Intramolecular cycloadditions alkynes

A key intermediate, 163, which possesses all but one chiral center of (+ )-brefeldin, has been prepared by the enantiocontrolled cycloaddition of the chiral fi,/3-unsaturated ester 162 to 154[107], Synthesis of phyllocladane skeleton 165 has been carried out by the Pd-catalyzed cycloaddition of the unsaturated diester 164 and cobalt-catalyzed cycloaddition of alkynes as key reactions[108]. Intramolecular cycloaddition to the vinylsulfone in 166 proceeds smoothly to give a mixture of the trans and cis isomers in a ratio of 2.4 1[109], Diastereocontrolled cycloaddition of the hindered vinylsulfone 167 affords a single stereoisomeric adduct, 168, which is used for the synthesis of the spirocarbocyclic ring of ginkgolide[l 10],... 

Intramolecular cycloadditions between cyclobutadiene and an oxygen-tethered unactivated alkene (alkyne) offers an attractive route to benzo[c]furans (Scheme 26, <96JA9196>). 

The Dotz benzannulation reaction, based on the alkyne cycloaddition to chromium carbene complexes, is the most important application of Fischer carbene complexes. Among the various Fischer carbene complexes, alkoxy and aminocarbene complexes of chromium undergo a novel inter- and intramolecular tandem alkyne insertion/ carbene annotation sequence to give 9H-carbazoles and nf/-benzo[fl]carbazoles. 

However, by considering models of the anti configured ylide (Fig. 3.18), it was concluded that the inclusion of a three-carbon tether forces the reactive centers to be too sterically constrained to suffer intramolecular cycloaddition with an alkyne dipolarophile. Conversely, the syn ylide is able to achieve the correct approach for such a process, despite the steric interaction with the phenyl ring. Extension of the interim chain by one methylene unit using 6-heptynal, introduced a greater degree of flexibility into the system, allowing for the formation of the expected diaster-eoisomers (Scheme 3.101). 

Kanematsu and co-workers devised a simple pathway to isobenzofurans and dihydroisobenzofurans starting with substituted furans of type 62. Treatment with strong base results in an alkyne-allene isomerization. Subsequent intramolecular cycloaddition, ring opening (probably oxygen lone-pair assisted), and acidic workup give 63. 

In constrast with intermolecular nitrone cycloadditions to alkynes and allenes, very little work has been done on the corresponding intramolecular cycloadditions. The bicyclic isoxazolidines (65a-b) were reported as products from reaction of an alkynone with methylhydroxylamine in ethanol.26b Presumably the initial strained bridgehead C—C double bond of the AMsoxazoline added ethanol under the reaction conditions. Cyclization of an allenyl ketone with methylhydroxylamine in ethanol solution also led to isoxazolidines (65a-b) as the major products and isoxazolidine (66) as a minor product.266 Thus, preferential cyclization to the internal C—-C double bond of the allene occurred followed by addition of ethanol to the exocyclic C—C double bond of the methyleneisoxazolidine intermediate. 

Intramolecular azide cycloaddition to an alkyne produces a triazole. Triazoles are typically much more stable than triazolines and are most often directly isolable. Thus, azide (213) cyclized in 89% yield to a triazole (Scheme 65).118 The azido enyne (214) presents an interesting case intramolecular cycloaddition... 

Dihydrofurans are valuable synthetic compounds. Nevertheless, little is known about intramolecular cycloaddition of carbonyl ylides to alkynes. In one example, alkynyl pyran-4-one (233) was cyclized to dihydrofuran (234 Scheme 69).128 Possibly this reaction proceeds via an oxidopyrylium ylide intermediate as shown. 

Cyclization of dienynes.1 This Ni(0) catalyst in combination with a triarylphos-phite, particularly tri-o-biphenyl phosphite, permits intramolecular cycloaddition at 25° of [4+2] dienynes, in which the diene and the alkyne are separated by 3- and 4-atom units. This reaction is a useful route to products containing a cyclohexadiene group, which are oxidized to an arene by DDQ. 

Treatment of the dihydroisoquinolinium salt 699 with Hiinig s base (/-PrzNEt) produces the corresponding azomethine ylide, which can undergo intramolecular cycloaddition with the tethered alkyne to afford the chro-meno[3,4- ]pyrrol-4(3//)-one 700 in high yield. Subsequent deprotection of the isopropyl protecting groups affords the marine natural product lamellarin K (Scheme 173) <1997CC2259>. 

An interesting example of an intramolecular cycloaddition reaction has been observed in the case of the mesoionic 1,3-dithiolone (97) which contains a non-activated alkyne in the same molecule. Thus, on heating (97) at 40-45 or 100 °C, the tricyclic thiophene derivative (99) is obtained via the non-isolable primary adduct (98) (81LA347). 

The reactivity and selectivity of cycloaddition can be considerably increased in intramolecular versions. The protocol was first demonstrated in the Diels-Alder reaction between anthrone 253416,417 and 4-hydroxy-2-butenoate mediated by phenylboronic acid (Equation (73)).418,419 Another method developed for the intramolecular cycloaddition is the synthesis of trienylboranes 256 by hydroboration of terminal alkynes (Equation (74)).419-422... 

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