Substituted enecarbamates

The oxazolidinone-substituted olefin Ic (Scheme 3) constitutes another fortunate substrate for the diastereoselective synthesis of a chiral dioxetane , which is of preparative value for the enantiomeric synthesis of 1,2 diols . For example, the photooxygenation of the enecarbamate Ic produces the asymmetric dioxetane 2c in >95% jt-facial diastereoselectivity. The attack of the O2 occurs from the jt face anti to the isopropyl... 

A comparative study involving singlet oxygen, ozone, and 4-phenyl-1,2,4-triazoline-3,5-dione oxidation of chiral oxazolidinone substituted enecarbamates has shed light on the mechanistic intricacies of the oxidative cleavage of alkenyl double bonds.282... 

In 2007, Betzer, Ardisson and co-workers reported their synthesis of discodermo-lide [64] following the Marshall disconnection strategy of C7-C8 acetylide addition and Suzuki cross-coupling at C14-05 (Scheme 32) [53, 54], The synthesis of the key subunits 160 (C1-C7), 161 (C8-C14) and 162 (C15-C24) demonstrated the versatility of the Hoppe crotyltitanation reaction [166-169] in the synthesis of polypropionate motifs, using the incorporated (Z)-0-enecarbamate to configure the requisite alkene substitution patterns [170, 171],... 

Recently, Bach and coworkers reported the photocycloaddition of a-alkyl-substituted enecarbamates 131 to benzaldehyde affording 3-amino oxetanes 132 (Sch. 44) in moderate to good yields (46-71%) [127]. The a-phenyl substituted enecarbamate did not lead to a photocycloaddition... 

Scheme 9 demonstrates the further synthetic application of the thus obtained N,0-acetals. Substitution of the alkoxy or acyloxy group by nucleophiles like enol ethers, enol esters, enamines, other electron-rich olefins, CH-acidic compounds, electron-rich aromatics, isocyanides, trimethylsilyl cyanide, organometallics, vinyl and allyl silanes, hydroxy functions, or trialkylphosphites either catalyzed by Lewis acids or proton acids leads to the product of the amidoalkylation reaction (path a). In the presence of stereocenters as control elements, diasteroselective amidoalkylation reactions can be performed as shown in a large number of examples. On the other side, as Nyberg showed for the first time [196], elimination with formation of enecarbamates [208] and enamides [196,208,209] followed by reaction with electrophiles or nucleophiles (path b) also is possible. 

Amido-substituted methylenecyclopropanes can be used in [2 + 2] photocycloadditions with chromium-alkoxycarbene complexes. (5)-3-(2-Methylenecyclopropyl)-4-phenyloxazolidin-2-one (14) was prepared from pentacarbonyl[A-phenylglycinyl(cyclopropyl)carbene]chro-mium(O) by ring closure with sodium hydride and diphenyl carbonate. Photolysis of a variety of chromium-alkoxycarbene complexes 15 in the presence of two equivalents of optically active enecarbamate under carbon monoxide produced optically active cyclobutanones. The cis- and trani-products, 16 and 17, were formed with a high degree of asymmetric induction at the position a to the oxygen. ... 

Spectroscopic analysis of the diacetyl derivative of 174 was used to determine its structure. The structure was confirmed by a synthesis of 174 [and 175 and 176] involving the cycloaddition reaction of styrene and a nitrone. Resolution of an intermediate and application of Horeau s method before completion of the synthesis provided the absolute configuration of 174 [449]. In a recent synthesis of (-)-174, a key step utilized the hydroboration of an appropriately substituted enecarbamate to introduce the 5-hydroxyl group [450]. 

Numerous alkene derivatives that possess one electron-releasing substituent have been found to react with salt (1). These include enamines, enamides, enecarbamates, enol ethers and enol acetates. Electrophilic substitution of these alkene derivatives occurs readily, yielding iminium salts that have found substantial use in synthesis. ... 

To investigate the effects of various substituents on the a-phosphono enecarbamate core structure, a variety of chloro- or methoxy-substituted substrates 361b-h were prepared and treated with Pd(PPh3)4, K2CO3, and dimethyl fumarate (335) in CH3CN at 70°C. In aU cases, the desired tetrahydrocarbazoles 364 were formed in good to excellent yields (Scheme 79). 

A chiral ligand mediated approach to lithiation-substitutions of allylic amines has also been well developed. Weisenburger and Beak demonstrated that lithiation of doubly protected allylic amines 141 in the presence of the chiral ligand (-)-sparteine (5), and substitution with a variety of electrophiles provided highly enantioenriched enecarbamate products 142 (Scheme 44) [100]. The authors demonstrated that the intermediate organolithium could be viewed as either an aldehyde P-homoenolate or y-lithioamine synthetic equivalent by hydrolysis or reduction and deprotection of the enecarbamates, respectively. 

Because of the difficulty of accessing (-h)-sparteine, an alternative route to the enantiomeric enecarbamate products has been developed [100]. Synthesis of stannanes 149 and 150 by traditional deprotonation-substitution, followed by transmetallation and substitution with electrophiles provided products of the opposite configuration ent-151 (Scheme 46). Accessing this stereoisomer is possible because of the substitution of lithiated 141 with Me3SnCl occms with inversion and the subsequent transmetallation with retention generates the epimer of hthiated 141. 

Treatment of enecarbamate 344 with sodium azide and ceric ammonium nitrate (CAN) in acetone furnished azidocarbazole 345. The low yield in this oxidative cychzation reaction is due to formation of the diastereomer consisting of stereochemical inversion at the azide-substituted carbon. At this point, azide reduction employing the Staudinger conditions of triphenyl-phosphine in a mixture of water and THF led to an amine, which was subjected to trichloroacetyl chloride in a solution of dichloromethane and triethylamine to yield amide 346 (Scheme 49). 

Enantioselective organocatalyzed inverse-electron-demand hDA reactions of p,y-unsaturated a-keto esters with enecarbamates (14CEJ16753) or with allylsilanes (14AGE6131) led to 2-substituted 3,4-dihydro-2ff-pyrans and of a,P"Unsaturated aldehydes with acyl phosphonates gave access to... 

The (/ )-BlNOL-based phosphoric acid catalyst 94 was recently applied in a related three-component Mannich-type reaction of aldehydes 2 with p-nitroaniline 95 and enecarbamates 96a-b by Masson and Zhu to obtain the corresponding amino-substituted N,0-acetals, which were reduced in situ to the fln -l,2-disubstituted 1,3-diamines 97a-f (Scheme 5.41) [57]. The reduced Mannich products were obtained in moderate to high yields (62-97%) and good to excellent ee. 

Gong and co-workers [80] developed an organocatalytic enantioselective nucleophilic substitution reaction of 3-hydroxyoxindoles with enecarbamates catalyzed by chiral phosphoric acid, which provided a new approach for the preparation of 3,3 -disubstituted oxindoles with a quaternary all-carbon stereogenic center. They demonstrated the efficiency of this methodology in the enantioselective construction of (-h)-folicanthine (198) (Scheme 17.33). Under the optimized reaction conditions, the enantioselective substimtion reaction of 194 with enecarbamate 195 using catalyst 196 afforded 197 in 82% yield and 90% ee. Compound 197 was then transformed into (+)-folicanthine (198) by a 12-step sequence in 3.7% overall yield. 

Kobayashi and coworkers reported a highly enantioselective approach to aldol-type products via addition of enecarbamates (85a-c) to ethyl glyoxylate (12) and subsequent hydrolysis (Scheme 17.17) [22]. A complex prepared from CuCl04 4CH3CN and chiral diimine (86) was found to catalyze additions in excellent yields and enantioselectivities. In reactions of a-substituted enecarbamates, E-enecarbamates (85b) gave antiadducts, while Z-enecarbamates (85c) provided syn adducts. Diastereo-and enantioselectivities were outstanding in both cases, even at very low catalyst loadings. 

The endoselectivity in the formation of 195 is significantly higher than that observed for the reaction of the unsubstituted endocyclic enecarbamates with mono substituted ketenes. When alkylketenes are used in the reaction of substituted endocyclic enecarbamates high stereoselectivity is also observed... 

We reported our first results with the Heck-Matsuda reaction in the late 1990s for the arylation of chiral, nonracemic, endocyclic enecarbamates 9 to produce the aryl pyrroUdines 8. These interesting intermediates were further applied in the total synthesis of several fully substituted A -heterocycles with pharmacologically active compounds such as the antibiotic and hypertensive pyrrolidine alkaloid codonopsinine 6, and the antitrypanosomal Schramm s C-azanucleoside 7 (Scheme 4). ... 

Chiral Brpnsted acids have also been shown to effectively catalyze the Mannich reaction between aldehydes, anilines, and enecarbamates [100]. Here, the application of enecarba-mates as nucleophilic species instead of ketones gives access to enantioenriched 1,3-diamines after subsequent reduction in situ with sodium cyanoborohydride. The potential of this approach was demonstrated by reacting various aromatic or aliphatic aldehydes and substituted enecarbamates with para-nitroaniline in the presence of the chiral phosphoric acid catalyst 150 (Scheme 11.34). 

An alternative way to form meso-substituted dipyrrolyl alkanes was discovered by Yadav et al, using InBrs (5 mol%) to catalyze the reaction between pyrroles and cyclic enol ethers or enecarbamates [133] (Figure 8.57). InCl3 (10mol%) was also reported to be equally effective. 

Their reaction setup requires the conversion of aldehyde 122 and aromatic amine 123 into the imine prior to treatment with catalyst 99c (a phosphoric acid) and enecarbamate (and a final reduction of the hemiaminal intermediate 125). This three-component reaction can thus be classified as a sequential reaction. Notably, the authors also used aliphatic aldehydes successfully. Using substituted enecarbamates gave 1,2-disubstituted 1,3-diamines 126 with excellent anti-selectivity. They proposed a transition state in which the chiral phosphoric acid activates not only the imine as a Bronsted acid, but also the (i )-enecarbamate as Bronsted base, resulting in a pseudo-intramolecular Si-face attack to the imine [69]. 

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