Stemodine

The silyl enol ethers 209 and 212 are considered to be sources of carbanions. and their transmetallation with Pd(OAc)2 forms the Pd enolate 210. or o.w-tt-allylpalladium, which undergoes the intramolecular alkene insertion and. 1-elimination to give 3-methylcyclopentenone (211) and a bicyclic system 213[199], Five- and six-membered rings can be prepared by this reaction[200]. Use of benzoquinone makes the reaction catalytic. The reaction has been used for syntheses of skeletons of natural products, such as the phyllocladine intermediate 214[201], capnellene[202], the stemodin intermediate 215[203] and hir-sutene [204]. 

The syntheses of stemodin and stemodinone, structural relatives of aphidicolin, were accomplished using the A/B double annulation and B/C spiro annulation processes developed for the assembly of aphidicolin. 

Otsuka K-76, a fungal product with strong anticomplement activity, was synthesized from the A/B bicyclic precursor of stemodin. The aromatic subunit was retrosynthetically disconnected to a symmetrical precursor. A surprising non-selectivity of olefinic hydroxylation by osmium tetroxide was noted. 

Stereoselective reaction with ketones. The reaction of ketone 1 with methyl-lithium, trimethylaluminum, and lithium letramethylaluminate shows no stcrco-specificity. The reaction with mcthylmagncsium bromide gives the two possible adducts in the ratio 2.4 1. The best stereospccificity is observed with dimethylsulf-oxonium methylide, which converts 1 into 2 and 3 in a ratio about 5 1. Reduction of the epoxides with lithium triethylborohydride gives the desired tertiary alcohols. This reaction was used in a synthesis of ( ) stemodin (4).2... 

Transmetallation of silyl enol ethers of ketones and aldehydes with Pd(II) generates Pd(II) enolates, which are usefull intermediates. Pd(II) enolates undergo alkene insertion and -elimination. The silyl enol ether of 5-hexen-2-one (241) was converted to the Pd enolate 242 by transmetallation with Pd(OAc)2, and 3-methyl-2-cyclopentenone (243) was obtained by intramolecular insertion of the double bond and -elimination [148], Formally this reaction can be regarded as carbopalladation of alkene with carbanion. Preparation of the stemodin intermediate 246 by the reaction of the silyl enol ether 245, obtained from 244, is one of the many applications [149]. Transmetallation and alkene insertion of the silyl enol ether 249, obtained from cyclopentadiene monoxide (247) via 248, afforded 250, which was converted to the prostaglandin intermediate 251 by further alkene insertion. In this case syn elimination from 250 is not possible [150]. However, there is a report that the reaction proceeds by oxypalladation of alkene, rather than transmetallation of silyl enol ether with Pd(OAc)2 [151]. 

Sodium trithiocarbonate, 369-370 Spiroannelation, 240, 266-267, 443 Spiro [4.5 ] decadienones, 443 Spiro [4.5 ] decenes, 266-267 Spiro-[4.5]decenones, 100 Spirolactones, 8, 155,192 Stabase adducts, 140 Stannic chloride, 370-373 Stannous chloride-Silver perchlorate, 374 Stannous fluoride, 374 Stannoxanes, 124 Stemodin, 169... 

The biological activity of the diterpenoids of the aphidicolin-stemodin series makes these compounds attractive targets. The total synthesis of stemodin (96) has been described.172 The key spiro-centre at C-9 was constructed by the internal aldol condensation of the keto-aldehyde (97) to afford (98). Several stereoselective syntheses of aphidicolin have been reported with different solutions to the problem... 

Cycloaddition (cf. 12,163). In the presence of CpCo(CO)2, the monocyclic enync (Z)-l cyclizcs to the tetracyclic diene (2) as a 2 1 mixture of epimers. The product has the carbon skeleton present in the ditcrpenc stemodin (3), and can be converted in three steps to an intermediate in a total synthesis of the diterpene. This cycloaddition fails with (E)-l. 

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