Diels-Alder reactions of vinylallenes

The Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

Murakami and colleagues132 studied the Diels-Alder reactions of vinylallenes with alkynes catalyzed by a rhodium complex. When a vinylallene lacking substituents at the vinylic terminus was reacted with a terminal alkyne, 1,3,5-trisubstituted benzenes were obtained, the reaction between vinylallene 197 and 1-hexyne (198) being a representative example (equation 55). The reaction was proposed to proceed via a rhodacycle which afforded the primary Diels-Alder adduct via reductive elimination. Aromatization via isomerization of the exocyclic double bond led to the isolation of 199. 

Spino and colleagues134 studied the Diels-Alder reactions of vinylallenes aiming to synthesize six-membered rings with a tetrasubstituted exocyclic double bond, which were to be employed as precursors of quassinoids. Some representative results of their investigations have been summarized in Table 5 (equation 56). Due to the presence of two different substituents at the allene terminus of 200, facial differentiation occurred, which resulted in non-equivalent amounts of geometrical isomers 201 and 202. The major isomers obtained in each case were formed by endo attack of maleic anhydride 144 at the less hindered face of the diene. 

Ab initio and DFT calculations of the Diels-Alder reactions of vinylallene and diallene with dipolarophiles show that these reactions are concerted processes and that cumulated dienes are less reactive than non-cumulated dienes.153 Electron-rich... 

MO calculations show that the diradical stepwise pathways are preferred over the concerted paths in the Diels-Alder cycloaddition of strained allenes, such as cyclohexa-1,2-diene, with cyclobuta-l,3-diene. An ab initio study of the regio- and stereo-selectivity of the Diels-Alder reaction of vinylallenes and methyl-substituted vinylallenes with acrolein showed the reactions to be asynchronous. Allenamides undergo inverse-electron-demand 4 - - 2-cycloaddition with alkyl vinyl ketones to yield pyranyl ketones. The cycloaddition of (silyloxyvinyl)cyclohexene (147) with the allenecarboxylate (148) produced the exo-cycloadduct (149), which is a key intermediate in the total synthesis of the phosphatase inhibitor dysidiolide (Scheme 57). ... 

Based on the facile formation and reactivity of 323, and the retro Diels-Alder reaction of 325306,310 a simple procedure has been developed for the stereoselective synthesis of functionalized conjugated dienes as well as vinylallenes (see equation 119). 

In 1988 Gibbs and Okamura [128] described the intramolecular Diels-Alder reaction of the non-racemic vinylallene 150 to afford the adduct 151 (as a mixture of epimers at sulfur) in a completely exo-selective manner, due to the topographical and steric arrangement of the starting vinylallene (Scheme 74). Compound 150 was obtained as a mixture of epimers at sulfur from the optically pure propargylic alcohol 149 (this transformation involved a sulfoxide-sulfenate rearrangement). Compound 151 was used to synthesize (-l-)-sterpurene. 

Okamura W. H., Curtin M. L. Pericyclization of Vinylallenes in Organic Synthesis on the Intramolecnlar Diels-Alder Reaction Synlett 1990 1 9... 

Further examples of the use of the hDA reaction in dihydropyran synthesis include the formation of the fused pyrans 18 from vinylallenes 17 and aldehydes (Scheme 8) <00TL6781> and a trans-fused dihydropyran containing a phosphonate group 19 . A total synthesis of the 11-oxa steroid system is based on an intramolecular Diels-Alder reaction involving an orthoquinodimethane derived from a benzocyclobutene (Scheme 9) <00TL1767>. 

The use of vinylallenes as the diene component in Diels-Alder reactions is very common, thus resulting in their ubiquitous use in natural product synthesis. A vinylal-lene has even been proposed by Schreiber and Kiessling [10] as a biogenetic intermediate in the synthesis of the skeleton of esperamicin A (32 —> 33). Their synthetic approach to esperamicin A (34) was modeled after this biogenetic proposal in which a Type II intramolecular Diels-Alder cycloaddition was used to gain access to the highly unsaturated bicyclic core of 34 (Scheme 19.8) [10]. 

A well-designed synthesis of the bottom portion of (+)-compactin (44) was reported by Keck and Kachensky using a vinylallene as the diene in an intramolecular Diels-Alder reaction (Scheme 19.10) [12]. This was done at a time when there was very little literature precedent on the use of vinylallenes as dienes. Based on examination of molecular models, it was reasoned that the transition state for the... 

Highly enantioselective 1,5-substitution reactions of enyne acetates are also possible under carefully controlled conditions (Eq. 4.31) [46]. For example, treatment of enantiomerically pure substrate 70 with the cyano-Gilman reagent tBu2CuLi-LiCN at —90 °C provided vinylallene 71 as a 1 3 mixture of E and 2 isomers with 20% and 74% ee, respectively. This mediocre selectivity might be attributable to race-mization of the allene by the cuprate or other reactive copper species formed in the reaction mixture. The use of phosphines as additives, however, can effectively prevent such racemizations (which probably occur by one-electron transfer steps) [47]. Indeed, vinylallene 71 was obtained with an ee of 92% for the E isomer and of 93% for the 2 isomer if the substitution was performed at —80 °C in the presence of 4 eq. of nBusP. Use of this method enabled various substituted vinylallenes (which are interesting substrates for subsequent Diels-Alder reactions Sect. 4.2.2) to be prepared with >90% ee. 

Toward the biomimetic synthesis of chloropupukeananin, Kobayashi et al. [22] successfully implemented a domino sequence of two pericyclic reactions. Masked benzoquinone 59 as the diene reactant classifies the Diels-Alder reaction as inverse-electron-demanding one to which the vinylallene 58 can contribute its extra double bond forming a caged skeleton for the subsequent carbonyl-ene reaction. Longer reaction times and higher pressures were able to direct the reaction pathway toward the desired endo product 60 against the backdrop of numerous conceivable side mechanisms. Choosing the pure enantiomer of 59, as depicted in Scheme 6.12, furthermore increased the stereoselectivity and completed the synthesis of the model compound 61 in 70% yield. 

Scheme 6.32 A propargylic ene reaction forming a vinylallene as the diene part of a subsequent Diels-Alder reaction in the preparation of six-membered ring systems.

The mechanism of reaction involves a process consisting of an intramolecular ene reaction between two alkynes to give a vinylallene intermediate, which then undergoes an intramolecular Diels—Alder reaction with the double bond to give the fused tetracyclic product. 

Hetero-Diels-Alder-type cydoaddition reactions of the vinylallenes with aldehydes proceeded in the presence of BF3 OEt2 (l.lequiv.) at 0°C to give the adducts in a moderate endo exo ratio. The cydoaddition took place from the less hindered face of the vinylallene [168]. 

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