Base-induced, addition

Tolylaulfonylmethyl isocyanide is a useful and versatile reagent in organic chemistry. It has been used for the synthesis of several azole ring systems by base-induced addition of its C—N=C moiety to various... 

In addition to direct DuPhos and BPE analogues, several other ligands containing five-membered phosphacycles have been reported (Fig. 24.6). As early as 1991, non-C2-symme trie phospholane-containing phosphines 37-39 were reported by Brunner and Limmer [7]. These were prepared by base-induced addition of the secondary phospholane to the appropriate diphenylphosphino-substi-tuted olefin. As for the symmetrical 3,4-disubstituted bisphospholanes, enantios-electivities for the Rh-catalyzed reduction of a-acetamidocinnamate were poor. 

Chiral 1,2,3,4-tetrahydropyridine 192 derived from (h )-l -phenylcthylarninc undergoes base-induced addition of methyl vinyl ketone to give a 2 1 separable diastereomeric mixture of m-fused octahydro-quinolin-7-ones 193 and 194 (Equation 16) <2001TA2099>. 

Several 2-substituted 3,4-diarylpyrroles 3 have been prepared in a regioselective process employing the base induced addition of methyl isocyanoacetate to the a,f -unsaturated nitriles 4, and one of the pyrroles so obtained was used in a concise synthesis of the alkaloid ningalin B... 

In their investigation of [Fe2(CO)j(//-SH)2] as an inorganic mimic of mercaptans, RSH, Seyferth and group studied the base-induced reactions of [Fe2(CO)6(//-SH)2] (516) with activated olefins and acetylenes. Like mercaptans, 516 undergoes base-induced addition to a,/ -unsaturated sys-... 

The first sodium amalgam-induced dimerization of acrylonitrile to adiponitrile [29] was performed in aqueous solution, and the yield was discouragingly low (5%). Mainly, a base-induced addition of water resulting in p, -bis(cyanoethyl) ether occurred together with a reduction to propionitrile (PN). 

The 1,4-oxaphosphinane system was not known until 1974, when Samaan reported the synthesis of the quaternary 1,4-oxaphosphinanes (e.g. (320)), 1,4-thiaphosphinanes and 1,4-azaphosphinanes by base-induced addition of H2O, H2S and MeNH2 to the diallyldiphenylphosphonium salts (319) (Equation (24)) <74TL3927, 78CB579). 

In an extension of previous work, it has been found that Pd(0)-catalysed intramolecular cyclization of allylic acetates (21) can be used to prepare the chrysanthemic acid analogues (22). The potentially useful cw-cyclopropane (23) can be simply obtained by base-induced addition of cyanoacetate to ethyl 2-bromo-3,3-dimethylacrylate followed by decarboxylation oddly, a similar reaction using malonate fails to give a cyclopropane. Optically pure dichloro cw-chrysanthemic acid (26) has been obtained by a Favorskii rearrangement of the chiral cyclobutanone (25) prepared from the keten (24) by sequential [2 + 2]cycloaddition, cine-rearrangement, and resolution (Scheme 3). ... 

An approach to an anthracycline, 8,10-dideoxycarminomycinone (204), which does not involve a Diels-Alder reaction, is by base-induced addition of the nitro-acetal (202) to the anthraquinone (201) resulting in the regioselective formation of (203), which is then converted to (204) using relatively standard methodology. Also of considerable interest in this area are several different total syntheses of aklavinone (205). 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

Williams and McClymont have observed that acylation reactions of the dianion of 2-(5-oxazolyl)-l,3-dithiane (15) lead to formation of 4,5-disubstituted oxazole products through a Comforth rearrangement pathway under base-induced, low-temperature conditions. For example, deprotonation of 15 with LiHMDS (3.0 equivalents) at -78°C, followed by addition of benzoyl chloride or p-chlorobenzoyl chloride and warming to 0°C, provided 16 in 74% and 47% yield, respectively. 

The reaction of 3-methoxy-1,2,4-triazine 1-oxide 20 with the carbanion generated from chloromethyl phenyl sulfone proceeds as the vicarious nucleophilic substitution (VNS) of hydrogen (Scheme 1, path B) via addition of the carbanion at position 5 of the heterocycle. Following base-induced elimination of HCl and protonation, 3-methoxy-5-phenylsulfonyl-1,2,4-triazine 4-oxides 65 result (88LA627). 

Introduction of an additional methyl group on the donor atom of TMM moiety gives a low 33% yield of the perhydroindans (49, X=H2) and (50, X=H2) with substantial production of the diene by-products [24]. However, it is still remarkable that the reaction works at all since the corresponding intermolecular cycloaddition failed. Incorporation of a carbonyl moiety adjacent to the donor carbon atom doubles the yield of the cycloadducts to 66% (Scheme 2.15). This so-called acyl effect works by making the donor carbon of the TMM unit "softer," thus facilitating the initial step of the conjugate addition, as well as inhibiting base-induced side reactions [22]. 

A sequence of straightforward functional group interconversions leads from 17 back to compound 20 via 18 and 19. In the synthetic direction, a base-induced intramolecular Michael addition reaction could create a new six-membered ring and two stereogenic centers. The transformation of intermediate 20 to 19 would likely be stereoselective substrate structural features inherent in 20 should control the stereochemical course of the intramolecular Michael addition reaction. Retrosynthetic disassembly of 20 by cleavage of the indicated bond provides precursors 21 and 22. In the forward sense, acylation of the nitrogen atom in 22 with the acid chloride 21 could afford amide 20. 

It is appropriate at this juncture to address some of the more useful transformations of 2,3-epoxy alcohols.913 A 2,3-epoxy alcohol such as compound 14 possesses two obvious electrophilic sites one at C-2, and the other at C-3. But in addition, C-l of a 2,3-epoxy alcohol also has latent electrophilic reactivity. For example, exposure of 14 to aqueous sodium hydroxide solution results in the formation of triol 19 in 79% yield (see Scheme 5). In this interesting transformation, hydroxide ion induces the establishment of an equilibrium between 2,3-epoxy-l-ol 14 and the isomeric 1,2-epoxy-3-ol 18. This reversible, base-induced epoxide migration reaction is a process known as the Payne rearrangement.14... 

The intramolecular Michael addition11 of a nucleophilic oxygen to an a,/ -unsaturated ester constitutes an attractive alternative strategy for the synthesis of the pyran nucleus, a strategy that could conceivably be applied to the brevetoxin problem (see Scheme 2). For example, treatment of hydroxy a,/ -unsaturated ester 9 with sodium hydride furnishes an alkoxide ion that induces ring formation by attacking the electrophilic //-carbon of the unsaturated ester moiety. This base-induced intramolecular Michael addition reaction is a reversible process, and it ultimately affords the thermodynamically most stable product 10 (92% yield). 

The activation of silylene complexes is induced both photochemically or by addition of a base, e.g. pyridine. A similar base-induced cleavage is known from the chemistry of carbene complexes however, in this case the carbenes so formed dimerize to give alkenes. Finally, a silylene cleavage can also be achieved thermally. Melting of the compounds 4-7 in high vacuum yields the dimeric complexes 48-51 with loss of HMPA. The dimers, on the other hand, can be transformed into polysilanes and iron carbonyl clusters above 120 °C. In all cases, the resulting polymers have been identified by spectroscopic methods. 

Mono- and l,3-di-ter/-butylcyclopentadienyllithium Li(Bu Cp) 4 (n = 1) and 5 (,n = 2) can be obtained directly by addition of methyllithium to 6,6-dimethyl fulvene and 2-/ert-butyl-6,6-dimethyl fulvene, respectively [27a]. Since the fulvenes themselves are easily accessible by base-induced condesation reactions [27b], this method offers a viable alternative to the usual metalation of the substituted cyclopentadienes 1 and 2 (Eq. 2). 

Base-induced eliminative ring fission, in which both the double bond and the sulfone function take part, has been observed in thiete dioxides253. The reaction can be rationalized in terms of initial Michael-type addition to the double bond of the ring vinyl sulfone, followed by a reverse aldol condensation with ring opening. The isolation of the ether 270c in the treatment of 6c with potassium ethoxide (since the transformation 267 -> 268 is not possible in this case) is in agreement with the reaction mechanism outlined in equation 101253. 

The stereoselectivity of these reactions arises from a base-induced anti elimination after the migration. The elimination is induced by addition of methoxide to the boron, generating an anionic center. 

Other examples of the ElcB pathway are benzyne formation from C6HsF (cf. p. 174), reversal of simple nucleophilic addition to 0=0, e.g. base-induced elimination of HCN from cyanohydrins (20 cf. p. 212),... 

The regioselective addition of nitryl iodide to alkenes, followed by base-induced elimination, gives nitroalkenes. Nitryl iodide is generally prepared by the reaction of AgN02 and iodine. 

Benzannulated NHPs are straightforwardly accessible from AUV-disubsti luted o-phenylenediamines either via base-induced condensation with substituted dichlorophosphines [25] or PC13 [26], or via transamination with tris(dialkylamino) phosphines [13, 14, 27], respectively. An analogous NH-substituted derivative was obtained in low yield via transamination of o-phcnylcncdiaminc with ethoxy-bis(diethylamino)phosphine [28], and condensation of o-phenylenediamine with excess tris(diethylamino)phosphine furnished a l,3-bis(phosphino)-substituted heterocycle [29], Intermediates with one or two NH functions were detectable by spectroscopy but could not be isolated in pure form under these conditions. However, 2-chloro-benzo-l,3,2-diazaphospholene and the corresponding 1-phenyl derivative were prepared in acceptable yield via condensation of PC13 with o-phenylenediamine under microwave irradiation [30], or with A-phenyl-o-phenylenediamine under reflux [27], respectively, in the absence of additional base. The formation of tetrameric benzo-NHPs during transamination of A-alkyl-o-phenylenediamines with P(NMe2)3 has already been mentioned (cf. the section entitled 1,3,2-Diazaphospholes and 1,3,2-Diazaphospholides ). 

---