Spiro-mode

When a-tethered nitroalkenes bearing three or four methylene chains and ester-activated dipolarophiles react with vinyl ethers, spiro mode tandem cycloaddition takes place to give tricyclic spiro nitroso acetals in good yield and high diastereoselectivity (Scheme 8.46).184... 

The placement of the tether at the C(3) position of the nitronate provides access to the spiro mode of dipolar cycloadditions. This class has been evaluated for the preparation of five- and six-membered spiro ring systems (Table 2.54) (254). The dipolar cycloaddition proceeds in good yields with mild heating, however, the three-atom tether proceeds faster than the four-atom tether. 

The intramolecular cycloadditions of cyclic nitronates have received much more attention. The cyclic nitronate structure provides three basic modes of intramolecular cycloaddition (Fig. 2.15). Attachment of the tether to the C(3) position of the nitronate results in the formation of a spiro system (spiro mode). However, if the tether is appended to the C(4) position of the nitronate, the dipolar cycloaddition yields a fused ring system (fused mode). Finally, if the tether is attached at any other point of the cyclic nitronate, the cycloadducts obtained will consist of bicyclic structures (bridged mode). 

Spiro-Mode and Linear-Fused-Mode Cascade Cyclization Processes via Carbopalladation... 

Both spiro-mode and linear-fused-mode cascade cyclization processes via carbopalladation were introduced in 1988 [20,21,131]. In addition to the... 

Mehta has examined relative stereocontrol in an approach to the carbocyclic nucleus of ophiobolins. Cyclization of the triquinane (11) gave two products, (12) and (13), in a 4 1 ratio (Scheme 14). These products arise from opposite rotatory pathways as shown. Surprisingly, the major product arises from conrotation to the concave face of the diquinane unit. Finally, Nazarov has provided an interesting example of both fused and spiro mode annulations in equation (10). ... 

Tandem pericyclic reactions are a powerful strategy for construction of complex, polycyclic compounds. In recent years tandem [4 + 2]/[3 + 2] chemistry of nitro-alkenes and nitronates has been developed by Denmark et al. as a general approach to functionalized pyrrolidine-containing structures [118]. Within the subclass of inter [4 -I- 2]/intra [3 + 2] cycloadditions, they have documented the fused mode (/3-tether, Eq. 77), spiro mode (a-tether, Eq. 78), and bridged mode (a-tether, Eq. 79 or /3-tether, Eq. 80) constructions. These are highly stereoselective processes in the presence of Lewis acid such as SnCU and are amenable to asymmetric modification by use of chiral vinyl ethers. Finally, the nitroso acetals are readily transformed, by hydroge-nolysis, into polycyclic, a-hydroxypyrrolidinones, 4-aminocyclohexanones, and cyclo-pentylamines. 

As a consequence, the pyrrolidine derivative IV will be produced in as much as the nucleophilic attack of nitrogen is restricted to the carbon atom bearing the propylamino chain (spiro mode) since the analogous interaction with the other tertiary cyclopropyl carbon (fused mode, see dotted arrow) should afford the unrecorded piperidine derivative V. In actual fact, the spiro mode generally prevails over the latter. 

The intramolecular nucleophilic opening of diactivated cyclopropanes by amino functions has been used by Danishefsky to develop new stereospecific routes to N-heterocycles. This intramolecular ring-opening can occur in a spiro or in a fused mode (equation 199). It is shown that the spiro mode, leading to five- or six-membered rings. 

The pyrrolizidine system (570) is formed when the phthalimidocyclopropane 568 is treated with hydrazine in hot methanol, releasing the amine moiety which undergoes spontaneous ring mutation in the spiro mode leading to 569 and 570 (equation 200)337,338 pyrroloindoline system (572) has been prepared in a similar fashion ... 

Danishefsky and co-workers have used activated cyclopropanes to promote intramolecular alkylation of an amino function, followed by lactam formation to provide a new entry to the pyrrolizidine ring system.20 This route is outlined in Scheme 1. Cyclopropanation of the phthalimido-olefin (19) was achieved with dimethyldiazomalonate in the presence of copper bronze. Treatment of the cyclopropane derivative (20) with hydrazine released the amine, which gave the lactam ester (21) in quantitative yield. This corresponds to intramolecular homoconjugate addition entirely in the spiro mode.21 It seems reasonable that the first step in this process is internal alkylation of the amine by the activated cyclopropane. The alternative... 

Intramolecular nucleophilic attack in the activated cyclopropane (456) may proceed in a spiro mode or a fused mode, and the factors controlling the direction of ring-... 

These intramolecular homoconjugate additions provide a simple entry into fura-noid systems. The p-keto-ester (461) cyclizes in a spiro mode to (462a), whereas with dimsylsodium the isomer (462b) is formed. Similarly, the keto-ester (463 R = COjMe) is cyclized to (464) by sodium hydride, but the ketone (463 R = H) affords only the Dieckmann product (465) under these conditions. ... 

With the next lower member of this series with which the spiro mode could lead to a three-membered ring and the fused mode to a four-membered... 

The spiro mode is also favored in the ring opening of cyclic halonium ions. Thus the kinetically controlled products of the reactions of the 3-butenoate ion with bromine and iodine under carefully controlled conditions are j -lactones, which are presumably formed from cyclic bromonium and iodonium ions [Eq. (6)]. ... 

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