Amino-Cope rearrangement

Electronically rich 1,3-butadienes such as Danishefsky s diene react with chromium alkenylcarbene complexes affording seven-membered rings in a formal [4S+3C] cycloaddition process [73a, 95a]. It is important to remark on the role played by the metal in this reaction as the analogous tungsten carbene complexes lead to [4S+2C] cycloadducts (see Sect. 2.9.1.1). Formation of the seven-membered ring is explained by an initial cyclopropanation of the most electron-rich double bond of the diene followed by a Cope rearrangement of the formed divinylcyclopropane (Scheme 65). Amino-substituted 1,3-butadienes also react with chromium alkenylcarbene complexes to produce the corre-... 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

The Rh2(DOSP)4 catalysts (6b) of Davies have proven to be remarkably effective for highly enantioselective cydopropanation reactions of aryl- and vinyl-diazoacetates [2]. The discovery that enantiocontrol could be enhanced when reactions were performed in pentane [35] added advantages that could be attributed to the solvent-directed orientation of chiral attachments of the ligand carboxylates [59]. In addition to the synthesis of (+)-sertraline (1) [6], the uses of this methodology have been extended to the construction of cyclopropane amino acids (Eq. 3) [35], the synthesis of tricyclic systems such as 22 (Eq. 4) [60], and, as an example of tandem cyclopropanation-Cope rearrangement, an efficient asymmetric synthesis of epi-tremulane 23 (Eq. 5) [61]. 

In addition to a-allenic a-amino acids, the corresponding allenic derivatives of y-aminobutyric acid (GABA) have also been synthesized as potential inhibitors of the pyridoxal phosphate-dependent enzyme GABA-aminotransferase (Scheme 18.49) [131,138-142]. The synthesis of y-allenyl-GABA (152) and its methylated derivatives was accomplished through Crabbe reaction [131], aza-Cope rearrangement [138] and lactam allenylation [139], whereas the fluoroallene 153 was prepared by SN2 -reduc-tion of a propargylic chloride [141]. 

TV-Glycosyl homoallylamines have been shown to undergo a stereocontrolled Lewis acid-catalyzed aza-Cope rearrangement to produce chain-extended amino sugars85. The reactions proceed in good to excellent yields with high stereoselectivity. Schiff base... 

The SnCU-catalysed Claisen and Cope rearrangements of A -allylanilines and N-allylenamines, and the effect of meffl-substituents in the aromatic ring on the Claisen aromatic amino rearrangement of a series of fluorinated anilines, have been investigated. 

Scheme 8 Synthesis of the amino-allenylidene complex 32 through a [3,3] Aza-Cope rearrangement...

The use of a cationic aza-Cope rearrangement in concert with a Mannich cyclization has also been applied to the total synthesis of enantiomerically pure (—)-crinine (359) (205). In the event, nucleophilic opening of cyclopentenoxide with the aluminum amide that was formed on reaction of (/ )-a-methylbenzyl-amine and trimethylaluminum gave the amino alcohol 485 together with its (15,25) diastereomer. Although there was essentially no asymmetric induction in this process, the diastereomeric amino alcohols were readily separated by chromatography, and the overall procedure therefore constitutes an efficient means for the preparation of enantiomerically pure 2-amino alcohols from epoxides. When the hydrochloride salt derived from 485 was treated with paraformaldehyde and potassium cyanide, the amino nitrile 486 was formed. Subsequent Swem oxida-... 

The Claisen and Cope rearrangements are of great importance in both theoretical and synthetic organic chemistry and do not need an introduction81. When an amino group substitutes an allyl vinyl ether or a 1,5-hexadiene, the rearrangements lead to some interesting results. 

The preparation of other y-allenic amino acids by the aza-Cope rearrangement is described (1). 

Collaboration has played a consistent role in his research. His first collaborative project was with Professor Bob Moss, who approached Houk about help in interpreting carbene selectivity. Houk recalls a collaboration with Professor A1 Meyers concerning a failed anionic amino-Cope rearrangement. He had this reaction that didn t work and we did some calculations to explain why, he remembers, and this appeared as a JACS communication. Then for some time afterwards, A1 and others would call to say Hey, I ve got this reaction that doesn t work Can we get a JACS conununication ... 

Deloisy, S, Kunz, H, A novel synthesis of chain-extended amino sugar derivatives through Aza-Cope rearrangement of A-galactosyl-A-homoallylamines, Tetrahedron Lett., 39, 791-794, 1998. 

A further aspect of the generality of Claisen-type rearrangements is that the oxygen atom can be replaced by nitrogen or sulfur, leading to the amino- or thio-Claisen variants. They can also be viewed as hetero-Cope rearrangements, so that the amino-Claisen is also known as a 3-aza-Cope rearrangement (Scheme 71). 

Allin, S. M., Baird, R. D., Lins, R. J. Synthetic applications of the amino-Cope rearrangement enantioselective synthesis of some tetrahydropyrans. Tetrahedron Lett. 2002, 43, 4195-4197. 

Castelhano, A. L., Krantz, A. Allenic amino acids. 1. Synthesis of y-aiienic GABA by a novei aza-Cope rearrangement. J. Am. Chem. Soc. 1984, 106, 1877-1879. 

However, the most typical transformation of A-allylanilines is the [3,3]-sigmatropic rearrangement, known as the amino-Claisen rearrangement (46 - 47 48) that has been described in many reviews67-70 (equation 20). This process is sometimes also called the aza-Claisen rearrangement 71 as well as the aromatic aza-Cope rearrangement 72. 

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