Enol phosphates alkenes

Given the large number of tandem cyclization processes that have been explored [63], it is disappointing to note that so few have been promoted electrochemi-cally. There appears to be a significant opportunity for additional exploration. Two tyiws of tandem cathodic cyclizations are discussed below. The first involves generation of a ketyl, and its subsequent cyclization onto a pendant alkene to afford a new radical that closes onto a second alkene [64,65]. The second focuses on chemistry not yet discussed involving the reductive cyclization of enol phosphates of 1,3-dicarbonyl compounds [66]. 

The reductive cyclization of readily available enol phosphates of 1,3-dicarbonyl compounds bearing pendant olefinic units has been explored [66,67]. The chemistry is exceptionally interesting, and provides a unique route to structures possessing a cyclopropyl unit which is suitable for structural elaboration. The reaction occurs in a manner wherein the phosphate-bearing carbon behaves like a carbene that adds to the pendant alkene to form a cyclopropane. While this provides a useful way of viewing the transformation, mechanistic studies indicate that a carbene is not an actual intermediate. Examples are portrayed in Table 11. 

The opportunity for tandem cyclization was explored. Here, the results can be accommodated by postulating the intermediacy of a vinyl radical [66]. For example, the controlled potential reduction of enol phosphate 246 affords 247 as a mixture of stereoisomers, in addition to a 15% yield of the linearly fused tricyclopentanoid 248. Assuming that the initial reduction cleaves the phosphate unit, then there exists the opportunity for the resulting radical 249 to be further reduced to afford a carbanion, or undergo a 5-exo-trig radical cyclization onto the pendant alkene. Given the nature of the products and the fact that they are inconsistent with the expectations of carbanion chemistry, it seems clear that the latter pathway dominates. 

Enol phosphates may be reduced to alkenes,79 eliminated to alkynes,80,81 employed as synthetic intermediates in organophosphorus chemistry and are useful in their own right, for example, as insecticides. For reviews covering enol phosphates and the Perkow reaction, see Refs 17, 82, and 83. 

Deoxygenation of phenols. The reduction of enol phosphates to alkenes by titanium metal (8,482) has been extended to reduction of aryl diethyl phosphates to arenes. Yields are in the range 75-95% reduction with lithium in liquid ammonia (1, 248) usually proceeds in low yield. 

Appropriate quenching of a reductively formed lithium enolate with a carboxylic acid anhydride, chloride, methyl chloroformate or diethyl phosphorochloridate yields the corresponding enol esters, enol carbonates or enol phosphates. These derivatives may be transformed into specific alkenes via reductive cleavage of the vinyl oxygen function, as illustrated by the example in Scheme 8. 

Highly reactive metallic titanium, prepared from TiCb and potassium, reduces enol phosphates to alkenes, permitting regioselective synthesis of dienes from a,p-unsaturated ketones. ... 

This reaction sequence produces alkenes in a stereospecific manner, since the double bond geometry of the enol phosphate is retained in the alkene product. Furthermore, the newly formed alkene may be introduced in a regioselective fashion via trapping of the regioselectively formed enolate. ... 

Both the enol phosphate method, and the reduction of the keto sulfone to the p-hydroxy sulfone followed by reductive cleavage to produce ( )-alkenes, have been applied to the synthesis of brefeldin A. Gais and cowoikers added the sidfone (462) to the lactone (461), formed the enol phosphate and reduced with sodium and ammonia to the ( )-alkene (463), in a 65% overall yield (equation 107). ... 

Treatment of enolates with (R0)2P(0)C1 also results in 0-trapping to yield the corresponding enol phosphates. Dissolving metal reduction of enol phosphates is a useful procedure for the deoxygenation of ketones with concomitant, regiospecific formation of the alkene. ... 

A connective synthesis of alkynes inspired by the Julia alkenation was developed by Lythgoe and coworkers for the synthesis of la-hydroxy vitamin D3, as shown in Scheme 34. The P-keto sulfone (101) derived by condensation of the the metalated sulfone (99) with the ester (100) was converted to the enol phosphate (102), which on reductive elimination gave the enynene (103). 

The precise conditions for the reductive elimination are important. Use of Na(Hg) in THF-MeOH or THF alone gives messy reactions, owing to substantial cleavage of the P—O bond of the enol phosphate but this can be avoided with Na(Hg) in THF-DMSO. Alternatively, Na in liquid ammonia can be used to effect the reductive elimination but the reaction must be very carefully controlled in order to avoid reduction of the alkyne to a tra/ii-alkene. A deliberate over-reduction of the initial alkyne product to an alkene was used in a synthesis of the intermediate (104) in a synthesis of brefeldin (Scheme 35). ... 

Coupling of enol phosphates and alkylaluminum compounds.1 Enol phosphates and R3A1 couple in the presence of 3 mole % of this Pd(0) complex to give alkenes with retention of configuration. 

The Perkow reaction has been used to generate a wide range of vinyl phosphates. Reaction of trialkyl phosphites with a-halogeno-ketones provide vinyl phosphates.1-5 Alkenes are produced via reduction of the dialkyl enol phosphate using either sodium or lithium in liquid ammonia. 

Enone 69 is converted to the less substituted alkene 71 via the intermediacy of the enol phosphate 70.4 The sequence shown involves reduction with Li/NH3 (liquid) followed by phosphorylation of the resulting lithium enolates with diethyl phosphorochloridate to give 70, which is then treated with Li/EtNIVf-BuOH. Application of such methodology to steroid conversion has been reported by Ireland and Pfister41 and Kanata et al. 2... 

The FGH-ring system of the polyether toxin gambierol has been made as outlined in Scheme 26. Intermediate 130 was prepared from 2-deoxy-D-ribose in nine steps (sugar carbons numbered). Exocyclic alkene 131 was subjected to stereoselective hydroboration followed by a 5-alkyl Suzuki coupling with enol phosphate 132, also made from 2-deoxy-D-ribose, to give 133, which was further transformed to the FGH tricycle 134." ... 

Convenient new routes to tricyclo[4,1,0,0 ]hept-3-ene and its derivatives have been disclosed. Acetone-sensitized irradiation of bicyclo[3,2,0]hept-6-en-2-one affords the ketone (624), whose enol phosphate is reduced by lithium-ammonia to give the parent alkene (625). " A second route is also described, starting from the 7,7-di-bromonorcarane derivatives (626) and (627). Reaction of (626) with methyl-lithium in ether at 0°C afforded a 3 1 mixture of the tricycloheptenes (628) and (629) similar reaction of (627) gave (630 40%), but reactions of the parent dibromide were unsuccessful. Catalytic Ag ion causes the rearrangement of (628) and (629) to, respectively, 3-methyl- and 1-methyl-cycloheptatriene. Initial Ag" attack at the least hindered edge bond is implicated. Attempted preparation of the tetrahedrane dimer (631) by the addition of dibromocarbene to homobenzvalene followed by treatment of the adduct so obtained with excess methyl-lithium in ether at 0°C afforded instead 5-ethynyl-cyclohexa-1,3-diene. 

It was shown that a variety of readily available (Z) and ( )-enol phosphates are good stereoselective synthons. Thus as5unmetric epoxidation of these phosphates using Jacobsen s (Salen)Mn(ii) complex afforded a-hydroxy ketones in enantio-selectivity up to 96%. The reaction of enantiomerically enriched 2-methyl-2-nitro-3-(diphenylphosphatoxy)alkyl radicals (80) with tributyltin hydride and AIBN in benzene results in the formation of alkene radical/anion pairs (81) which are trapped intramolecularly, leading to pyrolidine and piperidine systems (82) with memory of stereochemistry (Scheme 17). ... 

P-Ketophosphonates are valuable intermediates in the realm of Homer-Emmons alkenation methodology. Acyclic variants are difficult to obtain from enol phosphates due to competing alkyne and allene formation. One solution utilized the dianion derived from a-bromo ketones and trapping with diethyl phosphorochloridate however, only moderate yields of P-keto phosphonates were reported. The most efficient procedure utilizes the anion derived from dialkyl methylphosphonate, addition to an aldehyde, followed by oxidation (eq 8). ... 

Phosphate groups can also be removed by dissolving-metal reduction. Reductive removal of vinyl phosphate groups is one method for conversion of a carbonyl compound to an alkene.224 (See Section 5.7.2 for other methods.) The required vinyl phosphate esters are obtained by phosphorylation of the enolate with diethyl phospho-rochloridate or /V A /V -tetramethyldiamidophosphorochloridate.225... 

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