Methylation with dimethylsulfoxonium methylid

C-Methylation products, o-nitrotoluene and p-nitrotoluene, were obtained when nitrobenzene was treated with dimethylsulfoxonium methylide (I)." The ratio for the ortho and para-methylation products was about 10-15 1 for the aromatic nucleophilic substitution reaction. The reaction appeared to proceed via the single-electron transfer (SET) mechanism according to ESR studies. 

The direct irradiation of the parent coumarin in the presence of alkenes results only in an inefficient photodimerization and [2 + 2]-photocycloaddition. Lewis acid coordination appears to increase the singlet state lifetime, and leads to improved yields in the stereospecific [2 + 2]-photocycloaddition [95]. Alternatively, triplet sensitization can be employed to facilitate a [2 + 2]-photocycloaddition. Yields of intramolecular [2 + 2]-photocycloadditions remain, however, even with electron-rich alkenes in the medium range at best. The preference for HT addition and for formation of the exo-product is in line with mechanistic considerations discussed earlier for other triplet [2 + 2]-photocycloadditions [96, 97]. Substituted coumarins were found to react more efficiently than the parent compound, even under conditions of direct irradiation. 3-Substituted coumarins, for example, 3-methoxy-carbonylcoumarin [98], are most useful and have been exploited extensively. The reaction of 3-ethoxycarbonylcoumarin (100) with 3-methyl-l-butene yielded cleanly the cyclobutane 101 (Scheme 6.36) with a pronounced preference for the exo-product (d.r. = 91/9). Product 101 underwent a ring-opening/ring-closure sequence upon treatment with dimethylsulfoxonium methylide to generate a tetrahydrodibenzofur-an, which was further converted into the natural product ( )-linderol A (102) [99]. 

With fram-crotonic acid methyl ester, dimethylsulfoxonium methylide forms a cyclopropane stereoselectively (Figure 9.3, bottom). Therein, the methyl group and the COzMe group retain the trans orientation they had in the crotonic ester. Thus, the fnms-crotonic ester is cyclopropanated with complete retention of the configuration. 

Miscellaneous. A vinylic sulfoxide was prepared firom (J )-methyl p-tolyl sulfoxide and benzophenone. Cyclopropanation of the double bond with Dimethylsulfoxonium Methylide gave a good diastereoselectivity (eq 14). ... 

A short enantiospecific total synthesis of (+)-aphanamol I and II from limonene was achieved and the absolute stereochemistry of I and II established in the laboratory of B. Wickberg. The key steps were a de Mayo photocycloaddition, a Corey-Chaykovsky epoxidation and finally a base-cataiyzed fragmentation of the j,8-epoxyalcohol intermediate. Upon treating the photocycloadduct with dimethylsulfoxonium methylide, only the endo epoxide diastereomer was formed due to the steric hindrance provided by the methyl and isopropyl groups. 

The cyclopropanation reaction is greatly facilitated by electron withdrawal from the alkenic double bond. Diethyl isopropylidenemalonate (40) consequently reacts with dimethylsulfoxonium methylide (33) to give the cyclopropane (41) in 91% yield in one hour, whereas ethyl 3-methyl-2-butenoate (42) only forms 9% of the cyclopropane (43) in the same period (Scheme 17). 

Dehydroamino acids derived from (57 ,6S )-4-(terr-butoxycarbonyl)-5,6-diphenyl-2,3,5,6-tetra-hydro-4//-l,4-oxazin-2-onc are cyclopropanated with the ylide from [(diethylamino)methyl]-phenyljoxosulfonium tetralluoroborate in high chemical and optical yields. The products obtained can be transformed into enantiomerically pure (lS )-l-aminocyclopropanecarboxy-latesl04. Also, optically pure methyl (SS)-3,3-diphenyl-(4-tolylsulfinyl)propenoate reacts with dimethylsulfoxonium methylide to give the corresponding (l7 )-cyclopropane derivative105. 

Cyclopropanation.1 The key step in a biomimctic synthesis of (i)-colchicine (4) is a regio- and stereoselective reaction of the tricyclic I, prepared in several steps from 5-bromo-2-methoxyphenol, with dimethylsulfoxonium methylide to give a single product (2) in 75% yield. When treated with trifluoroacclic acid at 25°, this product rearranges in 89% yield to the a-tropolone O-methyl ether 3. This product is converted into ( )-co chicine (4) in four known steps. 

Synthesis of racemic naproxene Friedel-Crafts acylation (aluminum chloride - nitrobenzene) of p-naphthol methyl ether affords 2-acetyl-6-methoxy naphthalene, which, when treated with either dimethyl sulfonium or dimethylsulfoxonium methylide, gives 2-(6-methoxynaphthalen-2-yl)propylene oxide. Treatment of the latter with boron trifluoride etherate in tetrahydrofuran gives 2-(6-methoxynaphthalen-2-yl)propionaldehyde, which is oxidized using Jones reagent (4 M chromic acid) to yield the racemic 2-(6-methoxynaphthalen-2-yl)propionic acid. 

High stereoselectivity and yield were also observed in the reaction of dimethylsulfoxonium methylide with an optically pure methyl a-(p-tolylsulfinyl) acrylate [481],... 

Dimethylsulfoxonium methylide. 14,152 15,147 16,146 17,126-127 18,148 19,139 Polyhomologation. The ylide provides the methylene unit in chain extension of triorganoboranes. Besides oxidative workup to generate alkanols, the replacement of the boron atom by a hydroxylated carbon on reaction with dichloromethyl methyl ether gives compounds with trident carbon chains. 

Dimethylsulfoxonium methylide adds to bicyclic a,/ -unsaturated y-lactams with excellent diastereofacial selectivity (d.r. >95 5) to provide tricyclic compounds80. Interestingly, lactams lacking the angular methyl group react with complete reversal of diastereoselectivity. 

Anthracene heated 15 hrs. at 100° with excess dimethylsulfoxonium methylide 9-methylanthracene. Y 45%. Also O- and N-methylation s. H. Metzger, H. Konig, and K. Seelert, Tetrah. Let. 1964, 867. 

Methylsulfinylmethane [dimethyl sulfoxide, DMSO, (013)280] reacts with methyl iodide (CH3I) to produce the trimethylsulfoxonium iodide [(013)380 I ]. The sulfoxonium iodide can be induced to eliminate hydrogen iodide (HI) by treatment with sodium hydride (NaH) in methylsulfinylmethane [dimethyl sulfoxide, DMSO, (CH3)2S0] to generate the corresponding dimethylsulfoxonium methylide [(CH3)2S (0)CH2-] (Equation 9.48). 

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