Allyl carbamate

Allylic acetates are widely used. The oxidative addition of allylic acetates to Pd(0) is reversible, and their reaction must be carried out in the presence of bases. An important improvement in 7r-allylpalladium chemistry has been achieved by the introduction of allylic carbonates. Carbonates are highly reactive. More importantly, their reactions can be carried out under neutral con-ditions[13,14]. Also reactions of allylic carbamates[14], allyl aryl ethers[6,15], and vinyl epoxides[16,17] proceed under neutral conditions without addition of bases. 

Allyl Carbamate (AII0C-NR2) CH2=CHCH20C(0)NR2 (Chart 8) Formation... 

Wlien an allylic carbamate b syn substitution occurs [ 54], For diliydroxy-16-ene-vitaniin D 165 9.16) [55], In route A, tlie CD side cli S 2 syn substitution of allylic... 

Cuprates react rapidly witli allylic halides for acetates) [17, 23], propargyl halides for acetates) [ 106-108], and vinyloxiraties, often witli S 2 regioselectivity iSclieme 10.9) [17]. Hie reaction takes place witli emit stereodieniistry iwitli respect to tlie leaving group), while syn substitution occurs when an allylic carbamate is employed as tlie substrate [109]. 

An efficient kinetic resolution of racemic secondary allyl carbamates was accomplished by the jw-butyllithium-(-)-sparteine complex76 131. Whereas the R-enantiomer (80% ee) is recovered unchanged, the 5-enantiomer is deprotonated preferentially. 

Z)-3-Alkoxyallylstannanes of high optical purity are available by stannylation of lithiated allyl carbamates derived from optically active allyl alcohols118. 

The addition of titanated allyl carbamates to jV-protectcd (S )-amino aldehydes allows rapid access to intermediates for various dipeptide isosteres98-10°, offering a versatile brick-box system (Table 5). If an acidic amino group is present, two equivalents of reagent are required. 

Remarkable y-syn-substitution preference is observed in the reaction of allylic carbamates with organocuprates. 

Lithiated allylic carbamates (35) (prepared as shown) react with aldehydes or ketones (R C0R ), in a reaction accompanied by an allylic rearrangement, to give (after hydrolysis) y-hydroxy aldehydes or ketones. The reaction is called the homoaldol reaction, since the product is a homolog of the product... 

Allyl carbamates also can serve as amino-protecting groups. The allyloxy group is removed by Pd-catalyzed reduction or nucleophilic substitution. These reactions involve formation of the carbamic acid by oxidative addition to the palladium. The allyl-palladium species is reductively cleaved by stannanes,221 phenylsilane,222 formic acid,223 and NaBH4,224 which convert the allyl group to propene. Reagents... 

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. 

A second route to nonracemic /-oxygenated allylic stannanes utilizes an enantioselective deprotonation of allylic carbamates by BuLi in the presence of (—)-sparteine. The configurationally stable a-lithio carbamate intermediate undergoes enantioselective S/,-2 reaction with Bu3SnCl and Mc SnCI (Scheme 28)65. Once formed, the /-carbamoyloxy stannanes can be inverted by successive lithiation with. s-BuLi and stannation with R3SnCl (Scheme 29)65. The former reaction proceeds with S/.-2 retention and the latter by Sf2 inversion. Nonracemic allylic carbamates can also be used to prepare chiral stannanes. Deprotonation with. s-BuLi TMEDA proceeds stereospecifically with retention (Scheme 29)65. 

Titanated allyl carbamates are reported to react regio- and stereospecifically with aldehydes [52]. An elegant and synthetically useful method based on diastereoselective and en-antioselective homoaldol reactions has been developed (Scheme 13.25) [53]. 

Scheme 13.25. Diastereoselective and enantioselective homoaldol reactions using titanated allyl carbamates.

Carbamate glycosyl donors are another useful class of compounds, which pre sent significant variability in chemical structures (Scheme 3.24). In an early example by Kunz and Zimmer, the N-allyl carbamate donors were used in a remote activation protocol to furnish pyranoside and furanoside products. In this reaction, the N-allyl carbamate donor 146 is activated with dimethyl methylthiosulfonium... 

Scheme 3.27. Regioselectivity in reactions of silyllithium and silyl cuprate reagents with allylic carbamates and epoxides...

High levels of asymmetric induction can be achieved intramolecularly if the substrate functionality and the heteroatom ligand are contained in the same molecule. Chiral amido(a]kyl)cuprates derived from allylic carbamates [(RCH= CHCH20C(0)NR )CuR undergo intramolecular allylic rearrangements with excellent enantioselectivities (R = Me, n-Bu, Ph 82-95% ee) [216]. Similarly, chiral alkoxy(alkyl)cuprates (R OCuRLi) derived from enoates prepared from the unsaturated acids and trans-l,2-cyclohexanediol undergo intramolecular conjugate additions with excellent diasteroselectivities (90% ds) [217]. 

Scheme 6.38. Influence of reagent and alkene geomet7 on allylic substitution of y-silyl-substituted allylic carbamates 181 (Ts = para-toluenesulfonyl, NMP = N-methylpyrrolidinone).

Scheme 6.39. Interpretation of the results of all of y-silyl-substituted allylic carbamates.

Scheme 8.4. Employment of allylic carbamates 1 in cop per-mediated asymmetric substitution.

Scheme 8.S. Optimized reaction conditions for reactions between allylic carbamate 1 (R = 1-naphthyl, X = OMe) and organocopper reagents R"Cu.

Allylic substitution with free carbamate nucleophiles was not accomplished until advanced catalyst precursors were developed. However, products from substitution with carbamate nucleophiles were generated by a decarboxylative allylation. In this process, the imidodicarbonate was shown to undergo decarboxylation to form the carbamate nucleophile, and reaction of the resulting carbamate with the 7i-allyliridium intermediate formed branched allylic carbamate products (Scheme 17) [92, 95]. 

---