Alcohol Pauson-Khand reaction

Also alkynylcarbene complexes can react as Michael acceptors with nucleophiles, forming 1,3-dien-l-ylcarbene complexes (Figure 2.17). Both carbon nucleophiles, such as, e.g., enamines [246-249], and non-carbon nucleophiles, such as imidates [250], amines [64,131,251], aliphatic alcohols [48,79,252], phenols [252], and thiols [252] can add to the C-C triple bond of alkynylcarbene complexes. Further reactions of the C-C triple bond of alkynylcarbene complexes include 1,3-dipolar [253,254], Diels-Alder [64,234,238,255-258] and [2 -i- 2] cycloadditions [259 -261], intramolecular Pauson-Khand reactions [43,262], and C-metallation of ethynylcarbene complexes [263]. 

Other solid-phase preparations of carbonyl compounds include the hydrolysis of acetals (Table 12.4), inter- [52] and intramolecular Pauson-Khand reactions, the isomerization of allyl alcohols, and the a-alkylation and a-arylation of other ketones. Tietze reported the generation of acetoacetyl dianions on cross-linked polystyrene and their selective alkylation at C-4 (Entry 6, Table 12.4). The use of weaker bases resulted in single or twofold alkylation at C-2 [53]. 

Alkenyl alcohols, into tj3-allyl palladium complexes, 8, 365 u-Alkenyl-aldehydes, in Ti-promoted Pauson-Khand reactions, 4, 270... 

In terms of functional group compatibility, ethers, alcohols, tertiary amines, acetals, esters, amides and heterocycles are compatible with the Pauson-Khand reaction. In the intramolecular version, relatively few carbon skeletons undergo the cyclization. Most intramolecular PKRs use systems derived from hept-l-en-6-yne (6) or propargyl allyl ethers (7) or amines (8). Other interesting and more recent substrates are enynes connected through aromatic rings like 9-11, which have allowed us and other groups to obtain aromatic polycycles (Fig. 1) [28-31]. 

The Pauson Khand reaction is compatible with a wide variety of functionalities, such as ethers, alcohols, tertiary amines, thioethers, ketones, ketals, esters, tertiary amides, carbamates, and benzene, furan, and thiophen rings. Disubstituted alkynes, alkenes with bulky allylic substituents, and trisubstituted alkenes frequently afford reduced yields of products. Because of the reduced ability of sterically hindered alkenes to coordinate and undergo insertion, insertion of one or more molecules of alkyne occurs instead. 

From alcohols. Alcohols can be transformed into phenylselenides in a stepwise manner via mesylation and reaction with lithium phenylselenolate. This procedure offers obvious advantages over the formation of the corresponding bromides or iodides when subsequent reaction with strong nucleophiles, such as organolithium compounds, are necessary to prepare the radical precursors. The diol 8 is converted to the bis(phenylselenide) 9 via the corresponding bis(mesylate) as shown in Scheme 2 [6]. Compound 9 is converted to the radical precursor 11 via reaction with lithium phenylacetylide followed by alkylation with allylbromide and a Pauson-Khand reaction. Such a reaction sequence would not be feasible with an alkyl halide. The cyclization afforded the expected tricyclic compound 12 in 95% yield. 

Pauson-Khand Bicyclization. Alkynyl and enol ether derivatives have been studied in the cobalt-mediated intramolecular Pauson-Khand reaction and found to provide high diastere-oselectivity, superior to previous work with the auxiliary 2-phenylcyclohexanol. The 3-substituted auxiliary alcohol (3) provides higher selectivity than the 2-substituted analog. Also, the alkynyl ether derivatives exhibit higher reactivity and selectivity than the corresponding enol ether derivatives (eq 6). 

Recent Developments in the Pauson-Khand Reaction Oxidative Rearrangement of Tertiary Allylic Alcohols Other Methods... 

Intramolecular Pauson-Khand reactions are often regioselective because it is physically impossible for the molecule to cyclise any other way. Pauson-Khand disconnection of bicyclic 111 reveals an allyl ether 112 of the alcohol 113, easy to make from acetylene and cyclohexanone. In the cobalt-catalysed cyclisation, only one regioisomer is possible and this, the TM111, is formed in an excellent 80% yield.28... 

Ester-based chiral auxiliaries have also beat used in other settings. P-Alk-oxyesters 1.27 of (R)-1 -phenylethanol 1.1 (R = Me, Ar = Ph) or (5)-1-naphthyl-ethanol 1.1 (R = Me, Ar = 1-Np) are transformed into dural synthons by reactions with a lithiated carbanion a to phosphorous followed by hydrogenolysis [194], Ethers 1.28 of chiral alcohols 1.1 undergo selective alkylations or hydroxyalkyla-tions [169]. The auxiliaries can be removed by hydrogenolysis. Enol or dienol ethers 1.29 and 1 JO suffer [2+2] [195, 196] or [4+2] cycloadditions [49, 197,198, 199], The best stereoselectivities are obtained when the chiral auxiliary is 1.1 (R = r-Pr, Ar=Ph), 1.4 (R=Ph), 1.5 (R = Ph), 1.10 or 1.13. These auxiliaries are cleaved either by acid treatment [199] or by other means in subsequent steps. Acetylene ethers G OC=CR derived from 1.5 (R=Ph) [199a] can undergo stereoselective Pauson-Khand reactions [200, 201], The auxiliaries are removed by treatment of the products with Sml2 in THF-MeOH. 

The alkyne-Co2(CO)6 complexes 1 are the binuclear cluster complexes of the acetylenic derivatives with the hexacarbonyldicobalt moiety. These complexes can be readily prepared by treatment of alkynes with commercially available octacarbonyldicobalt [Co2(CO)g] and can regenerate the parent triple bond functionality under some mild oxidation conditions. Two synthetically very useful reactions have so far been developed by taking advantage of the characteristic properties of the alkyne-Co2(CO)6 complexes 1 one is so-called Nicholas reaction" and the other is so-called Pauson-Khand reaction (Scheme 1). The alkyne-Co2(CO)6 complexes 1 possessing a hydroxyl group or its equivalent at carbon p- to alkyne moiety (propargyl alcohol derivatives) could easily... 

Since the targeted streptazolin-related natural products have a C2-unit at the C6-position, we first prepared the 2-oxazolone-alkyne derivative 82 with the simplest C2-unit, an ethyl group, at the triple bond terminus to not only identify suitable ring-closing conditions, but also to determine the level of stereoselectivity that could be expected in the intramolecular Pauson-Khand reaction. Thus, the 2-oxazolone-alkyne derivative 82, required for the intramolecular Pauson-Khand reaction in our retrosynthesis, was easily prepared from the known alcohol 78 by conventional means, as shown in Scheme 18. Oxidation of 78 was... 

Allenamides are functionalized at the a-position by virtue of the regioselective lithiation. Thus, on introduction of an alkynyl chain, valuable precursors of the Pauson-Khand reaction can be prepared. Lithiation of the silyl ethers of propargyl or allenyl alcohols engenders O —>C transsilylation. ... 

---