Propellanes reductive

The treatment of the double bridgehead sulfide, l,3-bis(phenylthio)bicyclo[l.l.l]-pentane (15d), with lithium 4,4 -di-/-butylbi phenyl also induces reductive elimination and leads to [l.l.ljpropellane71. However, as the required bicyclo[l.l.l]pentanes 15 are most conveniently prepared from the corresponding propellanes, they do not really offer an alternative synthetic route to [1.1. IJpropellanes. They are best considered as convenient propellane storage materials37. 

An elegant application of this photocycloaddition in the field of triquinane synthesis has been reported by Reddy and Rawal [160]. The initially formed oxetane 163, formed from the Diels-Alder adduct 162, is easily cleaved reductively (by use of LiDBB = lithium di-/er -butyl-biphenylide) to give 164. This approach was also used for the construction of structurally diverse di- and (propellane-type as well as linear or angular anellated) triquinanes [161]. The classic linear triquinane hirsutene is also available via this route [162]. Star-like molecules like the tiene 167 are available via a sequence of intramolecular photocycloaddition (from the 1,3-cyclohexadiene/acylallene adduct 165) and oxetane (166) ring-opening (Sch. 58) [163]. Further examples of intramolecular... 

The utilization of an optically active triazolinedione for asymmetric transfer has also led to the preparation of enantiomerically pure polycyclic hydrocarbons. The method provides a straightforward means for introducing optical activity into chiral propellanes that possess a conjugated diene unit. Racemic propellane reacts with (-)-enethyl acetate at —78 °C to give, after HPLC separation, the two optically pure urazoles. Subsequent reduction with lithium aluminum hydride affords the two propellanes in enantiomerically pure form (eq 3). 

Despite these modifications, Ireland s original method of both vinyl phosphate formation and reduction remains the most popular. In studies on the cationic rearrangements of [4.3.2]propellanes, Smith et converted a tricyclic ketone, via the diethyl vinylphosphate derivative, into the corresponding alkene (Scheme 26). In a similar manner, Kamata et al prepared A - and A -steroids (Scheme 27) with excellent control of regiochemistry. As shown in this example, esters are susceptible to cleavage under the standard reduction conditions (Li, NHa, Bu OH, -35 C), while acetals survive. 

Table 1 lists the experimental conditions for the electrochemical formation of a cyclopropyl ring from a variety of 1,3-dihaloalkanes, mostly from dibromoalkyl derivatives. A free cyclopropyl ring as well as a spiro derivative (entry 6), bicyclobutanes (entries 8-10) and other fused and highly strained systems such as tricyclene (entry 11) and a propellane derivative (entries 12,13) were obtained. In addition, Carroll and Peters have found evidence for the intermediacy of [2.2.1 ]propellane upon reducing 1,4-dihalonorbor-nanes electrochemically at a low temperature, although attempts to isolate it were unsuccessful. The intramolecular electrochemical reduction of a dihalo-substituted tricyclic compound leads to cyclization with formation of a tetracyclic derivative in which... 

The same authors showed that the same reaction, in principle, may give an unsaturated propellane, i.e. [4.4.1]propell-2-ene (5) whose reduction constituted the first synthesis of [4.4.1]propellane (6) itself. ... 

The reverse reaction from the dibromide to the propellane parent had already been reported by electrochemical means . The diiodide 74 gives [3.2.1]propellane with t-BuLi at - 77°C. Reduction of 72 and the dichloride 75 give 76. The length of the conjoining bond in 8,8-dichloro[3.2.1]propellane is 1.572 Its minimum strain energy was estimated to be 60 kcal mol" ... 

Electrolytic reduction of 1,4-dihalonorbornanes (81) at mercury electrodes in DMF provided evidence for the intermediacy of [2.2.1]propellane . Anomalously long-range... 

An electrochemical reductive cyclization (see Section II) affords [4.4.1]propellan-3-one (110) in unusually high yield . 

For the reduction of 1,4-dihalonorbornanes at platinum in DMF containing TEABr, Wiberg and coworkers [159] found that the products are norbornane and l,l -binorbornyl, but there was no evidence for the formation of [2.2.1]propellane. However, when 1,4-dihalonorbornanes are electrolyzed at mercury in DMF [169,170], the major products are norbornane and bis(l-norbornyl)mercury, along with a small amount of l,l -binor-bornyl, and it was concluded that [2.2.1]propellane is an intermediate. 

A combination of a photochemical [2 -i- 2] cycloaddition of dichloroethylene to enone (4), followed by a reductive elimination, was used to prepare the tricyclic cyclobutene (5), which served as a precursor to the highly strained 8-carboxy[6]paracyclophane (6 Scheme 2). A similar strategy has been used to prepare other strained propellanes. ... 

The diester (19) with sodium and TMS-Cl in an inert solvent gives the trimethylsilyl enediol ether, another propellane, in only 24-40%, together with 58-40% of the silylated compound (21), formed by reductive cleavage of the central bond (19 Scheme 15). ... 

The reduction of l,5-diiodobicyclo[3.2.1]octane with /ert-butyllithium proceeded rapidly at — 77°C to afford tricyclo[3.2.1.0 ]octane (1) in 59% yield.This [3.2.1]propellane is inert to the action of tert-butyllithium at room temperature. ... 

A less reactive bicyclo[3.2.0]hept-l(7)-ene substructure has been found in 164 (149). This compound was prepared from propellane 163 by photolysis and subsequent reduction. In contrast to 163, irradiation of the parent tricyclic ketone 165 in ethanol gives the saturated ketone 167. The formation of 167 is taken as evidence for the intermediate formation of the ketone 166. When 168 was treated with CsF in the presence of 1,3-diphenylisobenzofuran, an adduct was isolated, which was assigned the structure of the expected [2 + 4]cycloaddition product of 169 (150). 

We next examined the reactivity of the stable iminium ion 63a (Scheme 27). When the iminium 63a was treated with NaOAc or NaNs, only the starting material was recovered. The reaction of 63a with -BuLi or lithiated dithiane gave complex mixtures. The stronger basic nucleophiles, like -BuLi and lithiated dithiane, may attack both the iminium carbon (C23) and the hyperconjugated carbons (C5) to give complex mixtures (Fig. 17). However, the reduction of iminium 63a with NaBH4 afforded the saturated propellane derivative 69. The reaction of iminium 63a with NaCN ° provided nitrile 70 then reduction of the nitrile 70 produced amine 71 in a... 

A further, somewhat more efficient route to the propellane is the electrochemical reduction of the dibromide (195 X = Br) at relatively negative electrode potentials. Formation of the tricyclic hydrocarbon was again demonstrated by its trapping with halogen, the addition of chlorine giving a 12 % yield of (195 X = Cl) after 5 h reduction at -2.35... 

The thermal reaction, at room temperature, of A -bicyclo[2A0]hexene (277) gave, besides polymeric material, a dimer now identified as 2,5-dimethylenetricyclo-[4,2,2,0 ]decane (278). Reaction of (277) with irons, frans-dimethyl-2,5-hexadiene gave the olefin (279) and reduction of both (278) and (279) gave cis-2,5-dimethyltri-cyclo[4,2,2,0 ]decane. The reactive double bond in (277) differs from that usually associated with thermal olefin dimerizations. In most cases, such reactivity has been associated with double bonds which are torsionally strained. In (277) the torsion angle about the double bond must be zero and the reactivity must be associated with angular deformation at the olefinic carbons. Addition of ketene to (277) gave 3-methyl-6-methylenecyclohex-2-ene-l-one. In both reaction with ketene and dimerization, [2,2,2]propellanes would appear to be reasonable intermediates. 

Irradiation of bridgehead bromides and iodides (RX) in a variety of solvents (SH) results in the formation predominantly of the nucleophilic substitution products (RS) as well as some hydrocarbon (RH), particularly with the bromides. Both radical and heterolytic cleavage of the photoexcited RX molecules are encompassed within the mechanisms discussed. The systems studied include 1-norbornyl, 1-norbornylmethyl, and 1- and 2-adamantyl bromides and iodides. Electrochemical and metal-ammonia reduction of 1,4-dihalogenonorbornanes yields mainly nor-bornane (and not the required [2,2,l]propellane) and some l,r-bisnorbornane. ... 

Ramberg-Backlund reaction 568-571 leading to propellanes 569, 570 Raney nickel, for reduction of dithio-acetals 529-532 for reduction of monothioacetals 549... 

Modhephene, 34, was the first isolated propellane natural product. As such, the Weiss-Cook reaction was the perfect method for its construction. The process began with the condensation of 2 with diketone 27. Standard conditions for decarboxylation produced the core scaffold 28. Hydrogenation of the mono-enol phosphate afforded the monoketone 29. The cyclopropyl derivative 30 was prepared by copper-catalyzed decomposition of a diazoketone. gem-Dimethylation to generate 31 preceded carboxylation and esterification to afford the advanced intermediate 32. Cuprate-induced cyclopropane ring opening and methylation of the 3-ketoester introduced the final carbon atoms giving rise to 33. Lithium iodide induced decarboxylation preceded reduction of the ketone followed by dehydration with Martin s sulfurane, thus producing 34. 

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