Enecarbamates synthesis

In related studies, Terada described the synthesis of optically pure piperidines via a tandem aza-ene-type reaction/cyclization sequence (Scheme 5.18) [32]. The reaction of a monosubstituted enecarbamate and an N-acyl aldimine affords aza-ene-type intermediate 5, which reacts with a second equivalent of enecarbamate to give aldimine 6. Subsequent intramolecular cyclization terminates the aze-ene-type reaction sequence to furnish trans-piperidine 7 in high enantio- and diasterio-selectivities. 

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... 

As already hinted at above, chiral dioxetanes, obtained through the highly stereoselective [2 + 2] cycloaddition of singlet oxygen to the chiral enecarbamate, provide a convenient preparation of optically active 1,2 diols as building blocks for asymmetric synthesis (Scheme 5) . Reduction of the dioxetane 2c by L-methionine, followed by release of the oxazolidinone auxiliary by NaBH4/DBU reduction, affords the enantiomerically pure like-5 diol (for additional cases, see Table 4 in Reference 19e). 

A promising unprecedented application of the chiral enecarbamates Ic in asymmetric synthesis is based on the ship-in-the-bottle strategy, which entails the oxidation of these substrates in zeolite supercages . In this novel concept, presumably dioxetanes intervene as intermediates, as illustrated for the oxidation of the chiral enecarbamate Ic in the NaY zeolite (Scheme 6). By starting with a 50 50 mixture of the diastereomeric enecarbamates (45, 3 R)-lc and (45, 3 5 )-lc, absorbed by the NaY zeolite, its oxidation furnishes the enantiomerically enriched (ee ca 50%) S -methyldesoxybenzoin, whereas the (4R,3 R)-lc and (4R,3 S)-lc diastereomeric mixture affords preferentially (ee ca 47%) the R enantiomer however, racemic methylbenzoin is obtained when the chirality center at the C-4 position in the oxazolidinone is removed. Evidently, appreciable asymmetric induction is mediated by the optically active oxazolidinone auxiliary. 

A cyclization of enecarbamates leads to the synthesis of pyrrolo[2,3-f]pyridines (Equation 40) <2005TL8877>. The reaction is catalyzed by a copper(l) iodide/L-proline catalyst system. 

As described above, the carbon-carbon bond formation at the a-position of amines using anodically a-methoxylated carbamates as the starting compounds is highly useful for the synthesis of alkaloid type compounds, however, this method is limited only to the bond formation at the a-position. On the other hand, it has been found that the elimination of methanol from the a-methoxylated carbamates 47 yields the corresponding enecarbamates 48 in high yields 30). 

A diastereoselective synthesis of all. fy -2,3,6-trisubstitutcd tetrahydropyran-4-ones 1039 via an intramolecular Prins cyclization of enecarbamates 1038 with aldehydes is used during a formal synthesis of (+)-ratjadone (Equation 403) <2004JA12216>. Similarly, tetrahydropyran-4-ones bearing quaternary centres a-to the carbonyl are accessible via a Lewis acid-mediated Prins cyclization of silyl enol ether substrates <2004JA15662>. 

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],... 

As shown in Scheme 33, the synthesis of the C1-C7 amide 160 began with a Hoppe crotyltitanation reaction between the aldehyde 17 and the (R)-crotyltitanium 163, prepared in situ (crotyl diisopropylcarbamate with sBuLi/(-)-sparteine/ Ti(0/Pr)4), to give O-enecarbamate 164 (>30 ldr) [166-169], Ozonolysis and HWE chain extension was followed by an Evans-Prunet 1,4-addition to install the C5-stereocentre to complete 160 [103], The synthesis of the C8-C14 subunit 161 started with an elegant installation of the C13-C14 (Z)-olefin. Deprotonation of the dihydrofuran 165, available in three steps from bromo alcohol 166, with fBuLi and transmetallation with Me2CuLi LiCN, and subsequent 1,2-cuprate transfer gave the... 

Despite the large utility of enamines in organic synthesis, the study of the electrochemistry of enamines and especially the application to synthetic organic reactions has been a rather minor area in electroorganic chemistry, and only a few studies have been reported. In this review these works are summarized and electrochemical synthesis and some reactions of a,/ -unsaturated urethanes (enecarbamates) are also described, since their chemical reactivity is considerably similar to that of the enamines. 

Fuwa H, Sasaki M (2007) An efficient method for the synthesis of enol ethers and enecarbamates. Total syntheses of isoindolobenzazepine alkaloids, lennoxamine and chilenine. Chemlnform 5 1849-1853... 

The preparation of 3-pyrroline was recently reported in Organic Syntheses The protected form, N-Boc-3-pyrroline, has been used effectively in Heck arylations for the preparation of various 4-aryl endocyclic enecarbamates. It has also been used in the preparation of regioisomeric 3-hydroxyisoxazolinyl prolines which are medicinally active. The catalytic asymmetric hydroformylation of N-Boc-pyrroline has been investigated. N-Boc-pyrroline has also been utilized in the synthesis of various antibacterial compounds. ... 

Numerous examples of the application of this synthetically useful reaction have been reported. Illustrative examples include the synthesis of eneamides and enecarbamates [72,73] and a large series of pyrrolidine, piperidine, and perhydroazepine derivatives [72,7 77],... 

The total synthesis of amaryllidaceae alkaloid buflavin was achieved in the laboratory of A. Couture by utilizing a Horner-Wittig reaction between a biaryl aldehyde and a metalated carbamate. The diphenyl phosphine oxide carbamate was deprotonated with n-BuLi. To the resulting metalated carbamate was added the solution of the biaryl aldehyde in THF. The reaction afforded the corresponding (Z)- and ( )-enecarbamates in good yield and with high -selectivity. 

Lebrun and coworkers reported a convenient synthesis to a range of phenanthroindo- and quinolizidine natural products [62]. In this approach, the alkaloids (+)-antofine [( )-3] (n-1) and (+)-cryptopleurine [(+)-5] (n=2), were synthesized by Pictet-Spengler cyclization of 72 [2-arylmethyl-piperidine (n=2) and -pyrrolindine (n=l)], Scheme (7). The intermediate compounds were obtained by sequential iV-deprotection-reduction of the parent enecarbamates 71, which were obtained from Homer reaction of phosphorylated carbamates 70 with the appropriate aldehyde (69). 

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. ... 

Two more complex examples of this reaction type are used in work on the total synthesis of quinocar-cin and gelsemine. A vinyl sulfide is employed as nucleophile in an Af-acyliminium cyclization to produce the bridged substructure of quinocarcin (equation 96).A genuine equivalent of the Mannich reaction is put to practice in a synthetic approach to gelsemine (equation 97). The iminium intermediate, simply generated by protonation of the enecarbamate, apparently reacts only with the enol shown in (128). 

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