The nitrosocarbonyl hetero-Diels-Alder reaction as a useful tool for organic syntheses

Abstract

Organic transformations that result in the formation of multiple covalent bonds within the same reaction are some of the most powerful tools in synthetic organic chemistry. Nitrosocarbonyl hetero-Diels-Alder (HDA) reactions allow for the simultaneous stereospecific introduction of carbon-nitrogen and carbon-oxygen bonds in one synthetic step, and provide direct access to 3,6-dihydro-1,2-oxazines. This Review describes the development of the nitrosocarbonyl HDA reaction and the utility of the resulting oxazine ring in the synthesis of a variety of important, biologically active molecules.

Figure 1

Examples of C-nitroso compounds.

Figure 2

Resonance stabilization of X–N=O compounds.

Figure 3

Examples of nitroso compounds with heteroatoms.

Figure 4

s-cis and s-trans Isomers of nitrosocarbonyl compounds.

Figure 5

Computed energies for transition states of the nitroso HDA reaction.

Figure 6

Examples of chiral nitrosocarbonyl compounds.

Figure 7

Other chiral nitrosocarbonyl species.

Figure 8

Examples of chiral acylic dienes.

Figure 9

Representative carbocylic nucleosides.

Figure 10

Structures of the tropane alkaloid family.

Figure 11

Structures of amaryllidacea alkaloids.

Figure 12

Representative amino acid derivatives and related structures.

Figure 13

Representative indolidizine and pyrrolidizine alkaloids.

Figure 14

Type I and type II intramolecular nitrosocarbonyl HDA reactions.

Scheme 1

The nitroso hetero-Diels–Alder reaction.

Scheme 2

Common synthetic routes to nitrosocarbonyl species.

Scheme 3

Reactions of nitrosocarbonyl compounds.

Scheme 4

Other reactions of nitrosocarbonyl compounds.

Scheme 5

The cycloaddition reported by Kirby and Sweeny.^[31]

Scheme 6

General selectivity observed for unsymmetrical dienes.

Scheme 7

Examples of regioselectivity in nitrosocarbonyl HDA reactions. TBS =tert-butyldimethylsilyl.

Scheme 8

Stereoselective nitrosocarbonyl HDA reaction in the presence of a chiral diene. Cbz =benzyloxycarbonyl.

Scheme 9

Catalytic asymmetric pyridylnitroso cycloaddition.

Scheme 10

Nitrosocarbonyl HDA reaction on a solid phase.

Scheme 11

Another nitrosocarbonyl HDA reaction on a solid phase.

Scheme 12

Modification of bicyclic 3,6-dihydro-1,2-oxazines.

Scheme 13

[3+2] Cycloaddition for the synthesis of 3,6-dihydro-1,2-oxazines. Tr =triphenylmethyl.

Scheme 14

Pyrrole synthesis by reductive cleavage of a N–O bond. Boc =tert-butoxycarbonyl.

Scheme 15

Enzymatic resolution of a racemic alcohol.

Scheme 16

An alternative method for cleavage of the N–O bond. Troc =trichloroethoxycarbonyl, Ts =toluene-4-sulfonyl.

Scheme 17

Lewis acid mediated cleavage of a C–O bond. Bn =benzyl.

Scheme 18

Brønsted acid mediated cleavage of a C–O bond. TfOH = trifluoromethanesulfonic acid.

Scheme 19

Cleavage of a C–O bond with Grignard reagents.

Scheme 20

An unusual reaction with a Grignard reagent.

Scheme 21

Pd/In-mediated cleavage of a C–O bond.

Scheme 22

Examples of alkene modification of bicyclic cycloadducts. Bz =benzoyl.

Scheme 23

[3,3] Rearrangment of an ergosteryl cycloadduct.

Scheme 24

Synthesis of the carbocyclic uracil polyoxcin C.

Scheme 25

Synthesis of azacarbocyclic nucleoside analogues., dba = trans,trans-dibenzylideneacetone, TBAD =di-tert-butyl azodicarboxylate.

Scheme 26

Synthetic route to pyrrolidines. NMO =4-methylmorpholine N-oxide, Tol =tolyl.

Scheme 27

Route to aza sugars from 1,2-dihydropyridines.

Scheme 28

General synthetic route to tropane alkaloids.

Scheme 29

Total synthesis of (−)-epibatidine.

Scheme 30

Synthetic route to narciclasine.

Scheme 31

Synthetic route to (+)-streptazolin.

Scheme 32

A nitroso-Diels–Alder reaction with piperine (177). TFA = trifluoroacetic acid.

Scheme 33

Thebaine analogues from an unexpected ring cleavage.

Scheme 34

General route to monocyclic alkaloids.

Scheme 35

Synthesis of (+)-azimine and (+)-carpaine.

Scheme 36

Total synthesis of (−)-lepadins A, B, and C. MOM = methoxymethyl, TBDPS =tert-butyldiphenylsilyl.

Scheme 37

Total synthesis of (+)-loline. PMB =para-methoxybenzyl.

Scheme 38

A recent example of a type II intramolecular nitrosocarbonyl HDA reaction.