Vinylsilane-mediated spiroannulation. Synthesis of spiro[4.5]decadienones

Abstract

mechanisms: (a) intermediate 3 or (b) another intermediate formed from 3 by loss of the leaving group is trapped by reaction with sulfite ion or thiamin. Consequently, simpler mechanism a is given in Scheme I. Incorporation of an additional step as required by pathway b does not change the kinetic form, only the collection of rate cons tan ts .The derivation pertains to experimental conditions3 where sulfite ion S is the limiting reagent under initial rate conditions and 1 is present in excess. The pH dependence is not expressed but it is to be understood that the conjugate acid of thiamin reacts with free sulfite ion while thiamin base is a nucleophile.Step k3 is not included in the rate expression because one S is consumed and another is liberated. Note that S is liberated in step k4 in which thiamin traps intermediate; the formation of oligomer is catalyzed by S, and so step k4 must be included in the rate expression. Applying a steady-state assumption for 3 gives eq 2. This has the form of eq 1 in ref 3, kz + k 4 [ l ] being an apparent constant. The k2/k3 ratio in ref 3 now becomes (k, + k 4 [ l ] ) / k 3 and reduces to k 4 [ l ] / k 3 if k2 < k 4 [ l ] .We actually prefer a scheme in which the two nucleophiles compete for an intermediate which already has lost the leaving group and therefore use different symbols k B / k s in eq 1 to express the competition. In this case no assumption needs to be made about the relative magnitudes of kz and k , [ l ] .Highly instructive is a consideration of the case wherei.e., intermediate is trapped preferentially by 1. As eq 3 shows, the rate of disappearance of sulfite ion now is second order in sulfite ion.(3)By use of our value for k B / k s and the concentrations given in ref 3 calculations show that sulfonate ion 2 is the major product at high pH. But as the acidity is lowered and the ratio of thiamin base to sulfite ion concentrations increases the major product becomes bispyrimidine 4 as the reaction becomes second order in sulfite ion.1° Registry No. l.HCl,67-03-8; 5,77028-14-9; sulfite ion, 14265-45-3. S c h e m e I6 ' Me,Si 2 aq HCI quench * 2a, R = H; R = Me b, R = Me; R' = i-Bu 3a, R = H (93%) 4a, R = H (96%) b, R = Me (77%) b, R = Me (99%) '8 1 2 Jones o x o l y l o x d n chloride, Phd-'6 3 TiCIq,CH2C12, -3 0 -2 5 "C I I 5a, R = H (90%) b , R = M e ( 9 4 % ) la, R = H (82%) b, R = Me (84%) frameworks.2 In connection with ongoing synthetic efforts in these laboratories, we required an efficient entry to spiro[4.5]decadienones of general structure 1. The known and readily accessible dimedone derivatives 2 were seen as particularly attractive starting material^.^ We report herein a vinylsilane-mediated spiroannulation sequence which effects the desired overall transformation of the vinylogous esters 2 to the spirodienones 1 in excellent yield.4 R go* R ' O RyJ I I 2a. R = H: R' = Me l a , R = H b; R = Me; R = i-Bu b, R = Me Treatment of dimedone methyl ether (%a) with trans-P-(trimethylsilyl)vinyllithium5 (-78425 "C) followed by a quench with 5% aqueous HC1 pr...

Stereochemical Control in Organic Synthesis Using Silicon-Containing Compounds

“…The stereochemistry is not, therefore, necessarily determined by the double-bond geometry, but it affects it. The usual observation, whenever both stereoisomers have been tried, − is that the cis -vinylsilanes 131 react faster and more cleanly than the trans - 132 , but cyclization, with the inevitable inversion of configuration, has been seen many times with trans -vinylsilanes. , Sometimes, however, the trans -vinylsilane gives an anomalous product while the cis isomer is normal, and the wrong geometry in the double bond, even when it is exocyclic, can lead to other anomalies 30 …”

Ring forming reactions: adjustable regiocontrol on a polyfunctional substrate

“…authentic metopon, mp 238-244 °C dec) 240-246 °C dec. Both its IR and NMR spectra were indistinguishable from those of authentic metopon: IR (Nujol) 3530, 3400 (br), 1730,1610,1250, 1030, 850, 800 cm'1 2inter alia; NMR 1.59 (s, 3 H), 2.45 (s, 3 H), 6.59 and 6.70 (AB, 2 H) inter alia.…”

“…When a solution of the cyclopentenone 1 in tetrahydrofuran (THE) at -35 °C was treated with 1 equiv of TiCl4 followed by 2 equiv of iV-methylanilinium trifluoroacetate (TAMA)4 56and allowed to warm slowly to ambient temperature, there was obtained a 50% yield of crystalline 7-formyl-6,8,8-trimethylspiro[4.4]nona-1,6dien-3-one (4, mp 108-111 °C) as the sole isolable product. 5,6 It was noted with little satisfaction that in 4 (C13H1602) we had managed to generate an isomer of the targeted tricyclic 2.…”

“…Finally, a third reaction pathway (which for our ultimate purpose was the desired result) was brought cleanly into effect to provide the crystalline Michael addition product 6 (mp 68-70 °C) in high yield. The functionalized cis-fused bicyclo[3.3.0]octane derivative 6 was produced in 92% yield5 by refluxing a solution of 1, 2 equiv of morpholine, and a catalytic amount of p-TsOH in benzene under a Dean-Stark trap.6…”

Silicon-Mediated Organic Synthesis

“…1 Still more impressive are the recent advances in organic synthesis which have as their basis intramolecular variants of this concept. The vinylsilane-mediated spiroannulation sequence which effects facile overall conversion of 21 to spirodienone 22 (28) and the iminium ion-vinylsilane cyclization 23 to 24 which stereospecifically assembies the (Z)-6-alkylideneindolizidine ring system known as dendrobatid toxin 25 ID are particularly noteworthy (29). Where silylacetylenes are concerned, free radical conditions can be applied to achieve addition across the triple bond.…”