Ketones bicyclic, diastereoselective reactions

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

The reaction of the enamines of cyclohexanones with a,ft-unsaluraled sulfones gives mixtures resulting from attack of the enamine at the a- and /(-carbons of the oc,/ -unsaturated sulfone. The ratio of x- and /1-adducts is dependent upon the reaction solvent, the geometry and structure of the sulfone1 4. The diastereoselectivity of these reactions is also poor. The reaction of lithium enolates of cyclic ketones with ( )-[2-(methylsulfonyl)ethenyl]benzene, however, gives bicyclic alcohols, as single diastereomers, that result from initial -attack on the oc,/ -unsaturated sulfone5. 

The ketone 73 was reduced chemo- and diastereoselectively and protected to provide the silyl ether 74. The ester function was then deprotonated to the corresponding ester enolate (75) that was alkylated with methyl iodide exclusively from the Re face of the enolate to afford the bicycle 76 (Scheme 11). The substrate for the retro-aldol reaction (77) was prepared by a sequence that consists of seven functional and protecting group transformations. The retro-aldol reaction converted the bicyclic yS-hydroxy ketone 77 into the 1,3-diketone 69 via the alkoxide (78) in very good yield. 

Other cyclic or bicyclic ketones do not have a convex side but only a less concave and a more concave side. Thus, a hydride donor can add to such a carbonyl group only from a concave side. Because of the steric hindrance, this normally results in a decrease in the reactivity. However, the addition of this hydride donor is still less disfavored when it takes place from the less concave (i.e., the less hindered) side. As shown in Figure 10.10 (top) by means of the comparison of two reductions of norbomanone, this effect is more noticeable for a bulky hydride donor such as L-Selectride than for a small hydride donor such as NaBH4. As can be seen from Figure 10.10 (bottom), the additions of all hydride donors to the norbomanone derivative B (camphor) take place with the opposite diastereoselectivity. As indicated for each substrate, the common selectivity-determining factor remains the principle that the reaction with hydride takes place preferentially from the less hindered side of the molecule. 

In earlier studies, we reported remarkable rate and diastereoselectivity enhancements in allyl- and crotylborations involving a-hydroxyketones,6 a-oxocarboxylic acids7 and fi-hydroxyaldehydes and ketones, We now wish to report that fi-allyldiisopropoxyborane reacts with (3-ketoacids to produce tertiary homoallylic 13-hydroxycarboxylic acids. The reaction presumably proceeds through a bicyclic transition state (Scheme 1) to yield the desired product in good yield (Table 1). 

The allylboration of a-oxocarboxylic acids, a-amino ketones and a- and //-hydroxy aldehydes and ketones has also been examined [119]. A representative example of the reaction of an a-oxocarboxylic acid with E- or Z-2-butenylboronates is shown in Scheme 10-72. Clearly, the carboxylic acid -substituents exert a significant effect on the regio- and diastereoselectivity of these reactions. The reactions are proposed to occur via the bicyclic transition structure shown. The reac-... 

It is remarkable that the two diastereomeric salts of the bisulfite adduct can be separated with phenylethylamine. After being liberated, the less stable bicycle is converted directly with excellent regio- and diastereoselectivity via an exo-bromonium ion [231] into the sUyl-protected bromohydrin. The tricyclic ketone is then generated with potassium t-butoxide the lability of this intermediate requires that it is used for the next reaction step as crude material. 

While the reductive aldol cyclization products of keto-enones were accompanied by significant amounts of 1,4-reduction products, use of a 1,3-dione as the coupling partner proved to be efficient in attenuating the conjugate reduction pathway. The dione moiety is a more reactive electrophile than are simple ketone moieties because of its inductive effects and relief of dipole-dipole interactions of the two carbonyls. The reaction of dione-containing substrates 552 under the standard reaction conditions led to the formation of bicyclic aldol products 553 with excellent diastereoselectivity (>95 5) without formation of the 1,4-reduction product in most cases (Scheme 2-90). Reactions of enal-ketones 552 were also studied. Under optimal reaction conditions, five- and six-membered ring products 553 were formed accompanied by a moderate quantity of the conjugate reduction products. Representative results are summarized in Table 2-12. 

Hashimoto has reported the enantioselective domino carbonyl yUde formation/l,3-dipolar cycloaddition reaction of a range of a-diazo ketones 185 with various aromatic aldehydes 92, promoted by the chiral Rh(II)-tetrakis[N-benzene-fused-phthaloyl-(S)-valinate] complex (184). The present reaction afforded the corresponding bicyclic cycloadducts 186 in good yields and enantioselectivities. The exo diastereomer 186 was diastereoselectively generated as a single product in almost all the cases (Scheme 11.40) [61]. 

The utility of this method also stems from the fact that the nitro group enables C—C bond formation prior to the rearrangement. Michael addition of the anion derived from 276 to methyl vinyl ketone led to allylic nitro compound 277, which rearranged to allylic alcohol 278 in hi yield and excellent diastereoselectivity. Meanwhile, a single diastereomer of the bicyclic framework 280 was available under thermodynamic control from nitro aldehyde 279 via reversible Henry reaction, and transposition of the allylic nitro stereocenter to allylic alcohol 281 resulted from the suprafacial nature of the ensuing [2,3]-rearrangement. 

Dipolar cycloaddition reactions with stable and easily prepared azomethine imines, for the synthesis of a diverse array of heterocycles, have attracted considerable attention [125]. The complex RhjldS-MPPlM) (47) catalyzes the highly diastereoselective [3-l-2-l-l]-cycloaddition reaction between a diazo ketone and azomethine imines [126]. The final products are multi-functionalized bicyclic pyrazolidinone derivatives isolated in moderate to high yields (Scheme 9.12). 

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