Jatrophone synthesis

Scheme 35. The Stille reaction in Wiemer and Han s synthesis of (+)-jatrophone (135).

Carbonylative coupling of vinyl triflates with organotins (12, 470-471).3 The final step in a synthesis of the macrocyclic diterpene jatrophone (2) was effected by carbonylative coupling of a vinyl triflate with vinyltin catalyzed by bis(acetonitrile)-dichloropalladium. 

Various examples of use of alkenyltin/vinyl iodide couplings in natural-product synthesis have been provided Evans and Black [33] have obtained the macrolide insecticide (+)-A83 453A [(+)-lepicidin A] (Scheme 4-7), Burke et al. the ionophore antibiotic X-14547A [34] (Scheme 4-8), Kende et al. [35] lankacidin C (Scheme 4-9), while Han and Wiemer [36] have used the combination alkenyltin/vinyl triflate in the total synthesis of (+)-jatrophone. 

In the laboratory of L.S. Hegedus, the total synthesis of (+)-ep/-jatrophone was accomplished using a palladium-catalyzed carbonylative coupling as the key step. In the endgame of the synthesis, a 3-hydroxy ketone moiety was oxidized in excellent yield to the corresponding 1,3-dione using the mild Corey-Kim protocol. 

Gyorkos, A. C., Stille, J. K., Hegedus, L. S. The total synthesis of ( )-epi-jatrophone and ( )-jatrophone using palladium-catalyzed carbonylative coupling of vinyl triflates with vinyl stannanes as the macrocycle-forming step. J. Am. Chem. Soc. 1990,112, 8465-8472. 

Lewis acid catalyzed intramolecular alkylations of silyl enol ethers containing 5n1-reactive functionality provide useful routes to a variety of carbocyclic systems. - Smith et al have employed an intramolecular Mukaiyama reaction of the enol derivative (76) to produce the tetracyclic system (77) (equation 7). This transformation was a key step in their elegant synthesis of jatrophone. The synthesis... 

Equation 12.59 shows an intramolecular cross-coupling combined with a carbonylation, which was used in the synthesis of ( )-ep/-jatrophone (47), a diter-pene that possesses antitumor activity.126 Early in investigations on the reactivity... 

An example of the successful application of the Corey-Kim oxidation of a 3-hydroxyketone to yield a 1,3-diketone in natural product synthesis is illustrated by the total synthesis of ( )-jatrophone. 12 As shown below, the presence of the C-2 methyl group of 44 allowed for the clean conversion to desired diketone 45 in one step (i.e., no need for reductive desulferization). The Corey-Kim oxidation was then actually used a second time in the sequence to introduce another ketone and ultimately afforded the desired macrolide diterpene 46. 

Similarly, the vinyUithiums 130 and 136, and the Hthiated cyclohexenic reagent 138 serve as useful building blocks for the synthesis of the macrocycHc diterpene antileukemic (it)-jatrophone (135) (1990JA8465), the sesquiterpenoid (+)-asteriscanolide (137) (2000JA2742), and the marine natural product nakienone B (139), respectively (Figure 5) (1996TL4679). 

In a paper discussing strategies for the synthesis of the macrocyclic diterpene jatrophone, brief comment is made disclosing that chromous sulphate can cleanly effect the stereospecific reduction of a-oxoacetylenes to the corresponding E-enone, analogous to the reduction of acetylenic alcohols." ... 

A full account of the synthesis of analogues of jatrophone has appeared. ... 

The Stille-Hegedus synthesis of the diterpene jatrophone took advantage of an intramolecular carbonylative Stille coupling between a vinyl triflate and a vinylstannane motif to forge the macrocycle found in the natural product (see below). 

Gyorkos et al. reported a beautiful synthetic route to accomplish the total synthesis of 2-cp/-Jatrophone (Scheme 7.12). To construct the 11-membered ring of 2-ep/-Jatrophone [25], they also turned their attention to StiUe coupling. Treatment of vinyl triflate 46 with a catalytic amount of PdCl lMeCbOj and LiCl in DMF under a carbon monoxide atmosphere (50psi) led to the desired product 49. The mechanism of this impressive reaction involved the oxidative addition of a Pd(0) species 47... 

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