Spirocyclization reaction

A crystal structure is available for the compound with R = HC=C(CH2)2, and a mechanism was also proposed. On changing the reaction conditions (CH3CN, 82°C) and using Af-propionylimidazole, a tricyclic imidazo[l, 2 l,2]pyrrolo[2,3-6]furan was obtained in a diastereoselective spirocyclization reaction tl59],[157]... 

Palladium-catalyzed reaction of bromo dienes 39 was complete after a few hours, and afforded spirocycles 40a and 40b as single regio- and stereoisomers (Scheme 12). The Heck spirocyclization reaction is regioselective, giving five-membered heterocycles. In addition, it is stereoselective because the Heck adducts were obtained as single geometric isomers [60]. 

First, on the basis of the hypothesis by Munro and co-workers shown in Scheme 1, we examined the biosynthetically plausible route from makaluvamine F using our previously developed oxidative spirocyclization reaction with PIFA. As a result, the oxidative cyclization of makaluvamine F as well as the trimethylsily-lated makaluvamine F using PIFA under various conditions yielded a complex mixture, probably due to the high reactivity of the iodine(III) reagent toward the sulfide (Scheme 28). 

Hypervalent iodine induced oxidative dearomatization of orf/io-substituted phenolic substrates in the intramolecular mode has been realized as an enantioselective reaction. In particular, Kita and coworkers have developed the enantioselective spirocyclization reaction of the orfho-substituted phenolic substrates 275 using chiral aryliodine(III) diacetate 276 having a rigid spirobiindane backbone (Scheme 3.115) [346]. Similar enantioselective oxidative spirocyclization reactions of the ort/io-substituted phenolic substrates under catalytic conditions in the presence of chiral iodoarenes or chiral quaternary ammonium iodide catalysts are discussed in Sections 4.1.6 and 4.4. 

The oxidative dearomatization of appropriately substituted phenolic substrates resulting in intramolecular cyclization with the formation of spirocyclic products represents one of the most powerful synthetic tools in modern organic synthesis (Seetion 3.1.11). Kita and coworkers were the first to report a catalytic variant of the oxidative spirocyclization reaction based on the in situ regeneration of a [bis(trifluoroacetoxy)iodo]arene from iodoarene using mCPBA as a terminal oxidant [2]. In a representative example, the oxidation of... 

In the following example, a phenolic substrate was treated with PIFA to cause an oxidative dearomatization/spirocyclization reaction. Spirooliga-nones A and B were formed in 5-exo-trig cyclization manner exclusively (14OL3740). 

Oxidative dearomatizations with introduction of nitrogen nucleophiles are rather rare in reports. Sorensen and co-workers describe the total synthesis of a powerful immunosuppressant (FR901483) by oxidative aza-spiroannulati(Hi with PIDA in HFIP followed by an intramolecular aldol addition (Scheme 12, top) [77]. Similar to Sorensen s procedure, Hrmda and co-workers completed the formal total synthesis of enantiopure (-)-TAN1251A by dearomatizing spirocyclization reaction of the enantiopure chiral phenol substrate with high stereocontrol at the diastereomeric spiro center [78]. 

Kigoshi s formal synthesis (Scheme 1.54) relies on the efficient spirocyclization reaction of ketone 296 also prepared from 3-carene. The AC ring system was then further elaborated into 1,8-diene 298 that could be cyclized to 299 in 87% yield using [Ru]-II (25 mol%). A dramatic temperature and solvent effect was observed as no reaction took place in dichloromethane. AUylic oxidation then delivered aldehyde 300, an intermediate in Winkler s total synthesis of ingenol [74]. 

Intramolecular reactions of electron donor and acceptor sites in cyclic starting materials produce spirocyclic, fused, or bridged polycyclic compounds. 

Alkenes in (alkene)dicarbonyl(T -cyclopentadienyl)iron(l+) cations react with carbon nucleophiles to form new C —C bonds (M. Rosenblum, 1974 A.J. Pearson, 1987). Tricarbon-yi(ri -cycIohexadienyI)iron(l-h) cations, prepared from the T] -l,3-cyclohexadiene complexes by hydride abstraction with tritylium cations, react similarly to give 5-substituted 1,3-cyclo-hexadienes, and neutral tricarbonyl(n -l,3-cyciohexadiene)iron complexes can be coupled with olefins by hydrogen transfer at > 140°C. These reactions proceed regio- and stereospecifically in the successive cyanide addition and spirocyclization at an optically pure N-allyl-N-phenyl-1,3-cyclohexadiene-l-carboxamide iron complex (A.J. Pearson, 1989). 

A redox process also occurs in the reaction of selenium diimides with bis(amino)stannylenes. Eor example, the cyclic stannylene McaSi)//-N Bu)2Su reacts in a 1 1 molar ratio with BuN=Sc=N Bu to give a spirocyclic tin complex, which reacts with a second equivalent of the stannylene to generate a Sn-Sn bond [d(Sn-Sn) = 2.85 A, /( Sn- Sn) = 13,865 Hz)] (Scheme 10.6). ... 

Dehydration of a spirocyclic quaternary salt such as 147 gives rise to a 3,4-dihydro-y-carboline (148). This reaction is not, however, of general applicability since both 149 (R = C2H5) and 149 (R = CH2C6H5) yield the fully aromatic carbolinium salt 150 under the same conditions. 

A series of interesting pyrazolo[3,4-(f pyrimidine derivatives was obtained by a thermal denitrocyclization reaction of hydrazones, e.g. 164 or 166, easily formed from the corresponding aldehyde or ketone hydrazones with halo-nitrouracil derivatives, e.g. 163 (71CC1442, 72CC298). Intermediates 164 or 166 can be isolated and their cyclization in suitable solvents (methanol, DMF, DMSO) provided high yields of the products. Aldehyde hydrazones yielded the corresponding l,7-dihydropyrazolo[3,4-J]pyrimidines, e.g. 165, whereas ketone hydrazones gave l,5-dihydropyrazolo[3,4-pyrimidine derivatives, e.g. spirocyclic compound 167 (Scheme 26). 

The Simmons-Smith reaction is well suited for the synthesis of spirocyclic compounds. It has for example been applied for the construction of the fifth cyclopropane ring in the last step of a synthesis of the rotane 8 ... 

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

In the synthesis of spirocyclic systems via an intramolecular Sakurai reaction, allylsilanes with an allyl moiety attached to the 3-position of the 2-cyclohexenone are required as starting materials. 

Ordinary aldehydes and ketones can add to alkenes, under the influence of UV light, to give oxetanes. Quinones also react to give spirocyclic oxetanes. This reaction, called the Patemo-BUchi reaction,is similar to the photochemical dimerization of alkenes discussed at 15-61.In general, the mechanism consists of the addition of an excited state of the carbonyl compound to the ground state of the alkene. Both singlet (5i) and n,n triplet states have been shown to add to... 

In a related reaction, treatment of spirocyclic oxaziridines with MnCl(TPP), where TPP = m o-tetraphenylporphyrinate (2 — ), or photolysis leads to a lactam. 

Another approach to a donor adduct of the methylene phosphenium cation is the addition of a phosphonium cation to the phosphaalkyne. The reaction of the protic cation [HPPhal + lCFaSOa] with CjoHuCP produced a white powder which was identified as the P-phosphonio-substituted phosphaalkene [74]. Alternatively to the elimination reaction the phosphaalkynes were protonated. C-protonation of adamantylphosphaacetylene and ferf-butylphosphaacetylene occurred in superacid media under formation of phosphavinyl cations. From these spirocyclic betaines by reaction of l-Ad-C=P (Ad = adamantyl) withB(OTf)3 a phosphavinyl cation could be detected [75]. 

The only structurally characterized derivative of a trisimido organophos-phonate anion is the spirocyclic tellurium(IV) complex (19), which is obtained from the interesting redox reaction between PhPCl2 and [Li2Te(N Bu)3 ] 2 [27]. The phosphorus(V)-centered ligands are generated by imide transfer from tellurium to the phosphorus(III) atoms with concomitant reduction of one-half of the tellurium in the Te(IV) reagent to elemental tellurium [27]. 

Nair and co-workers have demonstrated NHC-catalysed formation of spirocyclic diketones 173 from a,P-unsaturated aldehydes 174 and snbstitnted dibenzylidine-cyclopentanones 175. Where chalcones and dibenzylidene cyclohexanones give only cyclopentene products (as a result of P-lactone formation then decarboxylation), cyclopentanones 175 give only the spirocychc diketone prodncts 173 [73]. Of particular note is the formation of an all-carbon quaternary centre and the excellent level of diastereoselectivity observed in the reaction. An asymmetric variant of this reaction has been demonstrated by Bode using chiral imidazolium salt 176, obtaining the desymmetrised product with good diastereo- and enantioselectivity, though in modest yield (Scheme 12.38) [74],... 

The reactions of the six-membered chlorocyclophosphazene were studied with a number of aliphatic diamines (169 175), aromatic diamines (176), aliphatic diols (177-179), aromatic diols (180,181) and compounds containing amino and hydroxyl functional groups (169,170,182). This subject has been reviewed (11,16,20). There are at least five different reaction products that are possible (Fig. 19). Replacement of two chlorine atoms from the same phosphorus atom produces a spirocyclic product. Replacement of two chlorine atoms from two different phosphorus atoms in the same molecule produces an ansa product. Reaction of only one end of the difunctional reagent, resulting in the substitution of only one chlorine atom, leads to an open-chain compound. Intermolecular bridged compounds are formed when the difunc-... 

With aliphatic diols, although mixtures of products are formed, the predominant products are spirocycles 11,177). The reactions with the sodium salts of etheroxy diols such as tetra- and pentaethylene glycols... 

---