Functional Groups at Concave Sites: Asymmetric Diels‐Alder Synthesis with Almost Complete (Lewis‐Acid Catalyzed) or High (Uncatalyzed) Stereoselectivity

Regioselective Short Synthesis of Epiisoborneol Neopentyl Ether as Chiral Auxiliary: An Absolute Configuration Reset

“…15 Plietker and Neisius do not comment at all on the origin of their exo-stereoselectivity. [87] It is noteworthy that C(3) is distant by 2.5 Å from either C(5), or C(7), as well as 2.9 Å from C (8). The trajectory of the incoming reagent is quite important, as the Bürgi-Dunitz angle for hydride reduction of a carbonyl is ca.…”

“…[7] Using this latter concept for anthracene catalyzed cycloadditions to an isoborneol derived fumarate, see Ref. [8]. 2 Furthermore, the vast chemistry of camphor had previously been extensively explored, and thus was allowing various skeleton modifications and functionalizations.…”

“…The present main author thus embarked upon this synthesis. 3 Choosing the most direct access, [8] (1R)-camphor ((+)-1) was oxidized to (1R)-camphorquinone ((À )-2) in 90 % yield, 4 followed by stereoselective either reduction (LiAlH 4 , 82-96 % yield [37][38][39] ) or hydrogenation (H 2 , Raney-Ni, 70 % yield [37,40,41] ) to bis-exo-diol (À )-3 5 (Scheme 1). Deprotonation with NaH in DMF, and addition of neopentyl bromide at 100 °C, afforded a 45 : 55 mixture of regioisomers (À )-4 and (À )-5, separated by column chromatography in 35 and 40 % yield respectively.…”

“…50 % H 2 SO 4 , 60 °C, 94 % yield, [45] ) to the corresponding 3exo-neopentyloxy epicamphor (À )-9, prior to the ultimate stereoselective reduction to the desired epiisoborneol derivative (À )-4 (NaBH 4 , MeOH, 0 °C, 80 % yield, [45,46] ). 7 In several chemical transformations, its counterpart (À )-5 was found slightly superior, 8 and fifteen years later, this motivated Pericàs and Riera et al to report an even longer seven step regioselective synthesis (Scheme 3), [67] based on the tedious bisacetalization towards (+)-10, (ethylene glycol, TsOH, cyclohexane, 89 % yield after recycling the monoacetals (+)-6, [17,21,68,69] ). In their case, the key step was the sterically more accessible already known regioselective mono-deprotection to keto-acetal (À )-11 (4 M HCl, EtOH, reflux, 93 % yield, [68,69] ).…”

Acceleration and Deceleration Factors on the Hydrolysis Reaction of 4,6-O-Benzylidene Acetal Group

“…In general, T Δ S ⧧ becomes lower in the case that a substrate has structurally limited angles and space for access of reagents in order to get to the transition state. The concave face of the cis -fused system is generally less accessible. − The trans -fused systems of Glc and Man do not have convex and concave faces and then are easily accessed from both of up and down sides. Our data showed the slow hydrolysis of the benzylidene acetal group of nonacetylated Gal 3 along with lower T Δ S ⧧ , suggesting that the steric factor is likely to be involved in the entropy and disturbs protonation and hydration steps (Figure e, steps i, iii, and v). ,− …”