Allenes intramolecular cyclizations

Table 10-6. Intramolecular cyclization of compounds with the general structure 10.41 (after Saunders and Allen, 1985).

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]. 

Pyrrolo[l,2- ][l,2]oxazines are a class of compounds with very few references regarding synthesis and reactivity. An interesting preparation has been described by intramolecular cyclization of IV-hydroxy pyrrolidines carrying a methoxyallene substituent at C-2 (242, Scheme 32). These compounds were obtained by addition of a lithiated allene to chiral cyclic nitrones 241. Cyclization occurred spontaneously after some days at relatively high dilution (0.05 M). Compounds 243 (obtained with excellent diastereoselectivity) can be submitted to further elaboration of the double bond or to hydrogenolysis of the N-O bond to form chiral pyrrolidine derivatives (Section 11.11.6.1) <2003EJ01153>. 

Several routes to the pyrrolo[l,2-f][l,2,3]triazole skeleton have been described. Intramolecular dipolar cycloaddition of azido-alkenes or alkynes seems to be the most convenient process, although the cyclization efficiency seems to be highly substrate dependent (Scheme 16) <2002JA2134, 2003T1477, 2005SL2187, 2005TL8639>. The formation of this bicyclic system by an intramolecular Heck reaction is an attractive alternative. The recent syntheses of sulfamides by intramolecular cyclization of alkenes or allenes offer a complementary route to the classical... 

Efforts have been made to find stereoselective routes which provide disubstituted azetidines. Palladium catalysed cyclization of an enantiomer of allene-substituted amines and amino acids gives the azetidine ester 2 and a tetrahydropyridine in variable yield and ratio, depending on the substituents and conditions <990L717>. The (TRIS)- and (253I )-isomeis of the substituted azetidine-2-carboxylic acids 3 (R = COjH) are obtained in several steps from the corresponding 3 (R = CHjOSiMejBu ) which, in turn, is produced in high yield by photochemical intramolecular cyclization <98HCA1803>. 

A few synthetic applications of palladium catalysis appeared this year. The palladium-catalyzed cyclization of amino allenes 58 occurs with coupling of aryl iodides or vinyl triflates at the 3-position <990L717, 99SL324>. The cyclization can also proceed by the exo-trig pathway, but under suitable reaction conditions the piperidine 59 is prepared selectively. The intramolecular cyclization of amines onto N-allylbenzotriazoles similarly affords piperidines <99JOC6066>. 

The perfect diastereoselectivity observed in these reactions lead to the assumption that they do not proceed via a simple anionic intramolecular cyclization (i.e. carbozincation) as was proposed in earlier61 publications. Cyclizations of non-propargylic substrates15,62 were shown to proceed with significantly lower diastereoselectivity (cis/trans typically 75/25). Thus, in the case of propargylic compounds, e.g. 114, a simple carbozincation process is unlikely to be operative. It was therefore reasoned that the active species in these reactions is not 115-ZnBr but rather its allenic isomer 120, which undergoes a metallo-ene-allene reaction in a chair-like transition state as depicted in equation 5659a. 

The propargylsilane group can participate in intramolecular cyclization reactions to give a five-membered ring with an exocyclic allene group. An example is the cyclization of 2 to a mixture of 3 and 4 when treated with acetic acid. 1... 

The tandem radical cyclization of tetrayne (97) and its derivatives has been performed to generate the polycyclic pyran (98) via a biradical intermediate.238 The cycloaddition reaction of a biradical species (or diyl) and a multiply bonded species (the diylophile)239 has been observed with unique allene diylophiles.240 The short-lived biradical fonned by the irradiation of the diazene (99) is trapped by an allene diester to form a second biradical species (100). Intramolecular cyclization occurs such that all steric interactions are minimized and so enforces stereocontrol in the formation of the cycloadduct (101) see Scheme 14. A paper reports the rearrangement of 2-vinyhnethylenecyclopropane (102) to 3-methylcyclopentene (103) via the triplet biradical (104), which has been characterized for the first tune by IR spectroscopy.241... 

Richey, H. G. Kossa, W. C. Intramolecular cyclization of an allenic Grignard reagent. Tetrahedron Lett. 1969, 2313—2314. 

Stereocontrolled conjugate addition of lithium dimethylcuprate to the electron deficient 2,3-double bond of allenes 851 leads to 5,6-dihydropyranM-oncs 852 in moderate yield (Equation 343) <2000J(P1)3188>. Similarly, the Ag(l)-catalyzed intramolecular cyclization of the allenic acid 853 is accelerated upon addition of diisopropylethyl-amine to afford the 3,6-dihydropyran-2-one 854, an intermediate during the total synthesis of (—)-malyngolide (Equation 344) <2000JA10470>. 

PyrroUvdines (11, 546). Intramolecular cyclization of an a-acylamino radical to an allene provides a route to the pyrrolizidine alkaloid supinidine (4), outlined in Scheme (1). 

Intramolecular allene alkyne cyclizations using cobalt complexes are nonspecific and both double bonds of the allene participate in the reaction affording [4.3.0] and [3.3.0]ring systems (Scheme 260). Both inter- and intramolecnlar Pauson - Khand-type reactions have been reported using... 

Becker and his co-workers have studied the intramolecular cyclization of allenes to enones (20). They propose that the first bond formed is by bonding at C-p of the enone via a biradical intermediate of the sort shown in (21), and... 

Heterocycles. The intramolecular cyclization of o-allylphenols to form 2//-l-benzopyrans and coupling of iodoalkenylamines and (o-iodoaryl)alkylamines with allenes to give azacyclic productsare useful preparative methods. 

Thus irradiation of ethyl 2-cyano-4-methyl-l,2-dihydroquinoline-l-carboxylate (3a) in diethyl ether with a 350-W high-pressure mercury lamp through a Pyrex filter gave a cyclopropaindole as minor product, along with ethyl 2-cyanomethyl-3-methylindole-l-carboxylate arising from the intramolecular cyclization of an allene intermediate. 

Some thermal cyclization reactions of allene derivatives in their own crystals are described. Intramolecular cyclization of diallene derivatives within their crystals proceeds stereoselectively according to the Woodward-Hoffmann rule. For example, heating of colorless crystals of meso- 19 and rac-diallene 23 at 150 °C for 1 h gave the in,out 22 and a 1 1 mixture of in,in 26 and out,out 27 cyclization products, respectively, in quantitative yields (Scheme 2.2.1) [14]. Since no liquid state was observed during the cyclization reactions, the reaction in the crystal is a real crystal-to-crystal reaction. An X-ray analysis showed that 19 and 23 have an s-trans configuration in the crystal [15], In order to cyclize to 22, and to 26 and 27, 19 and 23 should first isomerize to their s-cis-isomers 20 and 24, respectively, in the crystal. The conformational change, from the s-trans form to the s-cis form, requires... 

The usual ring-size dependence for cyclization was noted. Dehydrohalogenation to the terminal olefin was observed in attempted preparation of cyclobutanes. The allene isomer in favorable cases also undergoes intramolecular cyclization ... 

Carbonyl couplings. Many variations of cross couplings are possible these include aldehydes with a-dicarbonyl compounds. Ketyl radicals derived from carbonyl compounds also add to alkenes such as acrylonitrile " or N-allyl moieties. Intramolecular cyclizations on terminal alkenes or allene species have also been exploited for synthetic purposes. 

In 2006, Krause and Nakamura independently reported the first examples of Au-catalyzed transformations of sulfur-containing reagents [11, 247]. These reports are particularly notable, as they dispel the myth of sulfur-gold incompatibility. Krause s approach involves intramolecular cyclization of a thiol onto an allene... 

The allenic oxime (135) undergoes a silver-catalyzed cyclization to form the nitrone (136) (Equation (10)) which may be trapped as the dipolar adduct (137) with vV-methylmaleimide <91JCS(Pl)659>. Azepinonitrones have also been prepared by the spontaneous intramolecular cyclization of alky-nylhydroxylamines, prepared by the reduction of the corresponding oximes <92TL742l, 92TL7425>. 

Intramolecular cyclization of (76) in the presence of NaH gave exo (77) and endo (78) products (Equation (9)) <90SL584). Allene-based electrophile-mediated cyclization afforded iV-tosyl iodohexa-hydroazocines <94JCS(Pl)3549>. Photochemical intramolecular cycloaddition of phthalimide in acetone afforded the ring-opened product <82TL498l>. An unstable enaminone azocine derivative (81) was formed after the desulfurization of the bicyclic aminal (80), which in turn was synthesized from... 

These authors found (Scheme 52), that treatment of allene 341 with a variety of palladium(II) reagents gave only traces of the corresponding A -carbapenem system. However, when the intramolecular cyclization was carried out in the presence of allyl compounds, the carbapenem system 342 was formed in moderate yield. This procedure constitutes a tactically novel organotransition metal approach to A - and A -carbapenems. 

A number of reports concern the attack of nucleophiles on perfluoro-olefins to give cumulenes or heterocumulenes, which in turn imdergo nucleophilic attack to give heterocyclic compounds with perfluoroalkyi substituents. o-Phenylenedi-amine reacts with hexafluoropropene to give 2-(o j8j8>tetrafluoroethyl)benzimidazole (301) ketenimine intermediates have also been utilized in the formation of quinolines (302) (see p. lll) 89.59o j,y intramolecular cyclization, and (303) (see p. 112) by intermolecular cyclization, naphthyridines (304), pyridopyrimidines (305), and isoquinolines (306). The pyran derivative (307) is formed via isomerization of an allene intermediate (see p. 100). 3-Fluoro-2-isopropyl-l,2,4-thiadiazolin-... 

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