Spirocyclic intermediate

In this synthesis, a tandem vicinal difunctionalization of enone 18 provides an exceedingly simple solution to the task of synthesizing spirocyclic intermediate 16. When 18 is treated with the or-ganocuprate reagent, t-Bu2Cu(CN)Li2, a smooth 1,4- or Michael ad-... 

Concealed within spirocyclic intermediate 16 are rings B and F of ginkgolide B. Intermediate 16 is readily formed in two steps from a readily available starting material and it contains a strategically placed ketone carbonyl group which provides several options for further advance. A particularly straightforward route to 15 includes the conversion of ketone 16 into enol triflate 21 by means of McMurry s protocol.16 Thus, enolization of 16 with LDA in dimethoxyethane at -78 °C followed by triflation of the enolate oxygen atom with /V-phenyltrifluoromethanesulfonimide furnishes enol triflate 21 in a yield of 80%. 

In the synthesis of l,3-dithiolan-2-ones from spirocyclic intermediates, via episulfides, substituted tetrathiacyclododecane and the related pentathiacyclopentadecane were isolated in good yields <96JCS(P1)289>. Preparation and molecular dynamics studies of 2,5,8,17,20,23-hexathia[9.9]-p-cyclophane have been reported <96P4203>. The syntheses and properties of thiocrowned l,3-dithiole-2-thiones and their conversion to tetrathiafiilvenes via treatment with triethylphosphine have been described <96LA551>. 

MgS04, the tetracycles 2-648 were obtained with excellent diastereoselectivity in reasonable yield. The reaction presumably starts with a condensation of the aldehydes 2-645 with the benzyl-protected amine moiety of 2-644 to give an iminium ion which can subsequently cyclize to afford the spirocyclic intermediates 2-646. A [3,3] sigmatropic Cope rearrangement then forms the nine-membered cyclic enamines 2-647 which, after protonation, act as the starting point for another indole iminium cyclization to provide the tetracycles 2-648 via 2-647. 

Two additional synthetic routes to ( )-j8-vetivone (350) have been developed. In one of these a suitably substituted spirocyclic system [cf. (349)] is constructed by addition of Me2CuLi to the fulvene derivative (348)/ Subsequent functional group modification (cf. Scheme 32) provides ( )-j8 -vetivone (350). In the other total synthesis d the well-known intramolecular alkylation of para-substituted phenols has been used to produce a spirocyclic intermediate (353) which can be converted into ( )-/3-vetivone (350) (cf. Scheme 33). 

It should be noted that according to the distribution of the polar functionalities opposite results should have been obtained. However, a faster tautomerization than fragmentation in the nisyl system and a difference in mechanistic details for the two series might be responsible for the unexpected observations. Perhaps a spirocyclic intermediate is involved in the fragmentation of the nisyl derivative. 

The kinetically stabilized silylene 132 easily reacted with carbon disulfide to afford the four-membered Si-S-Si-C framework. The formation of product 133 most probably proceeded via double addition of silylene 132 to the C=S double bond followed by rearrangement of the spirocyclic intermediate (Scheme 48) <1996PAC895>. 

Other symmetrical intermediates originaliy identified by radioactive labelling include the cyciopropanone in the Favorskii rearrangement in Chapter 37, p. 990, and a spirocyclic intermediate in electrophilic substitution on an Indole in Chaptar 43, p. 1170. 

A muscone synthesis involves selective intramolecular acylation at a vacant thiophene -position (Scheme 39). When intramolecular acylation reactions onto a -position of a thiophene or a pyrrole are attempted, a spirocyclic intermediate is formed in some cases with the result that rearranged products are formed (Scheme 40). 

Methy11hiocinium salt 6 (preparation in Section 14.03.9.2) is transformed by base influence into an ylide intermediate 7, which undergoes a [2,3]-sigmatropic shift forming the spirocyclic intermediate 8, which is attacked by methoxide ion affording stable 9 <2002J(P1)2704> as shown in Scheme 1. 

Historically, the possibihty of obtaining intramolecular rearrangement came from the tautomeric irreversible rearrangements observed by Chapman (Scheme 2) [4,5]. In his early work. Chapman was able to demonstrate that the reaction undertakes an intramolecular pathway, i.e. via a spirocyclic intermediate. Not much later Smiles foimd another reaction causing the 1,3 shift of the substituent in the aromatic ring, involving a similar intermediate [6,7]. 

Besides electronic effects, steric effects have also been investigated. Contrary to expectations, the presence of reasonably hindered substituents at the ortho position, favours the reaction, preorganising the formation of the spirocyclic intermediate. In the presence of a single ortho substitution, the rate of reaction follows the trend t-butyl > z-propyl > methyl [21]. The... 

However, 4-phenylfuroxan (2-oxido-4-phenyl-l,2,5-oxadiazole) derivatives behave in a different way. Sulfide 197 (Scheme 59) as well as sulfone 198 decompose with evolution of NO in alkaline conditions. It was suggested that the N - O bond is cleaved in the spirocyclic intermediate 199 to give the fragile nitroso derivative 200. 

In the synthesis of the Nevirapine ring system [161], q clization of chloro-amine 392 (Scheme 127) afforded diazepinone derivatives 395 and 397 along with chloro-amide 396. Products 396 and 397 were formed via spirocyclic intermediate 393. The relative amounts of 395, 396 and 397 could be subjected... 

Okada, K., Tanaka, M. Reinvestigation of base-induced skeletal conversion via a spirocyclic intermediate of dibenzodithiocinium derivatives and a computational study using the HF/6-31G basis set. J. Chem. Soc., Perkin Trans. 1 2002, 2704-2711. 

Okada, K., Tanaka, M. Reinvestigation of base-induced skeletal conversion via a spirocyclic intermediate of dibenzodithiocinium derivatives and a computational study using the HF/6-31G basis set. Journal of the Chemical Society, Perkin Transactions 1 2002, 2704-2711. Chantrapromma, K., Ollis, W. D., Sutherland, I. O. Base catalyzed rearrangements involving ylide intermediates. Part 16. The preparation and thermal rearrangement of allylammonioamidates. J. Chem. Soc., Perkin Trans. 1 1983, 1029-1039. 

Leeper FJ (1994) Evidence for a spirocyclic intermediate in the formation of uro gen III by cosynthetase. In The biosynthesis of the tetrapyrrole pigments. Ciba Foundation Symposium, vol 180. WUey, Chichester, pill... 

Another standard method for the synthesis of 2-oxazolidinones is by reaction of epoxides with isocyanates. Although 4,5-disubstituted derivatives are not readily accessible by this route, it has been shown that iminodioxolanes (192) add to epoxides in the presence of AICI3 to afford these oxazolidinones in high yield <9lJOC2684>. The reaction proceeds through a spirocyclic intermediate (193) (Scheme 96). The reaction of vinyl epoxides with aryl isocyanates is facilitated by palladium catalysis (Equation (28)) <89TL3893>. The products are obtained by a double inversion process, but... 

The thiazolium-mediated three-component reaction of thiazolium salts 201, aryl aldehydes and dimethyl acetylenedicarboxylate provides a facile synthesis of 2-amino-2-arylfurans 202 <05OL1343>. The reaction pathway may involve the sequential nucleophilic addition of thiazol-2-ylidene 203 with the aldehyde and DMAD to form the spirocyclic intermediate 204 through the simultaneous formation of two C-C bonds and a C-O bond Selective ring opening of the spirocyclic intermediate 204 followed by hydrolysis leads to 3-aminofuran 202 via 205. 

Intramolecnlar alkenylation at a furan a- or P-position by an alkyne occurs, with the formation of bicycUc derivatives, when promoted by mercury(II) acetate (or Hg(OAc)(OTf), generated in situ from mercuric acetate and scandinm triflate). In the case of closure onto a p-position, a spirocyclic intermediate from preferred attack at the a-position, may be involved, as shown. 

In another elegant experiment, the intervention of a 3,3-disubstitnted 3H-indolium-intermediate in an overall a-snbstitution was proved by cyclisation of the mesylate of an optically active alcohol to give an optically inactive prodnct, via an achiral, spirocyclic intermediate, from initial attack at the p-position. ... 

Reduction. The reduction of a-(benzoxazol-2-ylthio) ketones with NaBH gives thiiranes via spirocyclic intermediates/... 

Several benzo-fused tetrahydropyrans have been prepared either from aryl-propanhydroperoxides in the presence of iron(II) and copper(II) salts, from the corresponding arylpropanol either by oxidation with FeS20g, or in a photochemical reaction with iodine and mercury(II) oxide (type III radical precursors). These reactions are considered to proceed via alkoxyl radical intermediates which add to the aromatic part of the molecule. Subsequent C- or O-migration in spirocyclized intermediates affords substituted chromanes. However, ionic cyclizations may significantly interfere with the key step of the C-O bond formation [57-59]. 

Motherwell s group developed an original approach to the synthesis of biaryls based on the intramolecular free-radical zjo o-substitution reaction. This includes the reaction of ortho-io o (or bromo) phenols, A -methylanilines or 7V-methylbenzamides with various arylsulfonyl chlorides to give the respective sulfonates XXX, Ai-methyl sulfonamides XXXI, or Y-acylsulfonamides XXXII. The latter are reacted with tri- -butyltin hydride in the presence of azobisisobutyronitrile (AIBN) in refluxing benzene to produce spirocyclic intermediate XXXIII, which, upon extrusion of sulfur dioxide, afforded the ort/jo-hydroxy- XXXIV, methyamino- XXXV, or iV-methyl carboxamido-substituted biphenyls XXXVI in moderate to good yields [1-4], Scheme 1. 

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