Nitroso compounds, chiral, asymmetric

Aliphatic and aromatic nitroso compounds are powerful dienophiles and react with a variety of acyclic, cychc and heterocyclic 1,3-dienes producing cyclic hydroxylamines. The reaction proceeds with a high regioselectivity at room temperature (equation 99 291-293 Asymmetric variation of the reaction with chiral copper-BINAP catalyst has been reported ". The cycloaddition is reversible and some amounts of diene and nitroso components may be observed in reaction products. 

In some recent investigations carried out by Streith s [346, 347] and Wyatt s groups [348], also chiral dienes turned out to exhibit noteworthy potential for asymmetric cycloadditions to achiral nitroso compounds. 

Ruthenium(II) complexes may also be used to oxidize N-Boc hydroxylamine in the presence of tert-butylhydroperoxide (TBHP) to the corresponding nitroso dieno-phile, which is subsequently trapped by cyclohexa-1,3-diene to give the hetero Diels-Alder adduct (Entry 1, Scheme 10.26) [51]. A triphenylphosphine oxide-stabilized ruthenium(IV) oxo-complex was found to be the catalytically active species. Use of a chiral bidentate bis-phosphine-derived ruthenium ligand (BINAP or PROPHOS) result in very low asymmetric induction (8 and 11%) (Entry 2, Scheme 10.26). The low level of asymmetric induction is explained by the reaction conditions (in-situ oxidation) that failed to produce discrete, stable diastereomerically pure mthenium complexes. It is shown that ruthenium(II) salen complexes also catalyze the oxidation of N-Boc-hydroxylamine in the presence of TBHP, to give the N-Boc-nitroso compound which can be efficiently trapped with a range of dienes from cyclohepta-1,3-diene (1 h, r.t., CH2CI2, 71%) to 9,10-dimethylanthracene (96 h, r.t., CH2CI2,... 

The well-established Diels-Alder reaction between nitroso compounds and conjugated dienes has continued to be refined over the last decade. The most important advances have been in the development of chiral nitroso dienophiles useful for asymmetric synthesis and in the exploitation of the intramolecular Diels-Alder reaction in synthesis <94S1107>. 

A number of examples have been reported of the asymmetric hetero Diels-Alder reaction of heterodienes or heterodienophiles such as imines, nitroso or carbonyl compounds.The chiral auxiliary is commonly attached to the nitrogen atom of the imine or nitroso compound, or a chiral ester or amide substituent may provide the necessary asymmetric induction. As an example, the a-cWoronitroso dienophile 132, bearing a sugar-derived auxiliary, has been found to be effective for the formation of cyclic hydroxylamines with high optical purity (3.95). The initial cycloadduct breaks down readily (see Scheme 3.32), via an iminium ion with subsequent methanolysis to release the chiral auxiliary and the product 133. 

Encouraging results were obtained in asymmetric cycloadditions of chiral dienes, which react readily with achiral nitroso compounds as outlined below. 

In another context, excellent enantioselective nickel-catalysed a-ami-nations of N-Boc-oxindoles with azodicarboxylates have been achieved by using chiral Schiff base nickel catalysts. BINAP ligands have also encountered success in asymmetric nickel-catalysed electrophilic a-aminations and also in combination with other metals such as palladium. On the other hand, the use of other sources of electrophilic nitrogen, such as nitroso compounds and iodinanes, in reactions catalysed by nickel has so far not been described. 

Vol. 28, p. 226, ref. 44 for related work). Similar cycloadditions of dienyl pyrrolidinones [le. AT-(peiita-l,3-dienyl)- or -(buta-l,3-dienyl)-pyrolidin-2-one] with the in situ generated acyl nitroso compound derived from benzyl-JV-hydroxy-carbamate with periodate have led to the preparations of racemic pyroUidines 56 and 57 (R = H or Me). The latter compound is thought to exist as a dimer. An asymmetric synthesis of l,S,6-trideoxy-l,5-imino-D-altritol in which the piperidine ring is formed from a pyiidinium ring bearing Seebach s oxazolidinone chiral auxiliary has also been described. ... 

Among the existing methods for the asymmetric synthesis of chiral a-hydroxy carbonyl compounds, the direct enantioselective a-aminoxylation of carbonyl compounds is one of the most important strategies to achieve this purpose. Although its nitrogen versus oxygen electrophihc reactivity in nitroso compounds should be carefully controlled through the election of appropriate catalysts and reaction conditions. 

Tandem pericyclic reactions are a powerful strategy for construction of complex, polycyclic compounds. In recent years tandem [4 + 2]/[3 + 2] chemistry of nitro-alkenes and nitronates has been developed by Denmark et al. as a general approach to functionalized pyrrolidine-containing structures [118]. Within the subclass of inter [4 -I- 2]/intra [3 + 2] cycloadditions, they have documented the fused mode (/3-tether, Eq. 77), spiro mode (a-tether, Eq. 78), and bridged mode (a-tether, Eq. 79 or /3-tether, Eq. 80) constructions. These are highly stereoselective processes in the presence of Lewis acid such as SnCU and are amenable to asymmetric modification by use of chiral vinyl ethers. Finally, the nitroso acetals are readily transformed, by hydroge-nolysis, into polycyclic, a-hydroxypyrrolidinones, 4-aminocyclohexanones, and cyclo-pentylamines. 

In analogy t 0 the Cu(II) complex systems, the silver(I) -catalyzed aldol reaction is also proposed to proceed smoothly through a Lewis acidic activation of carbonyl compounds. Since Ito and co-workers reported the first example of the asymmetric aldol reaction of tosylmethyl isocyanide and aldehydes in the presence of a chiral silver(I)-phosphine complex (99,100), the catalyst systems of sil-ver(I) and chiral phosphines have been applied successfully in the aldol reaction of tin enolates and aldehydes (101), Mukaiyama aldol reaction (102), and aldol reaction of alkenyl trichloroacetates and aldehydes (103). In the Ag(I)-disphosphine complex catalyzed aldol reaction, Momiyama and Yamamoto have also examined an aldol-type reaction of tin enolates and nitrosobenzene with different silver-phosphine complexes (Scheme 15). The catalytic activity and enantioselectivity of AgOTfi(f )-BINAP (2 1) complex that a metal center coordinated to one phosphine and triflate were relay on solvent effect dramatically (Scheme) (104). One catalyst system solves two problems for the synthesis of different O- and AT-nitroso aldol adducts under controlled conditions. 

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