From Acyclic Carbamates

A strategy involving the intramolecular cyclization of acyclic urethanes as a key step has been widely employed since the first synthesis of this class of compounds.  

The reaction of ethyl A-arylcarbamates 3 with l-bromo-3,3-dimethyl-2-buta-none or l-bromo-3-ethyl-3-methyl-2-pentanone 4 in the presence of lithium bis(trimethylsilyl)amide (LiHMDS) results in the one-step synthesis of 3-aryl-5-ferf-butyl-2(3/T)-oxazolones 7 in fair to good yields (Fig. 5.2 Table 5.1, Fig. 5.3). This method is efficient for the preparation of bulky 5-substimted-2(37f)-oxazo-lones. 

The A7-(a-hydroxyphenacyl)urethanes 8 react smoothly with aromatics in concentrated sulfuric acid to give Friedel-Crafts type products 9, which are readily converted into 4-aryl-5-phenyl-2(3/l)-oxazolones 10 on heating or by treatment with phosphorus pentachloride (Fig. 5.4).  

Treatment of l,3-dihalo-2-propyl and 2,3-dichloropropyl A7-arylcarbamates 11 and 14 with ammonium fluoride results in the regioselective transformation to the 2(3f/)-oxazolones 12 and 15 or to the exocyclic methylene derivatives 13 and 16 depending on the temperature (Fig. 5.5).  

TABLE 5.1. SYNTHESIS OF 3-ARYL-5-tert-BUTYL-2(3H)-OXAZOLONES FROM ETHYL A-ARYLCARBAMATES AND a-BROMO KETONES  

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Diastereoselective Synthesis of 2-Oxazoiidinones and Tetrahydro-2//-l,3-oxazin-2-ones from Acyclic vV-AIlyl and A-Homoallyl Carbamates with 1,2- and 1,3-Asymmetric Induction... 

The intermolecular coupling of lactams and acyclic amides has also been reported. Reactions of carbamates with aryl halides occurred in the presence of catalysts ligated by P(/-Bu)3.78 Both carbamates and amides coupled with aryl halides in the presence of a catalyst bearing Xantphos.90 In addition, the coupling of lactams with aryl halides has been successful. A combination of Pd(OAc)2 and DPPF first formed A-aryl lactams in good yields from 7-lactams, but the arylation of amides was improved significantly by the use of Xantphos (Equations (20) and (21)).90 91 The reaction of aryl halides with vinyligous amides has also been reported 92... 

In contrast, reactions catalyzed by la were typically conducted with added [Ir (C0D)C1]2 to trap the K -phosphoramidite ligand after dissociation, and thereby, to leave the unsaturated active catalyst. Under these conductions, as much as half of the iridium in the system is present in an inactive acyclic species. In contrast, when ethylene adduct lb is used as the catalyst, all of the iridium belongs to the active metalacyclic species. Hartwig and coworkers have recently taken advantage of the increased availability of the active catalyst generated from lb to develop new allylic substitution reactions. These new processes include the reactions of carbamates, nitrogen heterocycles, and ammonia. 

Surprisingly it was reported that when potassium cyanate is substituted for sodium cyanate the yields of carbamates are reduced to less than 5 %. The reason for this drastic effect is not known at this time. In addition, the use of other alkali or alkaline metal cyanates in this reaction has not been investigated. The Loev [28] procedure appears applicable to the synthesis of carbamates from primary, secondary, and tertiary alcohols (2 hr reaction time affords 60-90% yields), cyclic and acyclic 1,3-diols, phenols, oximes, ald-oximes, and ketoximes, and primary, secondary, and tertiary mercaptans. Carbamates could not be obtained from diphenylethylcarbinol (dehydrated to 1,1-diphenylethylene) or trichloro- and trifluoromethylcarbinols. 

Related reactions of acyclic unsaturated amide derivatives S show a reversal of the diastereofa-cial selection according to the geometry of the double bond. This is in contrast to the carbamate series (vide infra)13 which is dependent on the nature of the nucleophile68. The most remarkable feature is the formation of 1,2-syvj-products 6B from the A-isomers. This may be best explained by the steric repulsion between the ester and acyl groups. This complementary and effective diastereoselection provides a stereodivergent synthesis of 2,3-disubstituted piperidines (see also Section D.7.3.1.1.2.2.). 

The use of enol silanes" and allylsilanes - as rr-nucleophiles usually leads to acyclic products. The enantiomerically pure IV-acyliminium precursors (131) and (132) are prepared from a-amino acid derivatives. Reaction with allylsilane under the influence of TiCU proceeds with 60% stereoselectivity in the case of carbamate (131) however, the precursor (132) reacts indiscriminately under these circumstances (equations 99 and 100). A more complex allylsilane (133) reacts with iminium precursor (134) in the presence of EtAlCb to produce carbamate (135) as a single diastereomer in 48% yield (equation 101 ). ... 

Aryne Annulation. Treatment of o-(trimethylsilyl)aryl triflates with TBAT results in the formation of ben-zyne intermediates. Fluoride-induced 1,2-eliminations of o-(trimethylsilyl)aryl triflates, which are readily prepared from phenols, have been shown to provide the respective aryne products, which, at room temperature, precipitously undergo cycloaddition in the presence of Diels-Alder adducts, including, but not limited to, tethered acyclic dienes, tethered enynes (eq 15), azomethine imines (eq 16),ene carbamates, and acetamidoacry-lates (eq 17). ... 

In 1992 Murahashi, Hosokawa, and co-workers described the anti-Markovnikov oxidative addition of amides and carbamates to electron-deficient olefins by applying a palladium and copper cooperative catalysis under oxygen atmosphere [41]. The proposed mechanism involved a ff-bonded palladium(II) intermediate resulting from the addition of the nucleophile to the olefin, and subsequent ) -palladium hydride elimination to yield the functionalized alkene. Interestingly, both lactams and cyclic carbamates gave predominantly the corresponding E-enamide derivatives. Acyclic amides, conversely, afforded ElZ mixtures of products. The addition of a catalytic amount (5 mol%) of hexamethylphosphoric triamide (HMPA) was found notably beneficial for the reaction of 5-membered lactams and reduced the reaction time of such particular oxidative amidations (Scheme 2). 

Electrophilic Cyclization of Trichloroacetimidates. Trichloroacetimidates derived from allylic " and homoallylic alcohols undergo electrocyclic ring closure when treated with a source of I" " (eq 5). Cyclization can also be triggered via the Lewis acid-mediated opening of epoxides. In at least one case the imidate proved more reactive than related reactions using carbamates. These are useful methods for the stereoselective introduction of nitrogen into cyclic and acyclic systems. 

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