Intramolecular Nicholas reaction using

Example 2, intramolecular Nicholas reaction using chromium ... 

Crisostomo, F. R. P., Martin, T., Martin, V. S. Stereoselective intramolecular Nicholas reaction using epoxides as nucleophiles. Org. Lett. 2004, 6, 565-568. 

The application of the intramolecular Nicholas reaction by C. Mukai et al. made it possible to develop a novel procedure for the construction of oxocane derivatives. Interestingly, several Lewis and Bronsted acids gave rise to complex mixtures. However, the use of mesyl chloride/triethylamine in refluxing DCM afforded the desired oxocane as the sole product. 

Bertrand recently generated six- and seven-membered rings using a terminal alkene nucleophile in exocyclic intramolecular Nicholas reactions. Depending on the nature of the Lewis acid, the carbocation intermediate formed upon cyclization (e.g., 46) could be converted into a halide, amide, ester, or alkene. For example, alcohol 45 undergoes a 6-e [Pg.293]

The most impressive use of a tandem strategy involving the Nicholas reaction in a total synthesis project is Schreiber s preparation of (+)-epoxydict5miene (61). Cobalt complexation of 58 followed by an endocyclic intramolecular Nicholas reaction with an allylsilane nucleophile yields Pauson-Khand precursor 59. Treatment of 59 with iV-methylmorpholine-iV-oxide (NMO) promotes the Pauson-Khand reaction to furnish tetracycle 60 which was ultimately converted to the target natural product 61. ... 

Later on, Schreiber used consecutively these two reactions in the key step for the synthesis of diterpene (-i-)-epoxydictimene (73), starting from natural (R)-pulegone [116,117]. This approach was built on their preliminary studies on Lewis acid mediated intermolecular Nicholas reactions [118]. They prepared functionalized enyne 70 bearing a mixed acetal. This compound was transformed into its dicobalt-hexacarbonyl complex and, in the presence of a carefully selected Lewis acid, it formed a stabilized carbocation by release of the more accessible ethyl moiety. This cation reacted intramolecularly with the allylsilane giving the central eight membered ring of the natural product... 

Intramolecular alkylation reactions employing allylsilanes have been developed. A taxoid bicyclo[9.3. l]pentadecane ring system was prepared via intramolecular alkylation of (150). It is interesting to note that the alkylation occurred in the y-position relative to the alkyne (Scheme 218). A Nicholas reaction was used in the synthesis of (+)-epoxydictymene (Scheme 219). 

An underused property of cobalt-coordinated alkynes is the stabilization of propargyllic cations. The Nicholas reaction is a propargylic substitution reaction facilitated by the ability of the adjacent cobalt complex to stabilize the propargylic cation, 67 to 68. Both carbon and heteroatom nucleophiles have been used to effect this transformation. " This transformation has been been used as a strategy to introduce the alkene component for an intramolecular PKR. Shea has probed the use of an... 

The Nicholas and Pauson-Khand reactions, as well as the bond-angle effect, have been combined in a single synthetic scheme to make more efficient use of the cobalt. This has been done in a synthesis of epoxydictamine 7.90 (Scheme 7.24)." The Nicholas reaction was employed, in which a carbocation 7.87, generated from acetal 7.86, was trapped by an allylsilane nucleophile intramolecularly, to form the eight-membered ring... 

The Nicholas reaction enables efficient substitution reactions of propargyl alcohols, ethers, and acetates. Prior to the substitution step, dicobalt octacarbonyl reacts with the alkyne to yield cobalt-alkyne complex 1. The resulting organometallic complex reacts with inter- or intramolecular nucleophiles in the presence of a Lewis or protic acid to furnish desired substitution products 2. The cobalt-complexed alkyne can be oxidatively removed after this step or used to further fiinctionalize the Nicholas reaction products. The stereoselective synthesis of chiral products using the title reaction is also possible. ... 

Since its discovery just over thirty years ago, the Nicholas reaction has become a highly useful tool for the organic chemistry community. Applications of the Nicholas reaction fall into four categories intermolecular reactions, endocyclic intramolecular reactions, exocyclic intramolecular reactions, and tandem reactions. For this discussion, endocyclic means that the cobalt-complexed alkyne is in the ring formed during the Nicholas reaction, while exocyclic indicates that the cobalt-alkyne complex is outside the newly generated ring. 

In addition to her studies on the asymmetric Nicholas reaction mentioned previously (13 14), Tyrrell investigated standard intramolecular cyclizations to generate benzopyrans. An important advance in this report is that Tyrrell performed the cobalt complexation, Nicholas reaction, and cobalt decomplexation using a one-pot procedure. The conversion of propargyl alcohol 48 into benzopyran 49 highlights this strategy... 

Propargylic radicals are generated on reduction of metal-complex-stabilized Nicholas cations with Zn. This principle, which has been found very recently [21], can be used for ring-closure reactions via intramolecular radical recombination [Eq. (12)]. 

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