Cascade cyclic compound synthesis

Silicon-Induced Domino Reactions. In a series of papers, Schaumann et al. disclosed the synthesis of various cyclic compounds utilizing a silicon-induced reaction cascade. Treatment of an epoxyalkyl tosylate with 2-lithio-2-TMS-l,3-dithiane leads to the corresponding lithium alkoxide. Subsequent 1,4-Brook rearrangement and displacement of the tosylates affords cyclopen-tanols in good yield (eq 24). ... 

Reaction of cyclic sulfates with intramolecular O-nucleophiles leads to cyclic ethers and other heterocycles (Table 1). For example, a hydrolysis of compound 39 has produced predominantly the cyclic alcohols 41 (Scheme 4) < 1995JA12873 >. When the reaction was buffered with pyridine, the sulfate ester 40 was isolated rather than the free alcohol. An alcohol function in an intermediate product may give a route to a polysulfate cascade cyclization, which has been successfully realized in the synthesis of poly(tetrahydrofurans) (Table 1) <1995JA12873>. 

The enantioselective synthesis of azabicyclic y-lactams starting from 2-azanorbornenones after treatment of a catalytic amount of RuCl2(PCy3)2 (= CHPh) in the presence of ethylene or allyl acetate proceeds also via ring rearrangement—alkene metathesis (ROM-CM-RCM) [41] (Scheme 19). If n = 0 or 3, no RCM occurs and a cyclic dialkenyl compound is formed by cascade ROM-CM reactions. 

In 1978, we reported the repetitive synthesis of noncyclic and cyclic (so called nonskid chainlike ) polyaza compounds, which were the first examples of cascade molecules (Scheme 1). Since that time, dendrimers have gained widespread attention in organic, as well as in inorganic2,3 and physical chemistry.4 In 1992, De Gennes received the Nobel prize in physics for his studies on chaos and fractals. His results are relevant for the molecular design of cascade polymers especially in their three-dimensional growth. 

Cyclic sulfites. 1,2-Diols form cyclic sulfites very readily. Although there are few important synthetic uses for these compounds, their oxidation to cyclic sulfates provides excellent substrates for nucleophilic substitutions. Tetrahydrofuran ring closure in an intramolecular attack has enormous implication for the synthesis of a family of natural products, because proper design can precipitate a cascade process. 

Two-component cascade reactions are of paramount importance in the synthesis of cyclic products. There are a lot of examples in organocatalysis dealing with different reactants and activation modes. We wiU try to summarize the most relevant ones. First, we will describe the synthesis of different carbocycles based on the ring size. Then we will focus on cascade reactions that render acyclic compounds. 

Similar to AAOs, MAO can also be employed either in the stereoinversion starting from an enantiopure amine or in the deracemization starting from the racemate vide supra) [18]. Both approaches have been proven to be remarkably efficient for chiral amine synthesis, in particular for cyclic secondary and tertiary structures. Conversely, for acyclic imine intermediates, a competing hydrolysis reaction toward the carbonyl compound is often observed, thus leading to a diminished product yield. This spontaneous hydrolysis was recently exploited for the deracemization cascade reaction combining an (S)-selective MAO with an (R)-selective co-TA (Scheme 2.44) [149]. 

In subsequent studies, the scope of the Heck reaction/ anion-trapping cascade was further extended using soft car-banionic nucleophiles as illustrated in the asymmetric synthesis of (—)-D -capnellene 17. Treatment of prochiral vinyl triflate 15 with Pd(OAc>2, (5)-BINAP, and NaBr, as weU as the sodium enolate of diethyl (2-((rert-butyldiphe-nylsilyl)oxy)ethyl)malonate, gave the cyclic product 16 in 87% ee and 77% yield as the sole product. The use of NaBr as an additive improved the optical yields and was critical in preventing counteranion exchange between the triflate anion and the enolate anion by complexing with sodium enolate (Scheme 13.6). Compound 16 was then advanced through several steps to complete the total synthesis (—)-D -capnellene 17. 

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