Ynals

An example of the Diels Alder reaction of furans is the cycloaddition of 31 with 4,4-diethoxybut-2-ynal (32) which acts as an acetylenedicarbaldehyde synthon to afford 7-oxabicyclo [2.2.1]heptene derivatives [29] which were then converted into substituted cyclohex-l-ene-l,6-dicarbaldehydes by a four-step procedure (Scheme 2.14). 

H-Pyran-2-iminium salts (2) are formed by the acid-catalysed cyclisation of the pentadienal (1), itself accessible from the addition of HCl to 5-dimethylaminopenta-2-en-4-ynal, a push-pull enyne <96HCA192>. 

Macrolactones 77 and/or 78 can be prepared from the reductive cyclisation of ynals 76 in the presence of NHC-nickel complexes (Scheme 5.21) [21], This maaolactonisation occnrs with different selectivity depending on the ligands attached to the nickel. If carbenes snch as IMes or IPr are nsed, the exocyclic olefin 77 is preferentially obtained, however when phosphine ligands are nsed, the endocyclic adducts 78 are preferentially obtained. 

Scheme 5.21 Macrolactones prepared from the reductive cyclisation of ynals in the presence of NHC-nickel complexes...

Related redox transformations allow the conversion of ynals to a,P-nnsaturated esters [33], as well as the ring expansion of formyl P-lactams [34], oxacycloalkane-2-carboxaldehydes [35], and 2-acyl-1-formyIcyclopropanes [36], Farther developments allow the synthesis of amides from a range of a-fnnctionalised compounds, but require an additive (imidazole, HO At or HOBt) for efficient amidation [37],... 

In addition to the methodological advances noted above, the Et3SiH variant was utilized in the total synthesis of three members of the allopumil-iotoxin family [ 15,16]. In one of the more complex examples, ynal substrate 1 was converted to product 2 in 93% isolated yield as a single diastereomer (Scheme 4). Simple removal of the protecting groups allowed completion of... 

Even fully substituted aromatic compounds can be prepared utilizing the Mi-chael/Dieckmann strategy. As reported by Covarrubias-Zuniga and coworkers (Scheme 2.32) [67], reaction of the anion of l-allyl-l,3-acetonedicarboxylate (2-138) and the ynal 2-139 afforded the intermediate 2-140 which led to the resorcinol 2-142 with spontaneous aromatization under acidic conditions via 2-141 in an overall yield of 32 %. 2-142 was transformed into mycophenolic acid (2-143) in only a few additional steps [68]. 

G s-3-methyl-2-penten-4-ynal 72 was converted to the ketone 176 which on coupling under Glaser conditions led directly to the annulenediones 177 and 17861 ... 

Unexpected transformations of 5-(phenylthio)pent-2-en-4-ynal and 5-(methylthio)pent-2-en-4-ynaI to 2-bis(phenylthio)- and 2-bis(methylthio)methylfurans respectively in the presence of a slight excess of HCl have been recorded. The transformations are expected to involve a pyran to furan ring-contraction sequence <00HCA1191>. 

Elimination routes are also popular in this area of allene hydrocarbon chemistry. For example, hydrosilylation of ynals 159 with triethylsilane in the presence of a rhodium catalyst leads to the a-triethylsilylenals 160 (Scheme 5.23) [64]. 

Fig. 4.2 Possible mechanisms for the formation of (a) cyclopentanones from 4-all

Ojima has reported the catalytic cyclization/hydrosilylation of ynals to form silylated alkylidene cyclopentanols." For... 

Intramolecular 2 + 2 + 2-cycloisomerizations of cyclic triynes and enediynes have been reported with RhCl(CO)(PPh3)2.126 The transition metal-catalysed rearrangement of alk-5-ynals to /-alkynyl ketones and cyclopent-l-enyl ketones was developed using [Rh(P(OPh)3)2]BF4 or Cu(OTf)2 as a catalyst and the effect of substituents on the partition to products was elaborated (Scheme 84).127... 

The same group of workers has developed a method for the closure of the 3,4-bis(but-2-ynal)azetidinone 283 using Pedersen vanadium(n)-mediated pinacol coupling to give the vie-diol 284 from which it was possible to get the bicyclic enediyne in two steps and 63% overall yield from the diol <2000EJ0939> (see Section 2.04.7.2). 

This procedure was later used for the macrocyclization of ynals (Scheme 5) [43]. Macrocyclic rings ranging in size (e.g., 14- to 22-membered rings) and all possessing endocyclic E-olefins were obtained from terminal ynals in good yields (62-70%) using a catalyst derived from Ni(COD)2, KO(Bu, and IMes - HC1. Internal alkynes were also examined. Phenyl-substituted alkynes... 

Ynals can be selectively hydrosilylated in the presence of Pt salts leading to a-triethylsilyl enals, which undergo 1,2-addition of Grignard reagents followed by Peterson elimination from the intermediate alcohol. This method offers a simple synthetic route from ynals to the corresponding allenes.267... 

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