Intramolecular carbamate oxidations

The use of a nitrogen nucleophile in the side chain (as an amide) also leads to an intramolecular 1,4-addition under the standard conditions for the palladium-catalyzed 1,4-oxidation reactions52. Nitrogen nucleophiles employed for this reaction comprise tosy-lamides, carboxamides, carbamates and ureas. The reactions are run in acetone-acetic acid with p-benzoquinone (BQ) as the oxidant. In most cases highly stereo- and regioselective reactions were obtained and some examples are given in Table 3. 

Reduced pyrrole derivative 130 is available from the oxidation of carbamate 129. The reaction proceeds via intramolecular participation of the nitrogen atom of the carbamate function as shown in Scheme 36 (94TH1). 

Similarly, intramolecular participation of nitrogen in the oxidation of carbamates 281 affords bridgehead heterocycle 282 in high yield. 

Preliminary efforts to examine the mechanism of C-H amination proved inconclusive with respect to the intermediacy of carbamoyl iminoiodinane 12. Control experiments in which carbamate 11 and PhI(OAc)2 were heated in CD2CI2 at 40°C with and without MgO gave no indication of a reaction between substrate and oxidant by NMR. In Hne with these observations, synthesis of a carbamate-derived iodinane has remained elusive. The inability to prepare iminoiodinane reagents from carbamate esters precluded their evaluation in catalytic nitrene transfer chemistry. By employing the PhI(OAc)2/MgO conditions, however, 1° carbamates can now serve as effective N-atom sources. The synthetic scope of metal-catalyzed C-H amination processes is thus expanded considerably as a result of this invention. Details of the reaction mechanism for this rhodium-mediated intramolecular oxidation are presented in Section 17.8. 

Intramolecular rhodium-catalyzed carbamate C-H insertion has broad utility for substrates fashioned from most 1° and 3° alcohols. As is typically observed, 3° and benzylic C-H bonds are favored over other C-H centers for amination of this type. Stereospecific oxidation of optically pure 3° units greatly facilitates the preparation of enantiomeric tetrasubstituted carbinolamines, and should find future applications in synthesis vide infra). Importantly, use of PhI(OAc)2 as a terminal oxidant for this process has enabled reactions with a class of starting materials (that is, 1° carbamates) for which iminoiodi-nane synthesis has not proven possible. Thus, by obviating the need for such reagents, substrate scope for this process and related aziridination reactions is significantly expanded vide infra). Looking forward, the versatility of this method for C-N bond formation will be advanced further with the advent of chiral catalysts for diastero- and enantio-controlled C-H insertion. In addition, new catalysts may increase the range of 2° alkanol-based carbamates that perform as viable substrates for this process. 

Like carbene insertions into carbon-hydrogen bonds, metal nitrene insertions occur in both intermolecular and intramolecular reactions.For intermole-cular reactions, a manganese(III) meio-tetrakis(pentafluorophenyl)porphyrm complex gives high product yields and turnovers up to 2600 amidations could be effected directly with amides using PhI(OAc)2 (Eq. 51). The most exciting development in intramolecular C—H reactions thus far has been the oxidative cychzation of sulfamate esters (e.g., Eq. 52), as well as carbamates (to oxazolidin-2-ones), ° and one can expect further developments that are of synthetic... 

The reaction of ( , )-2,4-octadecadienyl carbamate with thionyl chloride in pyridine at 15 "C yields only one stereoisomer of the corresponding dihydrothiazine 5-oxide via an /V-sultinyl carbamate intermediate which undergoes intramolecular Diels-Alder reaction with complete stereoselecti vity 96. 

The Weinreb group has reported the only examples of intramolecular [4 + 2] cycloadditions of iV-sulfi-nyl compounds. - For example, diene carbamate (127) could be converted to an -sulfmyl compound which cyclized intramolecularly to dihydrothiazine oxide (128) (Scheme 16). Using the chemistry outlined in equation (54), (128) was transformed stereoselectively to tAreo-sphingosine (129). Similarly, ( ,Z)-diene carbamate (130) was transformed via adduct (131) to erytAro-sphingosine (132). 

An intramolecular version of this methodology was further applied to construction of amino sugars, such as the unnatural C-5 epimer of desosamine (399) (84JOC3243) and deoxyaminopentose (406) (85T1143). When ( , )-diene carbamate 393 was treated with thionyl chloride/pyridine between 0°C and room temperature, a single Diels-Alder adduct (395) was formed in 80% yield. The structure and stereochemistry of this dihydrothiazine oxide were... 

E. Suarez and co-workers prepared chiral 7-oxa-2-azabicyclo[3.2.1]octane and 8-oxa-6-azabicyclo[3.2.1]octane ring systems derived from carbohydrates via an intramolecular hydrogen abstraction reaction promoted by A/-centered radicals. The A/-centered radicals were obtained under mild conditions (Suarez modification) from phenyl and benzyl amidophosphates and alkyl and benzyl carbamate derivatives of aminoalditols by treatment with PIDA/I2 or PhlO/l2. The initial A/-radical undergoes a 1,5-hydrogen abstraction to form an alkyl radical, which is oxidized to the corresponding stabilized carbocation (oxocarbenium ion) under the reaction conditions. The overall transformation may be considered as an intramolecular N-glycosidation reaction. 

Heating of the benzene solution of 44 and K2CO3 induced the intramolecular Sn2 reaction to afford 6-deoxycodeine 45 in 53% yield (Scheme 10). The major side product in this reaction was, as anticipated, diene 46 (30% yield), which was formed by elimination reaction. It was reported that the solvent effect is significant in the Sn2 reaction when this reaction was carried out in acetonitrile, diene 46 was obtained as the major product. Treatment of 45 with methyl chloroformate provided a methyl carbamate, whose allylic oxidation with Se02 in the presence of f-BuOOH introduced the hydroxy group at C-6 to give 19. PCC oxidation of 19, followed by LiAlH4 reduction, provided racemic codeine. 

Diimide reduction of 96, obtained by the enzymatic oxidation of 95 (96% ee) [67], followed by O-acetylation afforded cyclohexene-diol 97 in 47% yield (Scheme 19). Compound 97 was converted into carbamate 98 by S 2 reaction with methylamine and subsequent urethane formation. Regioselective protection of the diol in 98 with TBSC1 afforded 99, which was coupled with bromoisovanillin 54 under the conditions of Mitsunobu to provide 100 (see Sect. 2.2.2). The intramolecular Heck reaction of 100 constructed the benzofuran ring including a quaternary center to afford 101 in 82% yield. Wittig reaction of 101 with Ph3P=CHBr generated vinyl bromide 102 in 49% yield as a mixture of E- and Z-isomers (E Z = ca. 1 2). 

While the majority of Rh-catalyzed C-H amination processes employ hyperva-lent iodine oxidants and sulfonamide derivatives, Lebel and coworkers have demonstrated that /V-tosyloxycarbamates will engage with catalytic Rh2(02CCPh3)4 and K2CC>3 to afford products of intramolecular C-H insertion (Fig. 22) [104, 5, 105]. Similar to Du Bois earlier work involving oxidative cyclization with 1 ° carbamates [94], the /V-tosyloxy derivatives display a strong bias for oxazolidinone formation. Selectivity trends and other mechanistic data support a reaction pathway involving a Rh-nitrene oxidant. Intermolecular amination of simple benzylic substrates... 

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