Experiments Directed Towards the Synthesis of Anthracyclinones. XXXIV Hetero-Diels - Alder Reactions Using Chiral Boron and Titanium Reagents

Abstract

Reactions between benzaldehyde or o-anisaldehyde and a series of silyloxy dienes catalysed by the chiral acyl- oxyborane (CAB) complex (4) give high yields of enantioselective products from a Mukaiyama aldol rather than a hetero-Diels–Alder reaction. Attempts to effect a similar catalytic reaction with anthraquinone aldehydes were unsuccessful but use of 2 equiv. of the CAB complex (1) followed by cyclization promotes a formal hetero- Diels–Alder reaction between the aldehyde (7) and the diene (12) to give the dihydropyrone (24) in 45% yield and with a 79% e.e. in favour of the 2'R enantiomer. Hetero-Diels–Alder reactions between the aldehyde (7) and the diene (12) using the chiral titanium complexes Ti[(R)-BINOL]Cl 2 , Ti[(R,R)-TADDOL]Cl 2 and Ti[(R)-BINOL] 2 have been investigated. The first two complexes promote the reaction at −30 and −78° respectively but with low induced enantioselectivities.

A New Reaction System for Horner-Wadsworth-Emmons Olefination of Optically Active 4-Hydroxy-2-oxo-alkylphosphonates and 4-Hydroxy-1-chloro-2-oxo-alkylphosphonates with Aliphatic Aldehydes

“…b¢-Hydroxy-a,b-unsatuarated ketones (I, Figure 1) are structure units that are frequently found in the molecule of natural products, such as pentamycin, 1 yashabushitriol, 2 and 1a, 25-dihydrovitamin D 3 3 etc. For the preparation of those compounds, several synthetic routes were reported in the literature including Mukaiyama aldol reaction, 4 LnCl 3 -mediated a¢-alkylations of enone and aldehydes, 5 reductive transformation of a,b-epoxy ketones to b-hydroxy ketones promoted through a photoinduced electron transfer process with 1,3-dimethyl-2-phenylbenzimidazoline (DMPBI), 6 vanadium-catalyzed aldol additions of allenic alcohols and aldehydes, 7 boron trifluoride-promoted reaction of dithio-substituted allylic anions and cyclic ethers, 8 and the reaction of a,b-unsaturated and a-phenyl acetals with expoxides promoted by lithium-potassium mixed base LICKOR [butylithium and potassium butoxide (so called 'Schlosser reagent')]. 9 The disadvantages of the above synthetic routes are significant, consisting of harsh reaction conditions, expensive reagents, low chemical yields and even low optical purity.…”

“…9 The disadvantages of the above synthetic routes are significant, consisting of harsh reaction conditions, expensive reagents, low chemical yields and even low optical purity. [4][5][6][7][8][9] Development of a new procedure leading to the preparation of the b¢-hydroxy-a,b-unsaturated ketones (I) seems necessary. It is reasonable to predict that the Horner-Wadsworth-Emmons (HWE) reaction will offer better results, since this method is usually applied under mild conditions.…”

“…IR (neat): 3447, 2964IR (neat): 3447, , 2934IR (neat): 3447, , 2877IR (neat): 3447, , 1663IR (neat): 3447, , 1627IR (neat): 3447, , 1464IR (neat): 3447, , 1380IR (neat): 3447, , 1186IR (neat): 3447, , 1114, 978 cm -1 . 1 H NMR (300 MHz, CDCl 3 ): d = 6.88 (dt, 1 H, J = 6.9, 16.2 Hz, COCH=CHCH 2 ), 6.10 (dt, 1 H, J = 1.5, 15.9 Hz, COCH=CHCH 2 ), 4.04-3.95 (m, 1 H, COCH 2 CHOH), 3.32 (m, 1 H, OH), 2.77 (dd, 1 H, J = 3.0, 17 4. Hz, COCH 2 CHOH), 2.62 (dd, 1 H, J = 9.6, 17.4 Hz, COCH 2 CHOH), 2.26-2.18 (m, 2 H, CH=CHCH 2 CH 2 ), 1.61-1.43 (m, 4 H, CH=CHCH 2 CH 2 CH 3 , CH 3 CH 2 CHOH), 1.00-0.92 (m, 6 H, CH=CHCH 2 CH 3 , CH=CHCH 2 CH 2 CH 3 ).…”