Patai S., Rappoport Z. 2000 The chemistry of functional groups. The chemistry of dienes and polyenes. V. 2 / 0329 479

acetylenes 568a–e and 198 were more reactive than disubstituted acetylenes 568f–h. The reactions between diphenylacetylene (568g) and norbornadiene did not take place at room temperature. Bis(trimethylsilyl)acetylene (568h) did not react, not even on prolonged heating at 60 °C. Dimers of norbornadiene were obtained instead.

X

CO2Me +

(563)1,2-dichloroethane, ∆ Ni(COD)2/2PPh3

(163)

The possibility of asymmetric induction in these reactions was probed by adding chiral phosphine ligands to the cobalt complex. Brunner and colleagues333 found an ee of 98.4% for the adduct of norbornadiene and phenylacetylene using a cobalt complex based on the chiral bidentate phosphine NORPHOS (570). They extended their studies to include a variety of other bidentate phosphines and different acetylenes, reaching enantioselectivities of more than 99%334. Buono and coworkers335 obtained high enantioselectivities (up to 97% ee) using a cobalt(II) iodide complex and amino acid based chiral phosphine ligand 571. Chiral phosphine 572 induced an ee of 82% in the reaction of norbornadiene

with phenylacetylene, as reported by Lautens and coworkers327,336. The highest enantioselectivity (91% ee) with 1-hexyne was found when phosphine 573 was employed as the chiral ligand.

R1

P P

Ph2P PPh2

The regioselectivity in the reactions of 7-substituted norbornadienes with substituted acetylenes generally proved low. The reactions of 563 and 2-methoxynorbornadiene with 1-hexyne (198) did not proceed. With 2-trimethylsilylnorbornadiene (574), adducts 575 and 576 were obtained, albeit in low to moderate yields (equation 165). The best regioselectivity (575=576 D 92/8) was obtained when the reaction was performed at room

group338a. Furthermore, the CpCo(CO)2 complex proved inefficient in these reactions. When CpCo(C2H4 2 was used, however, the reactions proceeded well.

THF, ∆ CpCo(C2H4)2

(167)

O

MeO

(584)

Vollhardt and colleagues338b studied the regiochemistry in these cycloaddition reactions. When the ˛,ω-diynes had large substituents at both termini, the reaction with N-phenylsulfonylindole did not afford any adduct due to steric hindrance. When smaller substituents were present, the cycloaddition proceeded in such a way that the larger substituent was distant from the phenylsulfonamide moiety, as illustrated for the reaction of 585 with 586 (equation 168). Anti 587 and syn 588 were obtained in a 61 : 39 ratio.

A formal synthesis of -lycorane was accomplished by Vollhardt and colleagues by employing a [2 C 2 C 2] cycloaddition between enyne 589 and 568h (equation 169)344. The reaction afforded a mixture of syn and anti adducts 590 and 591 in a 80 : 20 ratio when the reaction was conducted at room temperature. When the reaction was conducted in refluxing 568h/THF (1 : 1, v/v), a syn:anti ratio of 60 : 40 was obtained. A small amount of [2 C 2] adduct 592 was also isolated. This product became the dominant product when the enamide double bond was substituted. The additional steric hindrance probably prevented the enamide double bond from participating in the cycloaddition reaction.

Vollhardt and colleagues also investigated the [2 C 2 C 2] cycloadditions of alkyne tethered furans 593a and thiophenes 593b with alkynes345. The reactions with 568h proceeded to generate the expected cycloadducts 594a and 594b (equation 170). These species,

however, underwent heterolytic ring opening in most cases and provided the rearranged compounds 595a and 595b through a series of ring-closure/ring-opening sequences.

Malacria and coworkers346 prepared phyllocladane and kaurane types of diterpenes by means of [3 C 2]/[2 C 2 C 2]/[4 C 2] cascade reaction sequences. A representative example of such a reaction sequence has been outlined in equation 171. The five-membered ring of 598 was built by a 1,3-dipolar cycloaddition between 596 and an all-carbon 1,3-dipole generated from 597. The reaction of 598b with 568h afforded benzocyclobutene 599. The intramolecular [4 C 2] cycloaddition afforded diastereomers 600 and 601 in a 5 : 1 ratio. It is noteworthy that the exocyclic double bond in 598b neither participates in the [2 C 2 C 2] cycloaddition reaction nor isomerizes under the reaction conditions applied.

The kaurane type of adduct 601 became the major product when the methylene group at C(12) was replaced by a carbonyl group and substituents were present at C(15). Repulsive steric interactions between the substituents at C(15) and H(1) prevented the formation of phyllocladane type of compounds like 600347.

In a similar way, Malacria and colleagues accomplished the formation of the stemodan skeleton by a tandem [2 C 2 C 2]/[4 C 2] cycloaddition process348.

Apart from cobalt, other metals have also been shown to be able to catalyze [2 C 2 C 2] cycloaddition reactions. Grigg and coworkers349, for example, used a Pd(0) complex to catalyze [2 C 2 C 2] cycloadditions.

Tsuda and coworkers350 used nickel(0) complexes to effect the [2 C 2 C 2] cycloadditions between two alkyne units and one alkene unit and employed this strategy to synthesize copolymers. Thus, the reaction of diyne 602 with N-octylmaleimide (603) catalyzed by Ni CO 2 PPh3 2 afforded copolymer 604 with a maximum yield of 60% and a GPC molecular weight of as high as 35,000, which corresponds to n D 64 (equation 172). The exo,exo-bicyclo[2.2.2]oct-7-ene moiety of 604 arises through the reaction of the initially formed [2 C 2 C 2] adduct with another equivalent of N-octylmaleimide.

reacts with zinc to afford a Ni(0) species and zinc dichloride. The best catalytic results were obtained when 1.5 equivalents of zinc dichloride and triethylamine were added to the reaction mixture. Thus, methyl vinyl ketone (100) reacted with diyne 605 to afford the aromatized adduct 606 as the exclusive product (equation 173). The two abstracted hydrogen atoms proved to be incorporated into another molecule of methyl vinyl ketone.

When trimethylsilyl substituted diyne 607 was reacted with methyl vinyl ketone, the reaction proceeded with complete regioselectivity and without aromatization to afford 608 with 56% yield (equation 174). The regioselectivity observed was considered to result from a metallacyclopentene intermediate which was built up of the nickel atom, the double bond of methyl vinyl ketone and the less substituted triple bond of 607.

(170)

Rothwell and colleagues352 studied the titanium mediated [2 C 2 C 2] cycloaddition of alkenes with monoynes and diynes. Among the reactions studied, the reaction between styrene (29) and diyne 609 in the presence of titanium catalyst 610 proved cleanest (equation 175). The reaction yielded 614 via a [2 C 2 C 2] cycloaddition followed by a titanium mediated suprafacial [1,5] H-shift involving 611–613. The cis relationship between the trimethylsilyl group and the phenyl group indicated that the initially formed titananorbornene 611 had an endo stereochemistry.

The authors had evidence to believe that the addition of 29 to the titanacyclopentadiene complex proceeded in a Diels –Alder type of way, i.e. in a concerted manner instead of a stepwise manner via a titanacycloheptatriene intermediate.

Kotha and Brahmachary353 prepared some constrained ˛-amino acids using a rhodium mediated [2 C 2 C 2] cycloaddition reaction. The indane type of ˛-amino acids were synthesized by reacting diynes with monoynes using Wilkinson’s catalyst354. Thus, the reaction of diyne 615 with 616 afforded ˛-amino acid derivative 617 (equation 176).