Homoallylic carbamates

Hydroxy-l-alkenyl diisopropylcarbamates 2 (X = OCb), in this respect, occupy a medium position since they are stable in strongly acidic and basic protic solvents. For deblocking vinyl carbamates, the presence of catalytic amounts of mercuric or palladium(II) salts is required. Due to this stability, several reactions of homoallylic alcohols, proceeding with high diastereo-selectivity, e g., epoxidation, are applicable in order to introduce further hetero-substituents. 

Allylic carbamates have also been cyclized to carbamate-linked fused-ring aziridines. The cyclization of homoallylic carbamates to the corresponding aziridines has not been successful until a recent report <06CC4501>. The reaction of homoallylic carbamate 63 with a rhodium catalyst and iodosobenzene provides moderate yields of the fused-ring aziridine 64. The major byproduct of this reaction is the C-H insertion product 65. The relative amounts of the aziridine to the C-H insertion product could be modulated by the choice of rhodium catalyst. The use of Rh2(OAc)4 provides a 68 14 ratio of aziridine C-H insertion product, while Rh2(oct)4 provides a slightly better 71 6 ratio. 

In the case of cyclopentenyl carbamate in which a directive group is present at the homoallyl position, the cationic rhodium [Rh(diphos-4)]+ or iridium [Ir(PCy3)(py)(nbd)]+ catalyst cannot interact with the carbamate carbonyl, and thus approaches the double bond from the less-hindered side. This affords a cis-product preferentially, whereas with the chiral rhodium-duphos catalyst, directivity of the carbamate unit is observed (Table 21.7, entry 7). The presence of a hydroxyl group at the allyl position induced hydroxy-directive hydrogenation, and higher diastereoselectivity was obtained (entry 8) [44]. 

Iodine is known to catalyze the condensation of aldehydes, benzyl carbamate and allyltrimethylsilane to homoallylic amines. However, in this case the involvement of an in sitn prepared [MejSi] species was suggested to be the active catalyst [235], An iodine catalyzed acetalization of carbonyl compounds was reported, where the active catalyst was believed to be hydroiodic acid [236],... 

Solvolysis of Diels-Alder adducts provides a useful means of preparing a variety of nitrogen-containing compounds. For instance, the hydrolysis of A Cbz or A -Ts bicylic sulfonamides 44 and 112 with NaOH affords the homoallylic carbamate 113 and sulfonamide 114, respectively (Scheme 12) <2000TL3743, 2002TA2407>. Related hydrolysis reactions have also been reported with monocyclic 1,2-dihydrothiazine oxides <2004JOC7198>. 

Homoallylic carbamate esters 3 cyclize to 6-membered carbamates 4 with high 1,3-syn induction. 

The cyclization of carbamate derivatives of unsaturated amines has proven synthetically useful. Cyclizations of carbamates of allylamines containing a terminal vinyl group give oxazolidinone products (equation 60 and Table 17, entries 1 and 2).99,161 Bromocyclizations of systems with a di- or tri-sub-stituted alkene often give mixtures of oxazolidinones and tetrahydrooxazinones,163 while cyclization of an A -cinnamyl carbamate with phenylsulfenyl chloride gave only the oxazolidinone product.163b,163c The stereochemistry of the cyclization of primary carbamates of either allylic or homoallylic amines is low... 

Studies on tethered derivatives of homoallylic alcohols are fewer in number. Iodocyclization of tri-chloroacetimidate derivatives of 4-penten-2-ol (21) gave cis- and franj-dihydrooxazines in an 80 20 ratio,234a 254b while cyclization of the /V-benzenesulfonylcarbamate derivatives (22) provided an 86 14 ratio of cyclic carbamates 253 Cyclization of the N-acylaminomethyl derivatives (23) with mercury(II) tri-fluoroacetate under conditions of kinetic control gave a 75 25 ratio of cis- and rrans-tetrahydrooxazine derivatives, but cyclization under conditions which allowed for equilibration of the organomercury intermediates produced a 6 94 ratio.238... 

The basic Markovnikov selectivity pattern is partially or fully overrun in the presence of neighboring coordinating groups within the olefin substrate (Section 2.2.2). Known functionalities where inversed selectivity can occur include 3-alke-noylamides (e.g. 17 reacts to give a mixture of 18 and 19, Table 3) [43], homoallyl esters and alcohols, allyl ethers (but not necessarily allyl alcohols) [44], allyl amines, allyl amides, or carbamates (cf. 20 to 21) [45], allyl sulfides [46] or 1,5-dienes [47]. As a matter of fact, aldehyde by-products are quite normal in Wacker reactions, but tend to be overlooked. 

Some interesting intramolecular variants have been reported. For example, homoallylic alcohols (e.g. 139) can be treated with sulfamoyl chloride to form the corresponding sulfamates (140), which then engage in a direct intramolecular copper-catalyzed aziridination mediated by iodosylbenzene <02OL2481>. A carbamate tether is also effective in delivering the nitrene center to the olefin, as is the case with the cyclohexenyl derivative 142, which spontaneously cyclizes in the presence of iodosylbenzene <02OL2137>. The acetoxy-aminoquinazolinone 144 is converted to the lactone 145 via intramolecular aziridination upon treatment with lead tetraacetate and hexamethyldisilazane (HMDS) <02TL2083>. 

An alternative procedure is available for the preparation of iodocarbonates which utilizes homoallylic carbamates as the starting material. For example, (/f )-( )-5-(aminocarbonyloxy)-l-benzyloxy-2,8-nonadiene [12, R1 = ( )-CH2OBn R2 = (CH2)2CH = CH2 R3 = H]9 with two equivalents of iodine in a two-phase medium consisting of diethyl ether and sodium hydrogen carbonate solution at 20 CC affords the corresponding cyclic iodocarbonate 13, a precursor of 1,3,5-triols1 °, in 76% yield and 93 7 (cis1,traits ) selectivity. 

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 halocyclization of a homoallylic carbamate 718, containing (S)-l-phenylethylamine as chiral source, similarly affords a 50 50 diastereomeric mixture of tetrahydro-2//-l,3-oxazin-2-ones 8, which can be easily separated by chromatography and identified by 1 H-NMR spectroscopy. In compounds 8, the substituent at C-6 displays a strong tendency to occupy the equatorial position in both isomers. 

Homoallylic carbamates also cyclize smoothly with sodium hydride to yield 6-membered cyclic carbamates with high l,3-s>v asymmetric induction70-147. The presence of a Z double bond also improves the stereoselectivity to a large extent. 

Azo-ene reactions. The ene reaction provides a powerful method for C-C bond formation with concomitant activation of an allylic C-H bond. A variety of functionalized carbon skeletons can be constructed due to the range of enophiles which can be used. For example, carbonyl compounds give homoallylic alcohols and imino derivatives of aldehydes afford homoallylic amines. The azo-ene reaction offers a method for effecting allylic amination by treatment of an alkene with an azo-diester to afford a diacyl hydrazine which upon N-N cleavage furnishes a carbamate. Subsequent hydrolysis of the carbamate provides an allylic amine. Use of chiral diazenedicarboxylates provides a method for effecting stereoselective electrophilic amination. 

In this connection, intramolecular Michael addition of 0-carbamates to a,3-unsaturated esters (Scheme 60)," iodo cyclization of allylic and homoallylic trichloroacetamidates" or aminomercuration of alkenic carbamates" has been used for the preparation of amino alcohols. 

The 2-butenyltitanium reagents are generated by the deprotonation of an E-2-butenylcarbamate 279 with n-butyllithium and then reaction of the newly formed allylic lithium species 280 with chlorotris(diethylamino)titanium [179]. The 2-bu-tenyltitanium reagent 281 is then combined with aldehydes to produce homoallylic alcohols 282 in high yield and excellent regioselectivity (Scheme 10-93). The enol carbamate moiety is readily converted to a carbonyl group and thus constitutes a homoaldol reaction. 

In the presence of BFj, N-acylimines generated in situ from aldehydes or acetals and carbamates smoothly react with allylsilanes, propargylsilanes, and 2,4-pentadien-ylsilanes to give homoallyl [415], allenylmethyl [416], and 3,5-hexadienyl amines [417], respectively (Scheme 10.146). The three-component coupling reaction with crotyltrimethylsilane proceeds with moderate syn selectivity as in the crotylation of aldehydes [418]. 

The reaction of aldehydes with another titanium complex generated from E-crotyl iV-diisopropyl carbamate, s-BuLi, sparteine 2.5 and Ti(0 -Pr)4 gives anti homoallylic alcohols with a good enantioselectivity [109, 1162, 1163] (Figure 6.29). Addition of allylaluminum reagents to aromatic aldehydes in the presence of Sn(OTf>2 and a chiral amine also gives useful results [842],... 

A tethered aminohydroxylation (TA) reaction extends the utility of carbamate versions of the nitrogen source.29 Combining the nitrogen source with allylic or homoallylic alcohols enabled formation of products not previously accessible. Thus, exposure of 48 to the osmium reagent, in the absence of a chlorinating agent and base, led to cyclized amino alcohol 49. A similar result was observed for homoallylic alcohol derivative 50. 

Transpositional displacements. Based on the displacement of allylic carbamates alkenes containing both allylic and homoallylic silyl substituents are accessible. ... 

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