Dienes, reaction with isocyanates

Cycloaddition Reactions. In [2+2] cycloaddition reactions with car-bodiimides sometimes [2+4] cycloadducts are produced as coproducts. Examples include the reaction of phenylcarbonyl isocyanate, phenylcarbonyl isothiocyanate and thiocarbamoyl isothiocyanate with carbodiimides to give [2+4] cycloadducts, discussed in Section 5.3.1. In the current section, mainly [2+4] cycloaddition of carbodiimides as dienophile with dienes derived from oxoketenes, generated in situ or masked oxoketenes, especially 2,3-diones investigated by Kollenz and his coworkers are discussed. 

Acyl isocyanates are more reactive than alkyl or aryl isocyanates. However, the presence of an additional rr-bond conjugated to the C>i-N bond of the isocyanate opens the possibility for [4 + 2] cycloadditions to compete with normal [2 + 2] additions. Reactions with alkyl and aryl substituted alkenes are rather slow. Propene, tranj-2-butene, styrene and conjugated dienes give only 3-lactams, albeit in moderate yields (Scheme 25). The strained double bond of norbomene, a reactive dienophile, adds across the conjugated 4iT-system of trichloroacetyl isocyanate (equation 51). 

The first total synthesis of ( )-lycoridine margetine (33), a member of the non-basic alkaloids which possess antimitotic activity has been achieved (Scheme 3). The homoallylic alcohol (26) served as a latent diene in a Diels-Alder reaction with ethyl acrylate to give a diastereomeric mixture of adducts which upon base equilibration and hydrolysis provided the tmns-acid (27). Modified Curtius reaction on (27) afforded the corresponding isocyanate which was cyclized to the lactam (28) in 89% yield by a new method using boron trifluoride etherate. Compound (28) was converted into an N-acetyl derivative which upon basic hydrolysis gave the acid (29). Treatment of (29) with NBS followed by reflux in pyridine solution gave the lactone... 

It is of interest that the reaction of alkynes with isocyanates in the presence of bis(cyclo-octa-1,5-diene)nickel(0) and tricyclohexylphosphine... 

Menthol [(—)-l] has been used as a chiral ligand for aluminum in Lewis acid catalyzed Diels-Alder reactions with surprising success2 (Section D.l.6.1.1.1.2.2.1). The major part of its application is as a chiral auxiliary, by the formation of esters or ethers. Esters with carboxylic acids may be formed by any convenient esterification technique. Esters with saturated carboxylic acids have been used for the formation of enolates by deprotonation and subsequent addition or alkylation reactions (Sections D.l.1.1.3.1. and D.l.5.2.3.), and with unsaturated acids as chiral dienes or dienophiles in Diels-Alder reactions (Section D. 1.6.1.1.1.), as chiral dipolarophiles in 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), as chiral partners in /(-lactam formation by [2 + 2] cycloaddition with chlorosulfonyl isocyanate (SectionD.l.6.1.3.), as sources for chiral alkenes in cyclopropanations (Section D.l.6.1.5.). and in the synthesis of chiral allenes (Section B.I.). Several esters have also been prepared by indirect techniques, e.g.,... 

Reaction with strained olefins. Monsanto chemists reported a few years ago that this isocyanate reacts with norbornene (1) in refluxing toluene (b.p. 110°) to form a 1 1 adduct (2) that is, the isocyanate behaves as a Diels-Alder diene under these conditions. More recently, Agosta et al. found that if this reaction is carried out in refluxing p-xylenc (b.p. 138°) the ,P-unsaturated carbonitrile (3) is obtained in high yield and that (2) cannot be converted into (3) under the same conditions. They suggest (hat (3) is formed via a [2 + 21-adduct (a). 

Even strain-free 2-vinylpyrrolidine can be cleaved by Pd to generate the ir-allylpalladium intermediate, and the l,3-diazepin-2-one 248a was obtained by the reaction with phenyl isocyanate as shown by 248. The use of Pd2(dba)3 and DPPP is important. When Pd(OAc)2 and PPha were used, conjugated diene was obtained by elimination [91]. 

Many examples of alkene and alkyne insertion into metal-carbon bonds can also be found in the section on homogeneous catalysis. Other recent examples include the insertion of conjugated dienes into palladium-allyl bonds, olefin arylation in the presence of palladium acetate, and the reaction of ethylene with arylmagnesium halides in the presence of nickel chloride. Reaction of isocyanates with nickel-ethynyl compounds... 

Just as alkenes can be condensed with isocyanates, one alkene unit of a diene can also react, eventually leading to an alkenyl amino acid. The condensation of CSI and 1,3-pentadiene in reaction 4 is one example and it gave 2.J02.51 Removal of the sulfonyl group and hydrolysis gave methyl 3-aminohex-4-enoate (2.55),51c a synthetic intermediate for the preparation of daunosamine.51a.c Similar reaction with 1,3-... 

The alkoxy dienes (6) containing a chiral carbohydrate auxiliary each undergo a highly stereoselective Diels-Alder reaction with naphthoquinone affording adducts (7). The vinyl ether (8), on treatment with tosyl isocyanate, stereoselectively produced the -lactam derivative (9). ... 

The reaction of isocyanates with suitable substrates also afford [3+2] and [4+2] cycloadducts. In [4+2] cycloaddition reactions the isocyanates usually participate as dienophiles. However, acyl-, thioacyl- and imidoyl isocyanates often participate as dienes in [4+2] cycloaddition reactions. In this manner numerous heterocyclic five- or six-membered ring compounds, respectively, are obtained. The 1,4-dipolar substrates can also be generated in situ using suitable catalysts. 

Cycloadditions Isocyanates undergo [4+2] cycloaddition reactions with 1,3-dienes, heterodienes, conjugated azomethines and cumulenes. The reactions generally proceed by addition across the C=N bond of the isocyanate, but additions across the C=0 bond are also known. 

In o-quinodimethane derivatives the dienes are in the c -configuration, which allows ready cycloaddition reactions with phenyl isocyanate. For example, phenylimines of o-quinodimethanes 461 afford the quinazolinediones 462 on reaction with phenyl isocyanate followed by hydrolysis... 

Likewise, imidoyl ketenimines 153 react as 1-aza-1,3-dienes in [4-1-2] cycloaddition reactions with phenyl isocyanate to give the cycloadducts 154 (62-67 % yields) or with tosyl isothiocyanate to give the cycloadducts 155 (62-69 % yields) . ... 

In 2005, Xi and coworkers reported that 1,1-cycloaddition of oxalyl chloride with l,4-dilithio-l,3-dienes 379 or zirconcyclopentadienes 397 afford CPDNs 399 in the presence of CuCl (Scheme 6.100a), in which the carbon-carbon bond of the 1,2-dicarbonyl component cleaves during nucleophilic addition [239]. They also found that no reaction is observed when 397 is treated with isocyanates. However, multiply substituted ICPDs 400 are formed from Lewis acid-promoted reactions (BF3-Et20) by a one-pot three-component coupling process (Scheme 6.100b) [240]. 

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