Ortho ester rearrangement

Claisen ortho ester rearrangement of propynyl alcohols of high enantiomeric purity gives the /S-allenylcarboxylic esters with diastereoselectivities of 90 10 up to 95 5110. 

Substiluled acrylic acids a-methylene-y-butyrolactones. The reaction of 1 with the allylic alcohol 2 at 170° gives the product (3) of Claisen ortho ester rearrangement. Oxidative elimination of GsHsSeOH gives the 2-substituted acrylic ester 4. 

The Johnson Ortho Ester Rearrangement 7.22.8 The Ireland Silyl Ester Enolate Rearrangement 722.9 Charge-accelerated Claisen Rearrangements 7.22.10 Cat ysis of Claisen Rearrangements 722.11 Competitive Rearrangements... 

C-IS in 55% yield (Scheme 53). In this case, the thermal Claisen rearrangement occurred stereospecifi-cally from the a-face of the bicycle, presumably via chair transition state (309) (Scheme 54). Therefore it was concluded that the ortho ester rearrangement occurred predominantly via boat transition state (310), providing the first example of a difference in transition state geometry observed in Claisen variants with the same substrate. 

Claisen ortho-ester rearrangement of indol-3-yl-alkanols introduces the migrating group to the indole 2-position " ... 

In comparison to ortho ester rearrangements, substitution of the C-l methylene group in the pericyclic system by sulfur results in a decrease of the stereoselectivity caused by a distortion of the six-membered ring in the transition state, but the effects are small. 

The homochiral acetylenic alcohol 2 [derived from ( )-4-benzyloxy-2-butenol by asymmetric Sharpless epoxidation via 2 in four steps] is transformed either to ( )-3 by treatment w ith lithium aluminum hydride or to (Z)-4 by hydrogenation with Lindlar catalyst. Simple Claisen or ortho ester rearrangement yield the same, but enantiomeric, products 5 and 6 with 85-90% ee288. 

In 5,6 rearrangements with only the double bond of the allylic moiety as part of a ring, chirality is transferred from an acyclic side chain to the ring system. Complete chirality transfer is observed in the ortho ester rearrangement of (R)-alcohol 1, obtained in optically active form by microbiological reduction, to (R)-ester 2393. 

A double ortho ester rearrangement of diol 16 leads to diester 17 together with a byproduct 18408. 

Ortho ester rearrangements also lack control over vinyl double-bond geometry. As a consequence, the reactions proceed without internal asymmetric induction yielding mixtures of diastereomers. Therefore, stereoselective syntheses by the ortho ester variant are often useful only in those cases in which the stereocenter that cannot" be controlled is destroyed in a following step. 

It is possible to control the internal asymmetric induction (simple diastereoselectivity) in ortho ester rearrangements by using special substitution patterns in the substrate. Thus, starting materials obtained from allylic alcohols 6 with a C-5 substituent R2 preferentially yield syn-diastereomers 7 due to 1,3-diaxial interactions of the substituents R2 and R3, which disfavor the transition state B, The necessity of a C-5 substituent for achieving diastereocontrol in ortho ester rearrangements is shown in Table 7, entry 1 in comparison to entry 3455. 

Table 7. Ortho Ester Rearrangements of Substituted Allylic Alcohols89...

Trimethyl 3-(phenylseleno)orthopropanoate 41 is utilized as an intermediate in the preparation of a-methylene-y-butyrolactones 42 via Claisen ortho ester rearrangement with allylic alcohols followed by oxidative elimination of phenylselenol233. 

Both the allyl vinyl ether, as well as the ortho ester rearrangement of allylic alcohol 14, give rise to the formation of a single diastereomer 16 or 18633. New bond formation occurs from the side opposite to the isopropyl group. 

Investigations of the stereochemical course of the ortho ester rearrangement of ynols 12a-g show that the yn-diastereomers673 13 are formed preferentially. The diastereoselectivity increases with the steric bulk of the alkyl substituents674. 

The concept of enantioconvergent synthesis has heretofore been virtually restricted to cases in which the chiral center is directly epimerizable such as in a-amino acids. In an alternative view, the separate transformation of two enantiomers via stereochemical 1y complementary pathways into a single enantiomeric series represents a case of enantioconvergence.(D For example, conversion of the enantiomeric alcohols la and lb to Ic via the Z and olefins respectively converge to the same enantiomer of the product derived via a Claisen ortho ester rearrangement (equation 1). (, 3)... 

Ortho ester rearrangement of allylic alkynyl alcohols. The allylic alkynyl alcohols (1) and (4) undergo stereoselective ortho ester Claisen rearrangement when refluxed with triethyl orthoacetate (propionic acid catalysis). In both cases... 

Dehydrosecodine (97) is believed to be a key intermediate in the biosynthesis of the Aspidosperma and Iboga alkaloids. The dihydro-derivative, secodine (102), has now been synthesized by a route involving a Claisen ortho ester rearrangement [(98) + (99) (100)] and in situ elimination of methanol [(100) - ... 

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