Ene-allenes, cyclization

Ether was a better solvent in cases where the propargylic position was unsubstituted (methylene group) since, in THF, a competitive [1,2] -Wittig rearrangement took place and led to diminished yields. When applied to the secondary homoallylic propargyl ethers 388, the zinc-ene-allene cyclization afforded the c -2,3,5-trisubstituted tetrahydrofurans 389 with moderate to satisfactory levels of diastereoselectivity, which could be rationalized by the preferential pseudo-equatorial positioning of the homoallylic substituent in the cyclic... 

The synthesis of polysubstituted pyrrolidines has been achieved344 in a diastereo-selective and enantioselective manner via the zinca-ene-allene cyclization. In an extension of this work,345 the zinca-ene-allene reaction of polysubstituted enynes lithiated on the propargylic position has been used to prepare polysubstituted... 

A nickel-chromium catalyst prepared from chromous chloride and (p-diphenylphos-phinopolystyrene)nickel dichloride mediates the ring-closure of the ene-allene 236 (R = H) to a mixture of 3.4 parts of 237 and 1 part of 238 (equation 120)121. An analogous reaction of the t-butyldimethylsilyl ether of 236 yields solely the (E)-isomer 237 (R = t-BuMeaSi). Cyclization of the ene-allene 239 affords the perhydroindane 240 in 72%... 

PtCl2 was shown to catalyze a similar Alder-ene transformation, as in the cycloisomerization of allenyne 117 to triene 118 (Equation (76)).78 In the same study, it was noticed that tetrasubstituted allenes cyclized to bicyclic compounds, such as 120 (Scheme 23), under identical PtCl2 conditions, presumably due to A(1,3) strain in intermediate 119. 

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. 

Singleton and coworkers took up the ene cyclization reaction of ene-allene (Scheme 4) and carried out combined experimental-computational investigation.43 The ene reaction had been known to show mechanistic uncertainty, in particular whether it proceeds via a concerted or stepwise route, and therefore provided a challenge for dynamics study. KIE measurement for the reaction of 22 (Ri = R.2 = TMS) in toluene at 50°C gave kcus/kcm of 1.43, which was smaller than what was normally observed in concerted ene reactions. However, the isotope effect was too large to support a stepwise ene reaction. Thus, this was in line with the idea that the mechanism is near the concerted-stepwise borderline. 

Singleton carried out a combined experimental/computational/MD study of the enyne-allene cyclization problem. First, he determined that the experimental KIE for the cyclization of 60 is 1.43. This value is smaller than that usually found for concerted ene reactions, where kg/kjj is often greater than... 

Another facet of the cyclization of secondary organometallic derivatives is the use of d-ethenic allylmetals [61] this has been abundantly reviewed [58] and is considered as a metallo-ene reaction. However, although the ene-allene reaction was disclosed 10 years ago [59] to interpret the formation of a cyclic product by flash pyrolysis of a 2,3,8-nonatriene, the corresponding metallo-ene-allene reaction has received attention only veiy recently in organic synthesis [60]. 

The first approach is triggering through the ene-allene rearrangement caused by decarboxylation of methoxymalonate terminating one acetylene branch of enediyne. An enediyne model 3.744 in basic medium produces enyne-allene 3.745. The latter undergoes the Myers-Saito cyclization and generates toluic diradicals 3.746 and through a cascade... 

Weinreb86 has reported the Alder-ene cyclization of enallenes under thermal conditions (Equation (85)). Varying the substitution pattern of alkene and allene groups had little effect on the yield of cyclized product. One exception was a,/ -unsaturated ester 130(Equation (86)) cycloisomerization under thermal conditions led to the formation of the Alder-ene product 131 and the unexpected hetero-Diels-Alder product 132 in a 3 1 ratio. 

Product stabilization is much more pronounced when the enediyne or ene-yne-allene starting materials are not already part of an aromatic system, since forming an aromatic system constitutes a much higher degree of stabilization than expanding an aromatic system (Fig. 24). Conjugation of the radical center provides additional stabilization to the 71-radical formed by the Myers-Saito and Schmittel cyclizations. 

Wang s approach for the synthesis of enyne-allenes focused on ene-allenyl iodide 45 (Scheme 14.12) [24]. Palladium-catalyzed Sonogashira reaction of 45 with terminal alkynes 46 (R= Ph or CH2OH) proceeded smoothly under mild reaction conditions in the presence of the cocatalyst cuprous iodide and n-butylamine. The initially formed enyne-allene 47b with substituent R= CH2OH cyclized spontaneously to the corresponding a-methylstyrene derivative 48. 

---