Azabicyclic ketone

Similarly, chiral bases have found use in the preparation of building blocks for synthesis of alkaloids. A range of A-protected azabicyclic ketones was deprotonated to yield corresponding silylenol ethers (Scheme 30)68-70. The highest ee (93%) was obtained using 42 under internal quench conditions. These chiral ethers found use as key intermediates in the preparation of naturally occurring alkaloids. 

Yamada and Kunieda investigated the application of the octant rule to azabicyclic ketones and found good agreement of the predictions with the experimental results obtained for 1-oxopyrrolizidine of known chirality. ... 

An alternative and more direct procedure for the construction of the macrocyclic E ring from model AC azabicyclic ketones involves the stereoselective introduction of the required Z,Z-configurated eight-carbon chain in a single synthetic step, using the nonstabiUzed ylide derived from phos-phonium salt 115, which already contains the central C17—Cig Z-double bond and the ester functionality needed for the ring closure by a macrolac-tamization reaction" (Scheme 25). 

The azabicyclic ketone 114 was prepared from 4-vinylcyclohexene by the route summarized in Scheme 25, via azide 111 and the amino epoxide intermediate 112, which underwent a smooth in situ cyclization to amino-alcohol 113. 

An unexpected result from the same series of work as above by Perumal et al was obtained when cycloalkenones were used as dienophiles [187]. Instead of the imino Diels-Alder product, azabicyclic ketones were obtained (Figure 8.79). The authors proposed a novel Diels-Alder reaction between In-dienolate ions as dienes, and the imines as dienophiles. Another possibility brought up by the authors was that the products were the result of a tandem aldol reaction on the imine, followed by a Michael-type cyclization reaction. 

Reactions of this type are mostly performed with internal nucleophiles attached to the carbon atom adjacent to the iminium nitrogen, thus leading to tropane-like azabicyclic systems. Both allyl- and propargylsilanes, activated and unactivated alkenes, and ketones have been successfully used as nucleophiles. The products 1 and 2 are also obtained via two consecutive C —C bond-forming reactions in a single operation. 

Wiseman and Lee (1986) also reached the ketone 14 by a route involving the cyclization of 1,5-cyclooctanediol (16 Scheme 7.4). This transformation involved the Jones oxidation of 16 to give the hemiketal 17, which was transformed into the 9-methyl-9-azabicycle[3.3.1]nonan-l-ol 18 by treatment with methylamine, followed by addition of sulphuric acid (Quinn et al. 1973). This skeleton was reconverted into the 9-azabicyclo[4.2.1]nonane by bromination-reorganisation with pyri-dinium bromide perbromide in hot acetic acid in one direct step (Stjernlof et al. 1989). This constitutes the key step of this synthesis, affording the ketone 14 in 56% yield. 

Tautomerization with concomitant protonation of the bridgehead Nsp3 and the less basic Nsp2 nitrogen generation of an enol i, which is also an enamine, and C8 N + R3 heterolysis The pyridine-type heterocycle is an electron-attracting moiety as exemplified by the spontaneous low-temperature enolization of 1-azabicyclic [3.2.2]ketones 115 and 116 described below (Scheme 12.43). 

Of particular use is the reaction of [hydroxy(tosyloxy)iodo]benzene (HUB, also known as Koser s reagent) with ketones leading to a-tosyloxyketones [185-187], This is a highly chemoselective reaction different functional groups, aromatic rings and carbon-carbon double bonds are well tolerated under the reaction conditions [188], Scheme 3.59 shows a representative example of synthetic application of HUB for the functionalization of the azabicyclic alkaloid anatoxin-a, which is one of the most potent nicotinic antagonists. Specifically, the reaction of A-Boc anatoxin-a 140 with HTIB is the method of choice for the preparation of the synthetically versatile a-tosyloxy ketone 141 (Scheme 3.59) [189],... 

Use of the Beckmann reaction in the quinuclidon-3 series and interaction of the bicyclic ketone (VI) with hydrazoic acid under Schmidt conditions gave rise to a new type of 1-azabicyclic system derivatives of 1,4-diazabicyclo-(3,2,2)-nonane (XLIV) [117-119]. 

---