Reaction with allene derivatives

An interesting annelation reaction of allene-derived 13-dipoles with 3-(IV-aryliminomethyl)chromones 38 affords, in fair yields, after [4 +3] cycloaddition and a subsequent cascade of rearrangements, derivatives of the novel iV-aryl-2,3-dihydro-4-ethoxycarbonylchromano[2,3-h]azepin-6-one system 39 (for example, R = Me, R1 = Cl) (Scheme 9). In the initial cycloaddition, the substituted chromone acts as an azadiene moiety <00OL2023>... 

The reaction of allene derivatives with Simmons-Smith reagent gives mono- and dimethylenated products 30, 31, 34, 405, 518, 530). 

S,3,)-(EBIH)Zr(=NAr)(THF)2 promotes highly enantioselective cycloaddition reactions with allenes and, in certain cases, this system allows conversion of an allene racemate into a mixture enriched in one enantiomer. Mechanistic studies about the enantioselective cycloaddition and stereoinversion of allenes mediated by imidozirconocenes have revealed that the initial [2 + 2]-cycloaddition to form the azazirconacyclobutane is stereospecific and is not involved in the racemization process.728 The reactive zirconocene imido precursor r -(EBIH)Zr(NHBut)(Me) 958 has been shown to activate a variety of hydrocarbons R-H with primary alkyl, alkenyl, and aryl G-H bonds to form the corresponding alkyl derivative r -(EBIH)Zr(NHBut)(R) 959 with concomitant elimination of methane729 (Scheme 240). Mechanistic experiments support the proposal of intramolecular elimination of methane followed by hydrocarbon G-H addition. 

A number of cycloaddition reactions involving allene derivatives as dienophiles have been recorded. Allene itself reacts only with electron-deficient dienes but allene carboxylic acid or esters, in which a double bond is activated by conjugation with the carboxylic group, react readily with cyclopentadiene to give 1 1 adducts in excellent yield. For example, the allene 12 gave, with very high yield and selectivity, the cycloadduct 13, used in a synthesis of (-)-P-santalene (3.19). An allene equivalent is vinyl triphenylphosphonium bromide, which is reported to react with a number of dienes to form cyclic phosphonium salts. These can be converted into methylene compounds by the usual Wittig reaction procedure (3.20). 

The reaction of allenic derivatives, tetraalkyldiphosphine disulfide and camphorsulfonic acid gave E-2-dialkylthiophosphinoyl-2-alkenes in the presence of RhH(PPh3)4. The reaction involved the P-P cleavage and the transfer of the thiophosphinoyl group to the allenic species with the simultaneous formation of thiophosphinic anhydride (Scheme 19). ... 

C(H)Me] complex. Protonation of (139) yields cationic vinyl complexes of structure (140), which on reduction with BH4 also yield the bridged carbene derivatives Cp2M2(CO)3[(M-C(H)Me]. The latter react further with alkynes under irradiation to give complexes of structure (141). Diphenylacetylene may be displaced thermally from (139 R = Ph, M=Ru) on reaction with allene to give (142), isomeric with (141). Protonation of (142) yields a vinyl derivative of structure (140), which may be reduced with BH4- to give the carbene complex... 

When allene derivatives are treated with aryl halides in the presence of Pd(0), the aryl group is introduced to the central carbon by insertion of one of the allenic bonds to form the 7r-allylpalladium intermediate 271, which is attacked further by amine to give the allylic amine 272. A good ligand for the reaction is dppe[182]. Intramolecular reaction of the 7-aminoallene 273 affords the pyrrolidine derivative 274[183]. 

Other approaches to (36) make use of (37, R = CH ) and reaction with a tributylstannyl allene (60) or 3-siloxypentadiene (61). A chemicoen2ymatic synthesis for both thienamycia (2) and 1 -methyl analogues starts from the chiral monoester (38), derived by enzymatic hydrolysis of the dimethyl ester, and proceeding by way of the P-lactam (39, R = H or CH ) (62,63). (3)-Methyl-3-hydroxy-2-methylpropanoate [80657-57-4] (40), C H qO, has also been used as starting material for (36) (64), whereas 1,3-dipolar cycloaddition of a chiral nitrone with a crotonate ester affords the oxa2ohdine (41) which again can be converted to a suitable P-lactam precursor (65). 

Benzonitrile oxide reacted with 3-phenyl-4-benzylideneisoxazolinone to produce two isomeric spiro compounds (Scheme 153) (72MI41609,72MI41608). The reaction of benzonitrile oxide with ketene produced a spiro derivative (67MI41600) with allenes, bis(spiroisoxazo-lines) along with monoaddition products were formed (Scheme 154) (79JOC2796, 70CR(C)-(271)1468). 

The allene 149 gave by reaction with maleic anhydride (entry 1) and N-phenylmaleimide (entry 2) the [2 + 2] adducts 155a, b as mixtures of two diastereoisomers [36], Nevertheless, their chemical yield was very low and competitive reactions, mostly [4 + 2] cycloadditions on a rearranged al-lylidenecyclopropane and on a primary 1 1 adduct derived from an ene reaction (see Sect. 2.1.2), prevailed. Allenes 149 and 563 cycloadded to tetracyano- and l,l-bistrifluoromethyl-2,2-dicyanoethylene (Table 45, entries 3-6) also selectively at the cyclopropyl substituted double bond in order to remove most of the ring strain [149a],... 

In the presence of triphenylphosphine as a catalyst, benzotriazole adds readily to activated allenes. Its reaction with ethyl 2,3-butadienoate produces a mixture of adducts 149 (54%) and 150 (20%). Both derivatives form exclusively as (Tyi-isomers <2006T3710>. In a reaction of benzotriazole with dibenzoylacetylene and... 

In the reaction of 1 with alkynes possessing electron-withdrawing substituents, the corresponding silacyclopropene derivatives 66 and 67 are formed, as described in Scheme 23.29 An unexpected pathway was observed in the reaction with the electron-poor hexafluorobutyne(2) the X-ray characterized heterocycle 68 was most likely obtained by nucleophilic attack of 1 at the triple bond. A subsequent shift of a fluorine atom from carbon to silicon creates an allene-type molecule which was stabilized by a [2 + 2] cycloaddition process involving a double bond from the pentamethylcyclopentadienyl unit, as described in Scheme 24.33... 

Allenyl cations have been generated by solvolysis of allenic derivatives, by photolysis of allenyl halides and by reaction of metal salts with allenyl and propargyl halides. This review will delineate these reactions. The related butatrienyl cations are not many and they will be only briefly described. 

Carbon dioxide instead of aldehydes can be involved in Ni(0)-promoted reductive coupling reactions (Equations (76) and (77) Scheme 90).434,434a 434c A stoichiometric amount of Ni(COD)2/DBU reacts with C02 and dienes, alkynes, or allenes to afford a metallacycle intermediate. This metallacycle reacts with organozinc compounds or aldehydes in one-pot to give carboxylic acid derivatives. As shown in Scheme 90, double carboxylation occurs in the presence of dimethylzinc, where the stereochemical outcome is opposite to that of the reaction with diphenylzinc. 

The intramolecular cyclization of l,2-dien-7-ynes and l,2-dien-6-ynes regiospecifically affords the corresponding titanacycles, which react with protons, carbon monoxide, aldehydes, or imines to give single products, as shown in Eqs. 9.56 and 9.57 [102], As the formation of titanacycles and their subsequent reaction with externally added reagents such as carbon monoxide (Eq. 9.56) or an aldehyde (or imine) (Eq. 9.57) proceeds with excellent chirality transfer, this represents a new method for synthesizing optically active cyclopentane derivatives from optically active allenes [102]. 

The alternative building scheme C2 + Q was used by Petasis and Hu [89], who reacted various aldehydes and ketones with alkenyltitanocene derivatives 172 to obtain the corresponding allenes 173 in high chemical yields (Scheme 2.54). The reaction probably proceeds via titanocene vinylidene complexes, which can also be trapped with alkynes and isocyanides to afford allenylketene imines [90],... 

One of the most popular methods for the synthesis of allenes is the Sn2 reaction of propargylic derivatives with organocopper reagents [1, 2], Most probably a study published in 1968-69 by Rona and Crabbe represents the first example of the Cu(I)-mediated SN2 reaction of propargylic electrophiles giving allenic products (Scheme 3.32) [69, 70], Since then, many researchers have used modified organocopper reagents with stoichiometric or catalytic amounts of Cu(I) salt. 

Less common addition reactions such as the bromination of trifhioromethyl-substi-tuted butatrienes [30] or the reaction of tetrafluoroallene with boron trifluoride have also been reported [283]. Especially the interaction of phosphorylated allenes with electrophiles was summarized in a review by Alabugin and Brel [8], whereas Smadja [284] published a more general overview about the electrophilic addition to allenic derivatives. 

Saalfrank, Hoffmann and co-workers performed a number of reactions with tetra-alkoxyallenes such as 196 (Scheme 8.47) [1, 41, 105, 114—116] and demonstrated that this class of donor-substituted allenes can serve as a 1,3-dianion equivalent of malonic acid. Treatment of 196 with cyclopropyldicarboxylic acid dichloride 197 produces 2,4-dioxo-3,4-dihydro-2H-pyran 198 through release of two molecules of ethyl chloride [115]. Similarily, the reaction of this allene 196 with oxalyl chloride gives 3-chloromalonic acid anhydride derivative 199. This intermediate is a reactive dieno-phile which accepts 2,3-dimethyl-l,3-butadiene in a subsequent [4+2] cycloaddition to afford cycloadduct 200 in good yield [116]. 

An intramolecular Diels-Alder reaction of allenic dienamide 181 provided the tet-rahydroindole ring system 182, which was oxidized with DDQ or Mn02 to give indole derivatives [147]. 

The addition of allenyl ether-derived anions to Weinreb [4] or to morpholino amides [5] follows a slightly different pathway (Eq. 13.2). For example, the addition of lithioallene 6 to Weinreb amide 7 at -78 °C, followed by quenching the reaction with aqueous NaH2P04 and allowing the mixture to warm to room temperature leads to cyclopentenone 9 in 80% yield [6]. The presumed intermediate of this reaction, allenyl vinyl ketone 8, was not isolated, as it underwent cyclization to 9 spontaneously [7]. These are exceptionally mild conditions for a Nazarov reaction and are probably a reflection of the strain that is present in the allene function, and also the low barrier for approach of the sp and sp2 carbon atoms. What is also noteworthy is the marked kinetic preference for the formation of the Z-isomer of the exocyclic double bond in 9. Had the Nazarov cyclization of 8 been conducted with catalysis by strong acid, it is unlikely that the kinetic product would have been observed. 

A large number of reaction conditions have been defined for the rearrangement of various allene derivatives into small heterocycles. The rearrangements have been accomplished variously with acids, bases or oxidatively. 

In spite of these first successful results, so far Stille cross-couplings have rarely reported employing functionalized stannylated allenes such as easily available donor-substituted allene 80a or allenyl esters such as 81 (Scheme 14.19) [19, 41, 42]. A single palladium-catalyzed annulation reaction with 80b as precursor leading to an a-pyrone derivative was reported [43],... 

The proposed mechanism involves the usual oxidative addition of the aryl halide to the Pd(0) complex affording a Pd(II) intermediate (Ar-Pd-Hal), subsequent coordination of allene 8 and migratory insertion of the allene into the Pd-C bond to form the jt-allylpalladium(II) species 123. A remarkable C-C bond cleavage of 123 leads by decarbopalladation to 1,3-diene 120 and a-hydroxyalkylpalladium species 124. /8-H elimination of 124 affords aldehyde 121 and the H-Pd-Hal species, which delivers Pd(0) again by reaction with base (Scheme 14.29). The originally expected cyclization of intermediate 123 by employment of the internal nucleophilic hydroxyl group to form a pyran derivative 122 was observed in a single case only (Scheme 14.29). 

More attractive copper-catalyzed (mediated) transformations of allenes into alkynes were reported by Caporusso and co-workers [27f, 73-75], Allenes 142 were converted into alkynes 143 by treatment with stoichiometric amounts of a cuprate species, as exemplified in Scheme 14.35. The problem of regioselective formation of either alkyne 143 or allene 144 was solved by the proper choice of the organometallic species. Preferential formation of alkynes 143 could be achieved employing cuprates such as R3Cu(CN)ZnCl-LiCl, which are prepared from organozinc compounds. On the other hand, reactions of organomagnesium derived cuprates (R3CuBr)Mg-LiBr mostly provided allenes 144 as major components. 

A route involving trapping the enolate as a silyl enol ether, subsequent transme-tallation to the corresponding lithium enolate and alkylation turned out to be more efficient (Scheme 18.41) [123]. Thus, treatment of 120 with the cuprate 124 and chlorotrimethylsilane furnished the silyl enol ether 125, which was then converted into the desired enprostil derivative 127 with 68% yield over both steps by reaction with methyllithium and the allenic triflate 126. 

The benzannulated enyne-allenes 48 were likewise synthesized in situ from coupling between 41b and the bromoallene 47 (Scheme 20.11) [39]. Under the reaction conditions, 48 presumably underwent a spontaneous cation-mediated Myers-Saito cyclization reaction with a concomitant 1,2-shift of the trimethylsilyl group to give the naphthalene derivatives 49. 

Treatment of the propargylic alcohol 144, readily prepared from condensation between benzophenone (143) and the lithium acetylide 101, with thionyl chloride promoted a sequence of reactions with an initial formation of the chlorosulfite 145 followed by an SNi reaction to produce in situ the chlorinated and the benzannulated enyne-allene 146 (Scheme 20.30) [62], A spontaneous Schmittel cyclization then generated the biradical 147, which in turn underwent a radical-radical coupling to form the formal [4+ 2]-cycloaddition product 148 and subsequently, after a prototropic rearrangement, 149. The chloride 149 is prone to hydrolysis to give the corresponding 11 H-bcnzo h fluoren-ll-ol 150 in 85% overall yield from 144. Several other llff-benzo[fc]fluoren-ll-ols were likewise synthesized from benzophenone derivatives. 

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