10 min. The reaction is quenched with dilute HCI, extracted with CH,C12 and the extracts are dried and evaporated. The products are purifed by Hash chromatography (silica gel). The main diastcreomer can be isolated by crystallization from cyclohexane. No further preparative details are available. 

Since these adducts undergo reductive desulfuration with Raney nickel, optically active aryl methyl sulfoxides are versatile reagents for the conversion of imines to optically active amines. 

Lithium and zinc tert-butyl phenylmethyl sulfoxide (1) and A-phenyl imines 2, in which the substituent R is alkenyl or aryl, react at —78 °C over 2 hours with high anti diastereoselection (d.r. >98.5 1.5)6. Shorter reaction times result in poorer yields, due to incomplete reaction. In contrast, the reaction of the sulfoxide anion with benzaldehyde is complete after 5 seconds, but shows poor diastereoselection. When the substituent R1 or R2 of the imine 2 is aliphatic, the substrates exhibit poor chemical reactivity and diastereoselection. The high anti diastereoselection suggests that if a chelated cyclic transition state is involved (E configuration of the imine), then the boat transition state 4 is favored over its chair counterpart 5. 

Mainly sulfoxide groups are introduced as chiral auxiliaries for the modification of a,/J-unsat-urated enones (see Section D.1.5.3.5.). Chiral imine derivatives have also been used (see Section D.1.5.3.1.). Various chiral alcohols, and in particular 8-phenylmenthol, have been successfully used as auxiliaries, mainly in two-fold Michael additions to a,/ -unsaturatcd esters. 

J-Enamino and /i-imino sulfoxides are formed by the reaction of lithioenamines with sulfinate ester 1990. In the six examples reported, enamines were formed exclusively in three cases (equation 20), a mixture of enamines and imines in two cases, and an imine exclusively in one case (equation 21). 

Colona and coworkers oxidized a variety of alkyl aryl and heterocyclic sulfides to the sulfoxides using t-butyl hydroperoxide and a catalytic amount of a complex (97) derived from a transition metal and the imines of L-amino acids. Of the metals (M = TiO, Mo02, VO, Cu, Co, Fe), titanium gave the highest e.e. (21%), but molybdenum was the most efficient catalyst. The sulfoxides were accompanied by considerable sulfone125. 

The above-described structures are the main representatives of the family of nitrogen ligands, which cover a wide spectrum of activity and efficiency for catalytic C - C bond formations. To a lesser extent, amines or imines, associated with copper salts, and metalloporphyrins led to good catalysts for cyclo-propanation. Interestingly, sulfinylimine ligands, with the chirality provided solely by the sulfoxide moieties, have been also used as copper-chelates for the asymmetric Diels-Alder reaction. Amide derivatives (or pyridylamides) also proved their efficiency for the Tsuji-Trost reaction. 

The synthesis of sulfoximides and sulfimides has attracted considerable attention in recent years due to the potential utility of these compounds as efficient auxiliaries and chiral ligands in asymmetric synthesis (reviews [86-88]). Transition metal-catalyzed nitrene transfer to sulfoxides and sulfides is an efficient and straightforward way to synthesize sulfoximides and sulfimides, respectively. Bach and coworkers reported the first iron-catalyzed imination of sulfur compounds with FeCl2 as catalyst and B0CN3 as nitrene source. Various sulfoxides and sulfides were... 

In pyridine- X-C interactions, the C - X moiety is roughly coplanar with the pyridine and the two C-N- X angles are approximately 120° [129,143, 144]. The same holds for other nitrogen heteroaromatics (e.g. pyrazine, quinoline, etc.) [145-147]. A carbonyl group pins the donors after a trigonal planar geometry and works either as a mono- [148,149] or bidentate XB acceptor [150]. Sulfoxides behave similarly [151,152] and imines form XB along the expected axis of the lone pair [153]. 

The synthesis of 4,5-diaryl-6-phenylsulfanyl-2,3-benzo-l,3a,6a-triazapentalenes 239 through Pummerer-type reactions of (benzotriazol-l-yl)allylic sulfoxides 238 with trifluoroacetic anhydride in THF has been reported (Equation 35) <2002EJ0493>. Similarly, unstable solid imines 240 treated without purification with trifluoroacetic anhydride (TFAA) provide 241 (Equation 36) <2003TL7507>. 

Oxidation of the substituted isothiazolium-2-imines 7 with H2O2 in AcOH gave stable 3-hydroperoxy-2-benzoylaminohexahydro-l,2-benzisothiazole 1-sulfoxide rac cis 8 and the sultam 9. The sultam 9 could then be converted into novel hydroxysultams 10 by reduction with Na2S03 / H2O in excellent yields. If necessary, 10 could be reoxidised to 9 with H2O2 <00JPR291>. 

In addition, a recent report details a very efficient nonenzymatic method for the asymmetric oxidation of sulfides this employs an organo-vanadium species featuring the imine (38) (Scheme 25)[111]. A second, complementary strategy for the preparation of optically active sulfoxides involves the enantioselective oxidation of racemic sulfoxides. ... 

Abstract This chapter principally concerns oxidations of organic substrates containing N, O, S, P, As and Sb. Oxidations of amines are covered first, including primary amines to nitriles or amides secondary amines to imines or other products tertiary amines to N-oxides or other prodncts (Section 5.1) and the oxidation of amides (5.2). Oxidation of ethers to esters or lactones follows (5.3), then of sulfides to sulfoxides or sulfones (5.4) and of phosphines, arsine and stibines to their oxides (5.5). A final section (5.6) concerns such miscellaneous oxidations not covered by other sections in the book. 

Oxidation of chiral sulfonimines (R"S02N=CHAr)and chiral sulfamyl-imines (R RNS02N=CHAr)affords optically active 2-sulfonyloxaziridines and 2-sulfamyloxaziridines, respectively. These chiral, oxidizing reagents have been used in the asymmetric oxidation of sulfides to sulfoxides (15-68% ee), 11-13 selenides to selenoxides (8-9% ee] enolates to a-hydroxycarbonyl compounds (8-37% ee) and in the asymmetric epoxidation of alkenes (15-40% ee)... 

JHC671> in a similar fashion to the precedent (DMSO = dimethyl sulfoxide). However, the quinoxalinone 18 (R = Me, X = GeHsO) exists only in the imine form due to the steric hindrance of the methyl group <1997JHC773>. 

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