Ring expansion cascade

The Buchwald group reported an interesting copper-catalyzed lactam /V-arylation/ ring-expansion cascade wherein compound 669 reacted with 2-azetidinone 670 in the presence of Cul and K2C03 to give 671 in 96% yield (Scheme 110) (04JA3529). 

The proposed reaction mechanism is shown in Scheme 6.75. The nitroalkene moiety of bifunctional ortAo-alkyne-substituted nitrostyrenes 159 is activated through hydrogen bonding with catalyst 160 to incorporate the stereoehemieal information in the first AFC reaction. Then the alkyne is activated under gold catalysis to affect the seeond AFC/ring expansion cascade. 

Cyclobutene derivatives (66) have been synthesized from a diyne and an alkene via a novel Au(I)-catalysed reaction. A highly active vinylidene intermediate (67), formed by a dual Au(I)-mediated activation of the diyne precursor, is believed to act as an alkylidene Au(I)-carbenoid to effect stereospecific cyclopropanation of the alkene the resulting methylenecyclopropane (68) converts to (66) via an Au(I)-catalysed ring-expansion cascade. 

Recently, further examples for dehydro Diels-Alder reactions were published, which are believed to proceed via intermediates of the type 205. To explain the formation of products besides those of the type 206, the authors [132] proposed a remarkable reaction cascade and supported it by quantum-chemical calculations. Accordingly, an isonaphthalene of the type 205 undergoes an electrocyclic ring expansion to give a l,2-dehydro[10]annulene derivative, in which a configurational isomerization occurs followed by an electrocyclic ring closure, yielding a further isonaphthalene of the type 205, and aromatization. 

This chapter covers the recent advances in amidocarbonylations, cyclohydrocarbonylations, aminocarbonylations, cascade carbonylative cyclizations, carbonylative ring-expansion reactions, thiocarbonylations, and related reactions from 1993 to early 2005. In addition, technical development in carbonylation processes with the use of microwave irradiation as well as new reaction media such as supercritical carbon dioxide and ionic liquids are also discussed. These carbonylation reactions provide efficient and powerful methods for the syntheses of a variety of carbonyl compounds, amino acids, heterocycles, and carbocycles. 

In this chapter, the recent advances in amidocarbonylations, cyclohydrocarbonylations, aminocarbonylations, cascade carbonylative cyclizations, carbonylative ring-expansion reactions, thiocarbonylations, and related reactions are reviewed and the scope and mechanisms of these reactions are discussed. It is clear that these carbonylation reactions play important roles in synthetic organic chemistry as well as organometallic chemistry. Some of the reactions have already been used in industrial processes and many others have high potential to become commercial processes in the future. The use of microwave irradiation and substitutes of carbon monoxide has made carbonylation processes suitable for combinatorial chemistry and laboratory syntheses without using carbon monoxide gas. The use of non-conventional reaction media such as SCCO2 and ionic liquids makes product separation and catalyst recovery/reuse easier. Thus, these processes can be operated in an environmentally friendly manner. Judging from the innovative developments in various carbonylations in the last decade, it is easy to anticipate that newer and creative advances will be made in the next decade in carbonylation reactions and processes. 

Jeff Auhc of the University of Kansas has reported (Org. Lett. 2004,6,4993) a cascade strategy of C-C and C-N bond formation. Thus, Diels-Alder cyclization of 11 and 12 gives 13, which in situ undergoes azido-Schmidt ring expansion to give 14. In a complementary approach, 15 and 16 combine to give 17 and then 18. 

Pattenden and Schulz have reported that treatment of the acetylene derivative 43 with (TMS)3SiH leads, in one pot, to the bicyclic compound 44 in 70% yield (equation 71)". The proposed mechanism involves (TMS)3Si radical addition to the triple bond to form a vinyl radical followed by a remarkable cascade of radical cyclization-fragmentation-transannulation-ring expansion and termination via ejection of the (TMS Si radical to afford the bicyclic product. 

A concise synthesis of the novel pyrrolo[l,2-a]benzodiazepine system 92, using the metallocarben-oid/spiro-[6,5]-ammoniumylide/Stevens[l,2]-shift with ring-expansion approach, was reported. The overall cascade process was stereospecific <07T12232>. 

Recent advances in the synthesis of trans-iused polycyclic ethers by hydroxy epoxide cyclization reactions via monocyclic epoxonium ion intermediates and ether ring expansion reactions via bicyclic epoxonium ion intermediates are described in a review by Fujiwara and Murai. Natural trans-iu eA polycyclic ethers (e.g., brevetoxin A and ciguatoxin), produced by marine sources such as dinoflagellates, are hypothesized to be constructed from the corresponding polyepoxide precursors by a cascade of ring-closure reactions, which has prompted much work in the development of new methods for the construction of cyclic ethers from epoxides <2004BCJ2129>. 

Ring expansion of cyclopropylcarbinol to cyclobutanol is the basis of an efficient cyclobutene synthesis (equation 25). An elegant approach to polycyclic hydrocarbons is realized by a cascade of cyclopropylcarbiny 1-cyclobutyl rearrangements (equation 26) . 

Mohamed, R. K., Mondal, S., Gold, B., Evoniuk, C. J., Banerjee, T., Hanson, K., Alabugin, I. V. (2015). Alkenes as Alkyne Equivalents in Radical Cascades Terminated by Fragmentations Overcoming Stereoelectronic Restrictions on Ring Expansions for the Preparation of Expanded Polyaromatics. Journal of the American... 

Nemeto, H., Yoshida, M., Fukumoto, K. and lhara, M. (1999) A novel strategy for the enantioselective synthesis of the steroidal framework using cascade ring expansion reactions of small ring systems - asymmetric total synthesis of (-l-)-equilenin. Tetrahedron Lett., 40, 907-10. 

Yoshida M, Ismail MAH, Nemoto H, Ihara M (2000) Asymmetric Total Synthesis of (+)-Equilenin Utilizing Two Types of Cascade Ring Expansion Reactions of Small Ring Systems. J. Chem Soc Perkin Trans I 2629... 

Pattenden, G. and Schulz, D.J. (1993) Cascade Radical Reactions in Synthesis. A New Radical Mediated Double Ring Expansion-Cyclization Process with Oxime Ethers, Tetrahedron Lett. 34, 6787-6790. 

Hollingworth, G. J., Pattenden, G. and Schulz, D. J. (1995) Cascade Radical Cyclization-Fragmentation-Transannular-Ring Expansion Reactions Involving Oximes. A New Approach to Synthesis of Angular Triquinanes, Aust. J. Chem. 48, 381-399. 

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