Intramolecular cycloadditions diazoalkanes

The synthesis of longifolene in Scheme 13.30 commenced with a Birch reduction and tandem alkylation of methyl 2-methoxybenzoate (see Section 5.6.1.2). Step C is an intramolecular cycloaddition of a diazoalkane that is generated from an aziridinoimine intermediate. 

Considerably better yields are obtained when the alkene is significantly strained, as in the synthesis of [3]peristylane (5). Note in this case that flash-vacuum pyrolysis is the method of choice for the final step. The intramolecular addition step in the synthesis of ( —)-cyclo-copacamphene (8) and in a very similar synthesis of (+ )-cyclosativene presumably also gain assistance from ring strain. It should be noted that in these last two syntheses, the diazoalkane-alkene intramolecular cycloaddition succeeded where attempted carbene-alkene cycloadditions had failed. 

Optically active 3-lactones are readih p using 72 as the chirality inducer. - - The p acids. The [2 -f 2]cycloaddition of ketenes ai nine leads to numerous c y-2,3-disubstituted f Reports on the advances of asymmetric 1 of diazoalkanes to A-(2-alkenoyl)oxazolidin-. 73, showing cooperative chiral control by the ral ligand.An intramolecular cycloaddition a chiral cyclic A,N -dimethylaminal unit ad>i 74) proves very successful in the asymmetric nitrone lacks stereoselectivity, - ... 

Reports on the advances of asymmetric 1,3-dipolar cycloadditions include the reaction of diazoalkanes to 7V-(2-alkenoyl)oxazolidin-2-ones catalyzed by Mg or Zn complexes of 73, showing cooperative chiral control by the achiral oxazolidinone auxiliary and the chiral ligand.An intramolecular cycloaddition of the same kind from substrates containing a chiral cyclic AiA -dimethylaminal unit adjacent to the dipolarophilic double bond (i.e., 74) proves very successful in the asymmetric sense, although the reaction of an analogous nitrone lacks stereoselectivity. 

The nonsymmetrical quinolizidine 373 was obtained from the acyclic symmetrical precursor 372 by means of a reaction sequence comprising azide formation, intramolecular 1,3-dipolar cycloaddition, thermal triazoline fragmentation to a diazoalkane, and Michael addition individual steps, as shown in Scheme 85 <2005CC4661>. 

Cyclohexadiene 45 was converted to 46 by what has proven to be a general method for preparation of the cyclohexa-2,4-dien-l-one ring system.2 Fragmentation of the aziridinyl imine in 46 at 110 °C gave an intermediate diazoalkane which underwent an intramolecular 1,3-dipolar cycloaddition to give the pyrazoline 47. At 140 °C, pyrazoline 47 expelled N2 and rearranged to the tricyclic ketone 48. The development of this and related bicyclizations29 illustrated a practical synthetic equivalence of an intramolecular diene-carbene 4-1-1 cycloaddition in the cyclohexa-2,4-dien-l-one series. 

The intramolecular [3 - - 2] cycloaddition reaction of diazoalkane 252 (Scheme 8.60) is remarkable for its high asymmetric induction. Due to the presence of the... 

In a novel total synthesis of the tricyclic sesquiterpene (—)-longifolene, an intramolecular diazoalkane cycloaddition to a cyclohexadienone ring followed by thermal ring contraction of the resulting pyrazoline gave the tricychc vinylcyclo-propane 261 and this constitutes the key steps in this synthesis (314) (Scheme 8.63). The interesting features of this sequence are the separation of dipole and dipolarophile by five atoms and the formation of a seven-membered ring in the cycloaddition step. 

Compounds with a Si=Si or Ge=Ge bond (i.e., disilenes and digermenes) can be isolated when the double bond contains bulky substituents. Only a few cycloaddition reactions with diazo compounds are known, and two reaction modes have been observed. One of the paths leads to the formation of disiliranes 184 (242) and digermiranes 185 (243) (Scheme 8.42), probably by ring contraction of an initially formed [3 + 2] cycloaddition product. The other path involves a 1,1-cycloaddition of the diazoalkane to give disilaaziridine 186 (244) and digermaazir-idine 187 (245). This nitrene-like reactivity is rather uncommon although some intramolecular examples are known (see Section 8.6.1). 

RC=CKWG) yields 2,4-di-EWG-substituted pyrroles in the presence of copper catalyst but 2,3-di-EWG-substituted pyrroles in the presence of a phosphine catalyst.74 The 3 + 2-cycloaddition of diazoalkanes to (6 )-3-p-tolylsulfinylfuran-2(5//)-one produces diastereoisomeric pyrazolines in almost quantitative yield and with des >98%. (g) The sulfinyl group is responsible for the complete control of the n-facial selectivity in all these reactions.75 The Rh(II)-catalysed intramolecular 1,3-dipolar cycloaddition reaction of diazoamides (57) with alkenyl and heteroaromatic n -bonds yields pen-tacyclic compounds (59), via the ylide (58), in good to excellent yields and in a (g) stereocontrolled manner (Scheme 15).76... 

The other major limitation to the route is the problem of obtaining the desired precursor. Since this determines the scope of the reaction we will follow the pattern set in Houben-Weyl, Vol.4/3 and consider the syntheses according to the route by which the five-membered-ring diazene was derived, namely from (1) the addition of diazoalkanes to acyclic alkenes and allenes (2) the addition of diazoalkanes to cyclic alkenes and heterocyclic compounds (3) intramolecular addition of diazoalkanes to double bonds (4) cycloaddition reactions of dialkyl... 

Using diazoalkanes results in the formation of isomeric mixtures of cycloadducts.Unlike some reactants (phenyl azide, tosyl azide and diphenylnitrilimine), benzonitrile oxide, diazomethane, and A-phenylbenzylideneamine A-oxide underwent [3 4- 2] cycloaddition on mixing with lumisantonin using A -phenylbenzylideneamine A-oxide, however, gave the product cycloadduct in 8% yield.Dihydropyrazoles were obtained in some cases.Furthermore, pyrrole derivatives were obtained in low yield by intramolecular addition of an azomethine ylide to an a- and / -monocyclopropyl acrylate moiety. 

The recent reviews on intramolecular cyclizations of diazoalkanes (Tsuge et al., 1989 Wade, 1991) do not include information on 1,5- and 1,7-dipolar cycloadditions. 

A similar intramolecular [l,l]cycloaddition of a 1,3-dipole is observed in the formation of (220) (86%) upon treatment of the diazoalkane precursor (219) with base (NaH) other examples of this reaction are described, and in one case the intermediate diazoalkane was isolated and separately transformed into a homopyrazole. ... 

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